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Infection and Immunity, March 2001, p. 1477-1482, Vol. 69, No. 3
Department of Pathology, University of Utah
School of Medicine, Salt Lake City, Utah1;
Department of Microbiology and Immunology, Uniformed Services
University of the Health Sciences, Bethesda,
Maryland2; Department of Microbiology,
University of Alabama
Received 14 November 2000/Accepted 7 December 2000
Lipopolysaccharide (LPS) derived from the periodontal pathogen
Porphyromonas gingivalis has been reported to differ
structurally and functionally from enterobacterial LPS. These studies
demonstrate that in contrast to protein-free enterobacterial LPS, a
similarly purified preparation of P. gingivalis LPS
exhibited potent Toll-like receptor 2 (TLR2), rather than TLR4, agonist
activity to elicit gene expression and cytokine secretion in murine
macrophages and transfectants. More importantly, TLR2 stimulation by
this P. gingivalis LPS preparation resulted in differential
expression of a panel of genes that are normally induced in murine
macrophages by Escherichia coli LPS. These data suggest
that (i) P. gingivalis LPS does not signal through TLR4 and
(ii) signaling through TLR2 and through TLR4 differs quantitatively and
qualitatively. Our data support the hypothesis that the shared
signaling pathways elicited by TLR2 and by TLR4 agonists must diverge
in order to account for the distinct patterns of inflammatory gene expression.
Lipopolysaccharides (LPS) are among
the most potent inflammatory bacterial mediators and have been strongly
implicated in the inflammatory response associated with gram-negative
sepsis. Most LPS signaling studies have used LPS preparations derived from species within the Enterobacteriaceae, which possess
relatively well-conserved lipid A structures (reviewed in reference
36). A convergence of data suggest that these prototypic
LPS preparations, when highly purified, elicit LPS responses that are
restricted in the use of TLR4 as the principal signal-transducing
molecule (reviewed in reference 21), which is strongly
supported by the finding that synthetic E. coli lipid A
activated Toll-like receptor 4 (TLR4) and not TLR2 transfectants
(8). However, the lipid A of nonenterobacterial species,
e.g., Porphyromonas gingivalis, which has been implicated in
the inflammation associated with chronic periodontitis (reviewed in
reference 9), differs both structurally and functionally
from enterobacterial lipid A. Specifically, the major species of
P. gingivalis lipid A is composed of unique branched fatty
acids, with longer carbon chains than in enterobacterial lipid A, the
absence of a phosphoryl group at position 4' of the nonreducing
glucosamine, as well as other modifications (Fig. 1) (1). Consistent with
these structural differences is the finding that P. gingivalis LPS activity is poorly inhibited by polymyxin B
(12), which has been postulated to inactivate LPS by
binding electrostatically to negatively charged phosphate groups, leading to a subsequent interaction of polymyxin B with the hydrophobic fatty acids (25, 33). Although P. gingivalis-induced signaling was shown some time ago to be CD14
dependent (34), site-specific mutagenesis of CD14 suggests
that the substitution of certain charged amino acids differentially
affects the abilities of Escherichia coli and P. gingivalis LPS to bind CD14 (4, 5). In addition, binding of P. gingivalis LPS to LPS binding protein has been
reported to be 100-fold less than observed for E. coli LPS
(9). In vivo, P. gingivalis LPS has been
reported to be much less toxic than other LPS preparations (reviewed in
reference 27). P. gingivalis LPS has also been
shown to be active on C3H/HeJ macrophages (12, 32), which
possess a point mutation in tlr4 that precludes signaling by
enterobacterial LPS (24, 26). In contrast, Tabeta et al. (30) reported that human gingival fibroblasts exhibit a
slight increase above basal interleukin-6 (IL-6) production upon
stimulation with P. gingivalis LPS and that a monoclonal
antibody directed against human TLR4 reduced the IL-6 level below that
of the medium-treated cells. Differences in cytokine gene expression or
secretion by P. gingivalis LPS and enterobacterial LPS
preparations have also been reported for both myeloid and nonmyeloid
cell types (4, 11, 12, 32).
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.3.1477-1482.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Signaling by Toll-Like Receptor 2 and 4 Agonists
Results in Differential Gene Expression in Murine Macrophages
Birmingham, Birmingham,
Alabama3; and Department of Animal
Health and Biomedical Sciences, University of Wisconsin at Madison,
Madison, Wisconsin4
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
View larger version (17K):
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FIG. 1.
(A) Chemical structures of the major species of lipid A
produced by E. coli and P. gingivalis. The major
structural differences include the nature and number of fatty acids,
presence or absence of the second phosphate in position 4', and
substitution of the position 1 phosphate. A more extensive and detailed
comparison is presented in reference 36.
Having purified P. gingivalis LPS by the same protocol as used to demonstrate the restricted usage of TLR4 by enterobacterial LPS to mediate signaling (8), we demonstrate herein that a preparation of P. gingivalis LPS utilizes TLR2, not TLR4, to mediate inflammatory signaling. In addition, P. gingivalis LPS differentially activates a panel of genes relative to E. coli LPS, suggesting that TLR2- and TLR4-mediated signaling pathways diverge.
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MATERIALS AND METHODS |
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Abstract
Introduction
Materials and Methods
Results and Discussion
References
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Mice. C3H/OuJ and C3H/HeJ mice were purchased from the Jackson Laboratory, (Bar Harbor, Maine). Thioglycolate-elicited peritoneal exudate macrophages were cultured as described previously (29).
LPS preparations.
E. coli K235 LPS was prepared by a
modification of the phenol water extraction method of McIntire et al.
(20) (<0.008% protein). E. coli J5 (Rc) LPS
was purchased from List Biological Laboratories (Campbell, Calif.) and
was subjected to phenol reextraction (repurified) by a method that
results in the elimination of contaminants that are active on C3H/HeJ
macrophages (17, 19). This reextraction method, detailed
more recently by Hirschfeld et al. (8), results in
enterobacterial LPS preparations that utilize TLR4, and not TLR2, for
signaling. Briefly, 5 mg of Rc LPS was resuspended in 1 ml of room
temperature, endotoxin-free water containing 0.2% triethylamine (TEA).
The sample was split into two 500-µl aliquots, and one aliquot was
stored at 4°C without further manipulation (unpurified LPS).
Deoxycholate was added to the remaining aliquot to a final
concentration of 0.5%, followed by the addition of 500 µl of
water-saturated phenol. The sample was vortexed intermittently for 5 min, and the phases were allowed to separate at room temperature for 5 min. The sample was placed on ice for 5 min and then centrifuged at
4°C for 2 min at 10,000 × g. The top aqueous layer
was transferred to a new tube, and the phenol phase was subjected to
reextraction with 500 µl of 0.2% TEA-0.5% deoxycholate. The
aqueous phases were pooled and reextracted with 1 ml of water-saturated
phenol. The pooled aqueous phases were adjusted to 75% ethanol and 30 mM sodium acetate and were allowed to precipitate at 
20°C for 1 h. The precipitate was centrifuged at 4°C for 10 min at
10,000 × g, washed in 1 ml of cold 100% ethanol, and
air dried. The precipitate was resuspended in the original volume (500 µl) of 0.2% TEA. One hundred percent recovery was assumed for the
purified LPS sample (19), which will be referred to as
purified LPS. P. gingivalis 33277 LPS was purified by two
rounds of hot phenol extraction (22), followed by phenol
reextraction (8, 17, 19). Colloidal gold staining was
carried out using a kit (Enhanced Colloidal Gold; Bio-Rad, Hercules,
Calif.), which has a lower limit of sensitivity of 10 to 100 pg
protein. Twenty micrograms of P. gingivalis LPS was analyzed
by thin-layer chromatography (TLC) using silica gel H plates, developed
with chloroform-methanol-water-ammonium hydroxide (50:25:4:2). The
plate was sprayed with dichromate solution and charred. Most of the LPS
chromatographed at the origin. When the LPS was acid hydrolyzed (0.1 N
HCl at 100°C for 25 min) and analyzed by TLC, most of the lipid A
migrated off the origin, consistent with an LPS preparation that is
>95% pure.
Isolation of total cellular RNA and RT-PCR.
All procedures
for detection of cytokine and chemokine mRNA by semiquantitative RT-PCR
have been detailed previously (18, 28). Briefly, total
cellular RNA was extracted from macrophage cultures and was reverse
transcribed. PCR amplifications were performed on the resultant cDNA
for the gene of interest, using specific sense and antisense primers
for cytokine mRNA, i.e., IL-1
(35 cycles), tumor necrosis factor
alpha (TNF-
) (31 cycles), IL-6 (30 cycles), gamma interferon
(IFN-
) (35 cycles), IL-12 p35 (31 cycles), IL-12 p40 (22 cycles),
and for chemokine mRNA, i.e., MIP-1 (27 cycles), MIP-2 (26 cycles),
IP-10 (30 cycles), JE (32 cycles), and MCP-5 (29 cycles). The gene
encoding hypoxanthine-guanine phosphoribosyltransferase
(HPRT) (24 cycles) was included as a housekeeping gene to
control for differences in cDNA for each treatment during the
amplification reaction. PCR amplification products were electrophoresed
on a 1% agarose gel and blotted overnight onto a Nytran membrane. The
DNA was then UV cross-linked onto the membrane and baked at 80°C for
2 h. The amplified PCR products were detected by Southern blot
analysis using gene-specific oligonucleotide probes labeled with the
Amersham 3-oligolabeling and detection systems (Amersham International,
Buckinghamshire, England).
Cell lines and transfections.
The human astrocytoma cell
lines U87 and U373, were obtained from the American Type Culture
Collection (Manassas, Va.). The subclone of the human embryonic kidney
epithelial cell line HEK 293 and the constructs for FLAG-tagged human
TLR1, TLR2, TLR3, and TLR4, pFLAG control vector, the ELAM-1 luciferase
reporter construct, and Rous sarcoma virus--galactosidase
(RSV--Gal) were provided by Tularik (South San Francisco, Calif.)
(13). Conditions for transfection of cells have been
detailed elsewhere (7, 8). Briefly, 293 cells were
cotransfected in six-well plates using a calcium phosphate kit
(Clontech, Palo Alto, Calif.) with 2, 0.5, and 0.5 µg of the TLR
expression construct, the ELAM-1 luciferase reporter construct, and the
RSV--Gal construct, respectively, to normalize for transfection
efficiency. Cells were grown for 36 h and stimulated with the
indicated agonist for an additional 6 h. U87 cells were
transfected in 12-well plates using pFx-2 (Invitrogen, Carlsbad,
Calif.) with 2 µg of either TLR2 or TLR4 expression construct. Cells
were then grown for 24 h in Dulbecco modified Eagle medium (DMEM)
with Nutridoma-HU (Boehringer Mannheim, Indianapolis, Ind.) followed by
stimulation with agonist for an additional 24 h in
DMEM-Nutridoma-HU containing 2% human serum. U373 cells were grown in
24-well plates for 24 h in DMEM with Nutridoma-HU followed by
stimulation with agonist for an additional 24 h in
DMEM-Nutridoma-HU containing 2% human serum.
Luciferase and cytokine assays.
IL-6 (U87 and U373 cells)
and IL-8 (HEK 293) levels were measured by enzyme-linked immunosorbent
assay (ELISA; Endogen, Woburn, Mass.). ELISAs specific for total and
bioactive murine IL-12 have been detailed elsewhere (29).
Murine TNF- was also measured by ELISA (Genzyme, Cambridge, Mass.).
To assay for NF-
B-dependent luciferase activity, transfected 293 cells were lysed using reporter lysis buffer (Promega, Madison, Wis.),
and 20 µl of lysate was assayed for both luciferase and
-galactosidase activities using a Dynatec MLX luminometer after
incubation in luciferase assay reagent (Promega) and Galacto-Light with
light emission accelerator (Tropix, Bedford, Mass.), respectively.
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RESULTS AND DISCUSSION |
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Top
Abstract
Introduction
Materials and Methods
Results and Discussion
References
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Previous reports that P. gingivalis LPS (i) activates
C3H/HeJ macrophages, (ii) differs from enterobacterial LPS in its
capacity to elicit a variety of responses, and (iii) possesses a lipid A with a markedly distinct structure led us to evaluate this LPS further upon hot phenol water extraction (22), followed by
repurification using a method demonstrated to eliminate TLR2-dependent
ligands from several enterobacterial LPS preparations (8).
The preparation of P. gingivalis LPS used in this study was
confirmed to be essentially protein free, as evidenced by a lack of
detectable bands in colloidal gold-stained blots of 10 µg of P. gingivalis LPS preparation (Fig. 2);
i.e., the protein concentration of this preparation is <100 pg of
protein/10 µg of LPS, or <0.001%, in contrast to 5 µg of the
commercial E. coli Rc LPS, which contained clearly
detectable protein bands that were eliminated by repurification. Figure
3 illustrates that under conditions where
protein-free E. coli K235 LPS completely discriminates
between LPS-normoresponsive C3H/OuJ and TLR4-defective C3H/HeJ
macrophages with respect to induction of IL-1 and MIP-2 mRNA,
P. gingivalis LPS elicits very comparable levels of
dose-dependent induction of both genes in macrophages from both
strains. Thus, these data confirm previous evidence supporting the
hypothesis that stimulation of murine macrophages with P. gingivalis LPS is TLR4 independent (12, 32).
Moreover, the potency of the E. coli LPS is clearly greater
than that of the P. gingivalis LPS, as evidenced by a clear
diminution of signal in those samples stimulated by P. gingivalis versus E. coli LPS at 1 ng/ml.
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Using 100 ng/ml, a concentration that was superoptimal for induction of
expression of both IL-1 and MIP-2 genes by both LPS preparations, we
carried out a kinetic analysis and compared induction of 11 cytokine
genes in C3H/OuJ macrophages (Fig. 4).
Induction of IL-1 and MIP-1 mRNA expression was quite comparable
over the time course examined. A second subset of genes, i.e., TNF-, MIP-2, IP-10, and IL-12 p35, were inducible by the P. gingivalis LPS preparation, but steady-state mRNA levels declined
more rapidly than when cells were stimulated with E. coli
LPS. Induction of JE and IL-6 mRNA was poor and steady-state levels
declined rapidly, while IFN-, IL-12 p40, and MCP-5 gene expression
was strongly induced by E. coli LPS but not by P. gingivalis LPS. Even at a dose of 1 µg/ml, the P. gingivalis preparation induced MCP-5 only minimally (data not
shown). Secretion of TNF-, total IL-12 (IL-12 p40 plus IL-12 p70),
and bioactive IL-12 (IL-12 p70) was markedly attenuated in P. gingivalis- versus E. coli-stimulated cultures (Table
1). Therefore, not only is the P. gingivalis-induced gene expression TLR4 independent, but also such
differential gene expression and cytokine secretion implies that there
must be qualitative differences in signaling between TLR2 and TLR4.
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We recently demonstrated that the apparent TLR2 dependency of many LPS
preparations is eliminated by phenol reextraction, while TLR4
dependency is retained (8, 17, 19). In contrast, our
P. gingivalis preparation, which was confirmed to be
equivalently protein free and exhibited an electrophoretic mobility in
TLC consistent with LPS, did not appear to stimulate gene expression through TLR4 since IL-1 and MIP-2 genes were expressed in very comparable, dose-dependent fashions in both normal and TLR4-defective macrophages (Fig. 3). Therefore, to confirm the TLR4 independence of
the P. gingivalis LPS preparation, the U87 astrocytoma cell line was transiently transfected with either human TLR4 or TLR2 constructs and then stimulated with either E. coli Rc LPS
(as purchased or repurified) or the P. gingivalis LPS
preparation, repurified identically to the E. coli Rc
preparation. Figure 5 illustrates that
the P. gingivalis LPS induces IL-6 production in U87 cells
that overexpress TLR2 (Fig. 5A) but not TLR4 (Fig. 5B). As recently
reported (8), the commercially prepared and repurified
E. coli Rc preparations both stimulated TLR4 transfectants, but only the unpurified preparation was active in TLR2 transfectants. These findings were confirmed using a similar astrocytoma cell line,
U373, that has been reported to be responsive to E. coli LPS
but not to bacterial lipoproteins and to express endogenous TLR4 but
not TLR2 mRNA (7). U373 cells secreted IL-6 in response to
unpurified or purified E. coli Rc LPS but not in response to the P. gingivalis LPS preparation (Fig. 5C). TLR2
transfection of HEK 293 cells also conferred sensitivity to P. gingivalis LPS, as measured by ELAM-1 luciferase reporter gene
expression or IL-8 secretion (Fig. 6),
with a dose dependency that closely parallels that seen in the primary
macrophages (Fig. 3). In contrast to the P. gingivalis
sensitivity conferred upon HEK 293 cells by TLR2 overexpression,
transfection with a pFLAG control vector or a TLR1, TLR3, or TLR4
construct failed to render 293 cells sensitive to P. gingivalis LPS (data not shown). Finally, Chinese hamster ovary
(CHO) cells engineered to express an ELAM.Tac (CD25) reporter construct
and CD14 only (14, 15) failed to respond to this same
preparation of P. gingivalis LPS or to the synthetic TLR2
agonist, tripalmitoyl-S-glycerylcysteine-modified Ser
Lys4 peptide, but did respond to E. coli lipid
A, presumably via endogenous hamster TLR4. In contrast, CHO cells
engineered to express the reporter construct, CD14, and human TLR2
(14, 15) responded to all three stimuli to express Tac
antigen (H. Heine, personal communication). Thus, in four separate cell
lines (transiently or stably transfected) and in primary macrophages,
where functional TLR2 and TLR4 expression levels differ, this P. gingivalis LPS preparation initiates intracellular signaling
through TLR2, while E. coli LPS selectively utilizes TLR4.
That our preparation of P. gingivalis LPS signals via TLR2
is also consistent with two previous reports that Rhodobacter
sphaeroides lipid A, which blocks E. coli LPS-induced
signaling in a TLR4-dependent fashion (15), fails to block
P. gingivalis LPS-induced TNF production (1, 12).
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Our data extend significantly previous observations indicating that
P. gingivalis LPS activates macrophages differently from enterobacterial LPS preparations. Clearly, the data presented herein
indicate that P. gingivalis LPS does not signal through TLR4, likely accounting for the comparability of induction of IL-1
and MIP-2 mRNA in C3H/OuJ and C3H/HeJ macrophages (Fig. 3). However, we
cannot be certain that the TLR2 stimulatory activity detected in the
P. gingivalis LPS preparation is attributable to the LPS,
despite the fact that the LPS represents the predominant species
(>95%). It is possible that a minor contaminant contained within the
P. gingivalis LPS preparation is responsible for the TLR2
agonist activity of this preparation. Future experiments using
synthetic P. gingivalis lipid A will be required to confirm whether or not P. gingivalis LPS is the true TLR2 agonist.
Faure et al. (6) reported recently that human dermal microvessel or umbilical vein endothelial cells express predominantly TLR4 but very weakly TLR2 and respond vigorously to E. coli LPS but not to Mycobacterium tuberculosis 19-kDa lipoprotein, a TLR2 ligand. Thus, the earlier observation of Cunningham et al. (4) that human endothelial cells responded to produce E-selectin upon stimulation with E. coli but not P. gingivalis LPS are likely explained by our observation that P. gingivalis requires TLR2, and not TLR4, for activation. However, Cunningham et al. (4) also demonstrated that P. gingivalis LPS blocked E. coli LPS-induced E-selectin expression in human umbilical vein endothelial cell cultures in a CD14-independent fashion. Thus, it is possible that P. gingivalis LPS, like R. sphaeroides LPS, is an inactive antagonist of E. coli LPS at the level of TLR4. A second possible mechanism for this inhibition is that engagement of TLR2 by the agonist contained within the P. gingivalis LPS preparation sequesters or exhausts shared signaling molecules (MyD88, etc.) such that subsequent stimulation by E. coli LPS through TLR4 is precluded.
The finding of diminished potency of P. gingivalis versus
E. coli LPS for the induction of IL-1 and MIP-2 in
C3H/OuJ macrophages (Fig. 3), coupled with differential gene expression
(Fig. 4), implies that signaling pathways through TLR2 and TLR4 are
quantitatively and/or qualitatively different. One possibility is that
the utilization of TLR2 rather than TLR4 results in a more limited
capacity to generate intracellular signals required for the expression
of certain genes, either through differences related to the strength of
signaling through TLR2 versus TLR4 or, perhaps secondarily, through the
difference in capacity of TLR2 and TLR4 to recruit additional signaling
molecules to the LPS signaling complex. In this regard, it is possible
that TLR2 interacts with other TLRs to elicit signaling by our P. gingivalis preparation, as has been recently observed for
signaling by Neisseria meningitidis (35). Different affinities of P. gingivalis LPS and
enterobacterial LPS for CD14 (5) could also alter the
interaction of CD14, once engaged by a particular LPS, with specific
TLRs. Regardless of the mechanism, there appears to be a divergence of
signaling pathways that results in differential gene expression distal
to or distinct from the engagement of shared upstream signaling
molecules. This conclusion is also strengthened by our recent
observation that another TLR2 agonist, soluble tuberculosis factor
(kindly provided by Matthew Fenton) (21), induces IL-1
but not MCP-5 mRNA (V. Toshchakov, unpublished observations).
It is tempting to speculate that the mitigated toxicity of P. gingivalis compared with that of enterobacterial LPS preparations in vivo is secondary to mitigated production of cytokines that have
been implicated in endotoxicity (e.g., TNF-, IL-12, and IFN-
[reviewed in reference 29). While P. gingivalis can invade epithelial cells and replicate
intracellularly (14), the failure of this P. gingivalis LPS preparation to induce IL-12 and IFN- mRNA may
also contribute to the chronicity of this agent in the pathogenicity of
periodontitis, since IL-12 and IFN- are necessary for the
elimination of many intracellular pathogens, such as
Mycobacterium and Listeria species
(10). Other bacterial pathogens that produce potent
proinflammatory molecules that act through TLR2 but not TLR4 have been
identified. These include Borrelia burgdorferi, the agent of
Lyme disease, which causes a chronic infection in mice and humans
characterized by inflammatory arthritis and produces numerous distinct
tripalmitoyl-S-glycerylcysteine-bearing lipoproteins that
are TLR2 ligands (2, 3, 7, 16). Several
Mycoplasma species, which are also associated with chronic
infections and arthritis, produce extremely potent diacylated
lipoproteins that interact with TLR2 (23, 31). Although
both B. burgdorferi and Mycoplasma species cause
chronic diseases, chronicity cannot be attributed solely to signaling
through TLR2 since administration of high doses of purified
TLR2-dependent bacterial lipoproteins has been associated with acute,
toxic-type syndromes (37).
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ACKNOWLEDGMENTS |
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We thank Ulrich Zähringer, Research Center Borstel,
Borstel, Germany, for providing Fig. 1 and for helpful discussions
about differences in E. coli and P. gingivalis
lipid A structures. We also acknowledge Carsten J. Kirschning, Ralf
Schwandner, and Holger Wesche for providing the HEK 293 cells and
expression constructs of human TLRs, ELAM-1 luciferase, and
RSV--Gal. Finally, we thank Holger Heine for sharing unpublished
data on the activity of our P. gingivalis LPS preparation in
CHO cell transfectants.
This work was supported by NIH grants AI-32223 (J.J.W.) and 5P30-CA-42014 (University of Utah Core facilities), DE-08228 (S.M.M.), GM-50870 (N.Q.), and AI-18797 (S.N.V.), and USUHS protocol R07338 (S.N.V.).
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FOOTNOTES |
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* Corresponding author. Mailing address: Department of Microbiology and Immunology, USUHS, 4301 Jones Bridge Road, Bethesda, MD 20814. Phone: (301) 295-3446. Fax: (301) 295-1545. E-mail: vogel{at}bob.usuhs.mil.
Editor: R. N. Moore
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REFERENCES |
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Abstract
Introduction
Materials and Methods
Results and Discussion
References
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| 1. | Aida, Y., K. Kusumoto, K. Nakatomi, H. Takada, M. J. Pabst, and K. Maeda. 1995. An analogue of lipid A and LPS from Rhodobacter sphaeroides inhibits neutrophil responses to LPS by blocking receptor recognition of LPS and by depleting LPS-binding protein in plasma. J. Leukoc. Biol. 58:675-682[Abstract]. |
| 2. |
Aliprantis, A. O.,
R. B. Yang,
M. R. Mark,
S. Suggett,
B. Devaux,
J. D. Radolf,
G. R. Klimpel,
P. Godowski, and A. Zychlinsky.
1999.
Cell activation and apoptosis by bacterial lipoproteins through Toll-like receptor-2.
Science
285:736-739 |
| 3. |
Brightbill, H. D.,
D. H. Libraty,
S. R. Krutzik,
R. B. Yang,
J. T. Belisle,
J. R. Bleharski,
M. Maitland,
M. V. Norgard,
S. E. Plevy,
S. T. Smale,
P. J. Brennan,
B. R. Bloom,
P. J. Godowski, and R. L. Modlin.
1999.
Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors.
Science
285:732-736 |
| 4. | Cunningham, M. D., J. Bajorath, J. E. Somerville, and R. P. Darveau. 1999. Escherichia coli and Porphyromonas gingivalis lipopolysaccharide interactions with CD14: implications for myeloid and nonmyeloid cell activation. Clin. Infect. Dis. 28:497-504[Medline]. |
| 5. |
Cunningham, M. D.,
R. A. Shapiro,
C. Seachord,
K. Ratcliffe,
L. Cassiano, and R. P. Darveau.
2000.
CD14 employs hydrophilic regions to "capture" lipopolysaccharides.
J. Immunol.
164:3255-3263 |
| 6. |
Faure, E.,
O. Equils,
P. A. Sieling,
L. Thomas,
F. X. Zhang,
C. J. Kirschning,
N. Polentarutti,
M. Muzio, and M. Arditi.
2000.
Bacterial lipopolysaccharide activates NF-kappaB through Toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells.
J. Biol. Chem.
275:11058-11063 |
| 7. |
Hirschfeld, M.,
C. J. Kirschning,
R. Schwandner,
H. Wesche,
J. H. Weis,
R. M. Wooten, and J. J. Weis.
1999.
Cutting edge: inflammatory signaling by Borrelia burgdorferi lipoproteins is mediated by Toll-like receptor 2.
J. Immunol.
163:2382-2386 |
| 8. |
Hirschfeld, M.,
Y. Ma,
J. H. Weis,
S. N. Vogel, and J. J. Weis.
2000.
Cutting edge: repurification of LPS eliminates signaling through both human and murine Toll-like receptor 2.
J. Immunol.
165:618-622 |
| 9. | Holt, S. C., L. Kesavalu, S. Walker, and C. A. Genco. 1999. Virulence factors of Porphyromonas gingivalis. Periodontol. 2000 20:168-238[Medline]. |
| 10. | Kaufmann, S. H. E. 1999. Immunity to intracellular bacteria, p. 1335-1371. In W. E. Paul (ed.), Fundamental immunology, 4th ed. Lippincott-Raven Publishers, Philadelphia, Pa. |
| 11. |
Kent, L. W.,
F. Rahemtulla,
R. D. Hockett,
R. C. Gilleland, and S. M. Michalek.
1998.
Effect of lipopolysaccharide and inflammatory cytokines on interleukin-6 production by healthy human gingival fibroblasts.
Infect. Immun.
66:608-614 |
| 12. |
Kirikae, T.,
T. Nitta,
F. Kirikae,
Y. Suda,
S. Kusumoto,
N. Qureshi, and M. Nakano.
1999.
Lipopolysaccharides (LPS) of oral black-pigmented bacteria induce tumor necrosis factor production by LPS-refractory C3H/HeJ macrophages in a way different from that of Salmonella LPS.
Infect. Immun.
67:1736-1742 |
| 13. |
Kirschning, C. J.,
H. Wesche,
T. M. Ayrers, and M. Rothe.
1998.
Human Toll-like receptor 2 confers responsiveness to bacterial lipipolysaccharide.
J. Exp. Med.
188:2091-2097 |
| 14. | Lamont, R. J., A. Chan, C. M. Belton, K. T. Izutsu, D. Vasel, and A. Weinberg. 1995. Porphyromonas gingivalis invasion of gingival epithelial cells. Infect. Immun. 63:3878-3885[Abstract]. |
| 15. | Lien, E., T. K. Means, H. Heine, A. Yoshimura, S. Kusumoto, K. Fukase, M. J. Fenton, M. Oikawa, N. Qureshi, B. Monks, R. W. Finberg, R. R. Ingalls, and D. T. Golenbock. 2000. Toll-like receptor 4 imparts ligand-specific recognition of bacterial lipopolysaccharide. J. Clin. Investig. 105:497-504[Medline]. |
| 16. |
Lien, E.,
T. J. Sellati,
A. Yoshimura,
T. H. Flo,
G. Rawadi,
R. W. Finberg,
J. D. Carroll,
T. Espevik,
R. R. Ingalls,
J. D. Radolf, and D. T. Golenbock.
1999.
Toll-like receptor 2 functions as a pattern recognition receptor for diverse bacterial products.
J. Biol. Chem.
274:33419-33425 |
| 17. | Manthey, C. L., P.-Y. Perera, B. E. Henricson, T. A. Hamilton, N. Qureshi, and S. N. Vogel. 1994. Endotoxin-induced early gene expression in C3H/HeJ (Lpsd) macrophages. J. Immunol. 153:2653-2663[Abstract]. |
| 18. | Manthey, C. L., P.-Y. Perera, C. A. Salkowski, and S. N. Vogel. 1994. Taxol provides a second signal for murine macrophage tumoricidal activity. J. Immunol. 152:825-831[Abstract]. |
| 19. | Manthey, C. L., and S. N. Vogel. 1994. Elimination of trace endotoxin protein from rough chemotype LPS. J. Endotoxin Res. 1:84-92. |
| 20. | McIntire, F. C., H. W. Sievert, G. H. Barlow, R. A. Finley, and A. Y. Lee. 1967. Chemical, physical, biological properties of a lipopolysaccharide from Escherichia coli K-235. Biochemistry 6:2363-2372[CrossRef][Medline]. |
| 21. |
Means, T. K.,
S. Wang,
E. Lien,
A. Yoshimura,
D. T. Golenbock, and M. J. Fenton.
1999.
Human Toll-like receptors mediate cellular activation by Mycobacterium tuberculosis.
J. Immunol.
163:3920-3927 |
| 22. |
Millar, S. J.,
E. G. Goldstein,
M. J. Levine, and E. Hausmann.
1986.
Modulation of bone metabolism by two chemically distinct lipopolysaccharide fractions from Bacteroides gingivalis.
Infect. Immun.
51:302-306 |
| 23. |
Muhlradt, P. F.,
M. kiess,
H. Meyer,
S. Sussmuth, and G. Jung.
1998.
Structure and specific activity of macrophage-stimulating lipopeptides from Mycoplasma hyorhinis.
Infect. Immun.
66:4804-4810 |
| 24. |
Poltorak, A.,
X. He,
I. Smirnova,
M. Y. Liu,
C. V. Huffel,
X. Du,
D. Birdwell,
E. Alejos,
M. Silva,
C. Galanos,
M. Freudenberg,
P. Ricciardi-Castagnoli,
B. Layton, and B. Beutler.
1998.
Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in the Tlr4 gene.
Science
282:2085-2088 |
| 25. | Pristovsek, P., and J. Kidric. 1999. Solution structure of polymyxins B and E and effect of binding to lipopolysaccharide: an NMR and molecular modeling study. J. Med. Chem. 42:4604-4613[CrossRef][Medline]. |
| 26. |
Qureshi, S. T.,
L. Lariviere,
G. Leveque,
S. Clermont,
K. J. Moore,
P. Gros, and D. Malo.
1999.
Endotoxin-tolerant mice have mutations in Toll-like receptor 4 (Tlr4).
J. Exp. Med.
189:615-625 |
| 27. | Roberts, F. A., G. J. Richardson, and S. M. Michalek. 1997. Effects of Porphyromonas gingivalis and Escherichia coli lipopolysaccharides on mononuclear phagocytes. Infect. Immun. 65:3248-3254[Abstract]. |
| 28. |
Salkowski, C. A.,
G. Detore,
A. Franks,
M. C. Falk, and S. N. Vogel.
1998.
Pulmonary and hepatic gene expression following cecal ligation and puncture: monophosphoryl lipid A prophylaxis attenuates sepsis-induced cytokine and chemokine expression and neutrophil infiltration.
Infect. Immun.
66:3569-3578 |
| 29. |
Salkowski, C. A.,
K. Kopydlowski,
J. Blanco,
M. J. Cody,
R. McNally, and S. N. Vogel.
1999.
IL-12 is dysregulated in macrophages from IRF-1 and IRF-2 knockout mice.
J. Immunol.
163:1529-1536 |
| 30. |
Tabeta, K.,
K. Yamazaki,
S. Akashi,
K. Miyake,
H. Kumada,
T. Umemoto, and H. Yoshie.
2000.
Toll-like receptors confer responsiveness to lipopolysaccharide from Porphyromonas gingivalis in human gingival fibroblasts.
Infect. Immun.
68:3731-3735 |
| 31. |
Takeuchi, O.,
A. Kaufmann,
K. Grote,
T. Kawai,
K. Hoshino,
M. Morr,
P. F. Mühlradt, and S. Akira.
2000.
Cutting edge: preferentially the R-stereoisomer of the mycoplasmal lipopeptide macrophage-activating lipopeptide-2 activates immune cells through a Toll-like receptor-2- and MyD88-dependent signaling pathway.
J. Immunol.
164:554-557 |
| 32. | Tanamoto, K., S. Azumi, Y. Haishima, H. Kumada, and T. Umemoto. 1997. The lipid A moiety of Porphyromonas gingivalis lipopolysaccharide specifically mediates the activation of C3H/HeJ mice. J. Immunol. 158:4430-4436[Abstract]. |
| 33. | Vaara, M., T. Vaara, M. Jensen, I. Helander, M. Nurminen, E. T. Rietschel, and P. H. Makela. 1981. Characterization of the lipopolysaccharide from the polymyxin-resistant pmrA mutants of Salmonella typhimurium. FEBS Lett. 129:145-149[CrossRef][Medline]. |
| 34. | Watanabe, A., A. Takeshita, S. Kitano, and S. Hanazawa. 1996. CD14-mediated signal pathway of Porphyromonas gingivalis lipopolysaccharide in human gingival fibroblasts. Infect. Immun. 64:4488-4494[Abstract]. |
| 35. |
Wyllie, D. H.,
S. C. Smith,
A. Visintin,
E. Kiss-Toth E.,
S. Boussouf,
D. M. Segal,
G. W. Duff, and S. K. Dower.
2000.
Evidence for an accessory protein function for TLR-1 in anti-bacterial responses.
J. Immunol.
165:7125-7132 |
| 36. | Zähringer, U., B. Lindner, and E. T. Rietschel. 1999. Chemical structure of lipid A: recent advances in structural analysis of biologically active molecules, p. 93-114. In H. Brade, S. M. Opal, S. N. Vogel, and D. C. Morrison (ed.), Endotoxin in health and disease. Marcel Dekker, Inc, New York, N.Y. |
| 37. | Zhang, H., J. W. Peterson, D. W. Niesel, and G. R. Klimpel. 1997. Bacterial lipoprotein and lipopolysaccharide act synergistically to induce lethal shock and proinflammatory cytokine production. J. Immunol. 159:4868-4878[Abstract]. |
Infection and Immunity, March 2001, p. 1477-1482, Vol. 69, No. 3
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.3.1477-1482.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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[Abstract] [Full Text] -
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[Abstract] [Full Text] -
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[Abstract] [Full Text] -
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[Abstract] [Full Text] -
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177: 322-332
[Abstract] [Full Text] -
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[Abstract] -
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176: 6888-6899
[Abstract] [Full Text] -
Katz, J., Zhang, P., Martin, M., Vogel, S. N., Michalek, S. M.
(2006). Toll-Like Receptor 2 Is Required for Inflammatory Responses to Francisella tularensis LVS.. Infect. Immun.
74: 2809-2816
[Abstract] [Full Text] -
Teng, Y.-T.A.
(2006). Protective and Destructive Immunity in the Periodontium: Part 1--Innate and Humoral Immunity and the Periodontium. JDR
85: 198-208
[Abstract] [Full Text] -
Querec, T., Bennouna, S., Alkan, S., Laouar, Y., Gorden, K., Flavell, R., Akira, S., Ahmed, R., Pulendran, B.
(2006). Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. JEM
203: 413-424
[Abstract] [Full Text] -
Viriyakosol, S., Matthias, M. A., Swancutt, M. A., Kirkland, T. N., Vinetz, J. M.
(2006). Toll-Like Receptor 4 Protects against Lethal Leptospira interrogans Serovar Icterohaemorrhagiae Infection and Contributes to In Vivo Control of Leptospiral Burden. Infect. Immun.
74: 887-895
[Abstract] [Full Text] -
Galdeano, C. M., Perdigon, G.
(2006). The Probiotic Bacterium Lactobacillus casei Induces Activation of the Gut Mucosal Immune System through Innate Immunity. CVI
13: 219-226
[Abstract] [Full Text] -
Lee, S.-H., Kim, K.-K., Rhyu, I.-C., Koh, S., Lee, D.-S., Choi, B.-K.
(2006). Phenol/water extract of Treponema socranskii subsp. socranskii as an antagonist of Toll-like receptor 4 signalling. Microbiology
152: 535-546
[Abstract] [Full Text] -
Gibson, F.C. III, Yumoto, H., Takahashi, Y., Chou, H.-H., Genco, C.A.
(2006). Innate Immune Signaling and Porphyromonas gingivalis-accelerated Atherosclerosis. JDR
85: 106-121
[Abstract] [Full Text] -
Hashimoto, M., Tawaratsumida, K., Kariya, H., Aoyama, K., Tamura, T., Suda, Y.
(2006). Lipoprotein is a predominant Toll-like receptor 2 ligand in Staphylococcus aureus cell wall components. Int Immunol
18: 355-362
[Abstract] [Full Text] -
Nahori, M.-A., Fournie-Amazouz, E., Que-Gewirth, N. S., Balloy, V., Chignard, M., Raetz, C. R. H., Saint Girons, I., Werts, C.
(2005). Differential TLR Recognition of Leptospiral Lipid A and Lipopolysaccharide in Murine and Human Cells. J. Immunol.
175: 6022-6031
[Abstract] [Full Text] -
Netea, M. G., Van der Meer, J. W. M., Sutmuller, R. P., Adema, G. J., Kullberg, B.-J.
(2005). From the Th1/Th2 Paradigm towards a Toll-Like Receptor/T-Helper Bias. Antimicrob. Agents Chemother.
49: 3991-3996
[Full Text] -
Mancuso, G., Midiri, A., Biondo, C., Beninati, C., Gambuzza, M., Macri, D., Bellantoni, A., Weintraub, A., Espevik, T., Teti, G.
(2005). Bacteroides fragilis-Derived Lipopolysaccharide Produces Cell Activation and Lethal Toxicity via Toll-Like Receptor 4. Infect. Immun.
73: 5620-5627
[Abstract] [Full Text] -
Cole, B. C., Mu, H.-H., Pennock, N. D., Hasebe, A., Chan, F. V., Washburn, L. R., Peltier, M. R.
(2005). Isolation and Partial Purification of Macrophage- and Dendritic Cell-Activating Components from Mycoplasma arthritidis: Association with Organism Virulence and Involvement with Toll-Like Receptor 2. Infect. Immun.
73: 6039-6047
[Abstract] [Full Text] -
Parker, L. C., Whyte, M. K. B., Dower, S. K., Sabroe, I.
(2005). The expression and roles of Toll-like receptors in the biology of the human neutrophil. J. Leukoc. Biol.
77: 886-892
[Abstract] [Full Text] -
Fazeli, A., Bruce, C., Anumba, D.O.
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20: 1372-1378
[Abstract] [Full Text] -
Asai, Y., Hashimoto, M., Fletcher, H. M., Miyake, K., Akira, S., Ogawa, T.
(2005). Lipopolysaccharide Preparation Extracted from Porphyromonas gingivalis Lipoprotein-Deficient Mutant Shows a Marked Decrease in Toll-Like Receptor 2-Mediated Signaling. Infect. Immun.
73: 2157-2163
[Abstract] [Full Text] -
Braedel-Ruoff, S., Faigle, M., Hilf, N., Neumeister, B., Schild, H.
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11: 89-96
[Abstract] -
Lentschat, A., Karahashi, H., Michelsen, K. S., Thomas, L. S., Zhang, W., Vogel, S. N., Arditi, M.
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174: 4252-4261
[Abstract] [Full Text] -
Jimenez, R., Belcher, E., Sriskandan, S., Lucas, R., McMaster, S., Vojnovic, I., Warner, T. D., Mitchell, J. A.
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102: 4637-4642
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Pulendran, B.
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174: 2457-2465
[Abstract] [Full Text] -
Muthukuru, M., Jotwani, R., Cutler, C. W.
(2005). Oral Mucosal Endotoxin Tolerance Induction in Chronic Periodontitis. Infect. Immun.
73: 687-694
[Abstract] [Full Text] -
Takii, R., Kadowaki, T., Baba, A., Tsukuba, T., Yamamoto, K.
(2005). A Functional Virulence Complex Composed of Gingipains, Adhesins, and Lipopolysaccharide Shows High Affinity to Host Cells and Matrix Proteins and Escapes Recognition by Host Immune Systems. Infect. Immun.
73: 883-893
[Abstract] [Full Text] -
Zhou, Q., Desta, T., Fenton, M., Graves, D. T., Amar, S.
(2005). Cytokine Profiling of Macrophages Exposed to Porphyromonas gingivalis, Its Lipopolysaccharide, or Its FimA Protein. Infect. Immun.
73: 935-943
[Abstract] [Full Text] -
Crane-Godreau, M. A., Wira, C. R.
(2005). CCL20/Macrophage Inflammatory Protein 3{alpha} and Tumor Necrosis Factor Alpha Production by Primary Uterine Epithelial Cells in Response to Treatment with Lipopolysaccharide or Pam3Cys. Infect. Immun.
73: 476-484
[Abstract] [Full Text] -
Takeda, K., Akira, S.
(2005). Toll-like receptors in innate immunity. Int Immunol
17: 1-14
[Abstract] [Full Text] -
Zamboni, D. S., Campos, M. A., Torrecilhas, A. C. T., Kiss, K., Samuel, J. E., Golenbock, D. T., Lauw, F. N., Roy, C. R., Almeida, I. C., Gazzinelli, R. T.
(2004). Stimulation of Toll-like Receptor 2 by Coxiella burnetii Is Required for Macrophage Production of Pro-inflammatory Cytokines and Resistance to Infection. J. Biol. Chem.
279: 54405-54415
[Abstract] [Full Text] -
Re, F., Strominger, J. L.
(2004). IL-10 Released by Concomitant TLR2 Stimulation Blocks the Induction of a Subset of Th1 Cytokines That Are Specifically Induced by TLR4 or TLR3 in Human Dendritic Cells. J. Immunol.
173: 7548-7555
[Abstract] [Full Text] -
Hart, A L, Lammers, K, Brigidi, P, Vitali, B, Rizzello, F, Gionchetti, P, Campieri, M, Kamm, M A, Knight, S C, Stagg, A J
(2004). Modulation of human dendritic cell phenotype and function by probiotic bacteria. Gut
53: 1602-1609
[Abstract] [Full Text] -
Hashimoto, M., Asai, Y., Ogawa, T.
(2004). Separation and structural analysis of lipoprotein in a lipopolysaccharide preparation from Porphyromonas gingivalis. Int Immunol
16: 1431-1437
[Abstract] [Full Text] -
Duenas, A. I., Orduna, A., Crespo, M. S., Garcia-Rodriguez, C.
(2004). Interaction of endotoxins with Toll-like receptor 4 correlates with their endotoxic potential and may explain the proinflammatory effect of Brucella spp. LPS. Int Immunol
16: 1467-1475
[Abstract] [Full Text] -
Triantafilou, M., Manukyan, M., Mackie, A., Morath, S., Hartung, T., Heine, H., Triantafilou, K.
(2004). Lipoteichoic Acid and Toll-like Receptor 2 Internalization and Targeting to the Golgi Are Lipid Raft-dependent. J. Biol. Chem.
279: 40882-40889
[Abstract] [Full Text] -
Darveau, R. P., Pham, T.-T. T., Lemley, K., Reife, R. A., Bainbridge, B. W., Coats, S. R., Howald, W. N., Way, S. S., Hajjar, A. M.
(2004). Porphyromonas gingivalis Lipopolysaccharide Contains Multiple Lipid A Species That Functionally Interact with Both Toll-Like Receptors 2 and 4. Infect. Immun.
72: 5041-5051
[Abstract] [Full Text] -
Erridge, C., Pridmore, A., Eley, A., Stewart, J., Poxton, I. R.
(2004). Lipopolysaccharides of Bacteroides fragilis, Chlamydia trachomatis and Pseudomonas aeruginosa signal via Toll-like receptor 2. J Med Microbiol
53: 735-740
[Abstract] [Full Text] -
Liu, N., Montgomery, R. R., Barthold, S. W., Bockenstedt, L. K.
(2004). Myeloid Differentiation Antigen 88 Deficiency Impairs Pathogen Clearance but Does Not Alter Inflammation in Borrelia burgdorferi-Infected Mice. Infect. Immun.
72: 3195-3203
[Abstract] [Full Text] -
Zahringer, U., Lindner, B., Knirel, Y. A., van den Akker, W. M. R., Hiestand, R., Heine, H., Dehio, C.
(2004). Structure and Biological Activity of the Short-chain Lipopolysaccharide from Bartonella henselae ATCC 49882T. J. Biol. Chem.
279: 21046-21054
[Abstract] [Full Text] -
Karlsson, H., Larsson, P., Wold, A. E., Rudin, A.
(2004). Pattern of Cytokine Responses to Gram-Positive and Gram-Negative Commensal Bacteria Is Profoundly Changed when Monocytes Differentiate into Dendritic Cells. Infect. Immun.
72: 2671-2678
[Abstract] [Full Text] -
Narimatsu, M., Noiri, Y., Itoh, S., Noguchi, N., Kawahara, T., Ebisu, S.
(2004). Essential Role for the gtfA Gene Encoding a Putative Glycosyltransferase in the Adherence of Porphyromonas gingivalis. Infect. Immun.
72: 2698-2702
[Abstract] [Full Text] -
Mazzoni, A., Segal, D. M.
(2004). Controlling the Toll road to dendritic cell polarization. J. Leukoc. Biol.
75: 721-730
[Abstract] [Full Text] -
Dillon, S., Agrawal, A., Van Dyke, T., Landreth, G., McCauley, L., Koh, A., Maliszewski, C., Akira, S., Pulendran, B.
(2004). A Toll-Like Receptor 2 Ligand Stimulates Th2 Responses In Vivo, via Induction of Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase and c-Fos in Dendritic Cells. J. Immunol.
172: 4733-4743
[Abstract] [Full Text] -
Parker, L. C., Whyte, M. K. B., Vogel, S. N., Dower, S. K., Sabroe, I.
(2004). Toll-Like Receptor (TLR)2 and TLR4 Agonists Regulate CCR Expression in Human Monocytic Cells. J. Immunol.
172: 4977-4986
[Abstract] [Full Text] -
Hongkuan Fan, , Cook, J. A.
(2004). Review: Molecular mechanisms of endotoxin tolerance. Innate Immunity
10: 71-84
[Abstract] -
Sprong, T., Netea, M. G., van der Ley, P., Verver-Jansen, T. J. G., Jacobs, L. E. H., Stalenhoef, A., van der Meer, J. W. M., van Deuren, M.
(2004). Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria. J. Lipid Res.
45: 742-749
[Abstract] [Full Text] -
Honstettre, A., Ghigo, E., Moynault, A., Capo, C., Toman, R., Akira, S., Takeuchi, O., Lepidi, H., Raoult, D., Mege, J.-L.
(2004). Lipopolysaccharide from Coxiella burnetii Is Involved in Bacterial Phagocytosis, Filamentous Actin Reorganization, and Inflammatory Responses through Toll-Like Receptor 4. J. Immunol.
172: 3695-3703
[Abstract] [Full Text] -
Murphy, T. J., Paterson, H. M., Mannick, J. A., Lederer, J. A.
(2004). Injury, sepsis, and the regulation of Toll-like receptor responses. J. Leukoc. Biol.
75: 400-407
[Abstract] [Full Text] -
Lotz, S., Aga, E., Wilde, I., van Zandbergen, G., Hartung, T., Solbach, W., Laskay, T.
(2004). Highly purified lipoteichoic acid activates neutrophil granulocytes and delays their spontaneous apoptosis via CD14 and TLR2. J. Leukoc. Biol.
75: 467-477
[Abstract] [Full Text] -
Campos, M. A., Rosinha, G. M. S., Almeida, I. C., Salgueiro, X. S., Jarvis, B. W., Splitter, G. A., Qureshi, N., Bruna-Romero, O., Gazzinelli, R. T., Oliveira, S. C.
(2004). Role of Toll-Like Receptor 4 in Induction of Cell-Mediated Immunity and Resistance to Brucella abortus Infection in Mice. Infect. Immun.
72: 176-186
[Abstract] [Full Text] -
Coats, S. R., Reife, R. A., Bainbridge, B. W., Pham, T.-T. T., Darveau, R. P.
(2003). Porphyromonas gingivalis Lipopolysaccharide Antagonizes Escherichia coli Lipopolysaccharide at Toll-Like Receptor 4 in Human Endothelial Cells. Infect. Immun.
71: 6799-6807
[Abstract] [Full Text] -
Murray, D. A, Wilton, J. M. A.
(2003). Lipopolysaccharide from the Periodontal Pathogen Porphyromonas gingivalis Prevents Apoptosis of HL60-Derived Neutrophils In Vitro. Infect. Immun.
71: 7232-7235
[Abstract] [Full Text] -
Agrawal, S., Agrawal, A., Doughty, B., Gerwitz, A., Blenis, J., Van Dyke, T., Pulendran, B.
(2003). Cutting Edge: Different Toll-Like Receptor Agonists Instruct Dendritic Cells to Induce Distinct Th Responses via Differential Modulation of Extracellular Signal-Regulated Kinase-Mitogen-Activated Protein Kinase and c-Fos. J. Immunol.
171: 4984-4989
[Abstract] [Full Text] -
Meng, G., Grabiec, A., Vallon, M., Ebe, B., Hampel, S., Bessler, W., Wagner, H., Kirschning, C. J.
(2003). Cellular Recognition of Tri-/Di-palmitoylated Peptides Is Independent from a Domain Encompassing the N-terminal Seven Leucine-rich Repeat (LRR)/LRR-like Motifs of TLR2. J. Biol. Chem.
278: 39822-39829
[Abstract] [Full Text] -
Han, S. H., Kim, J. H., Martin, M., Michalek, S. M., Nahm, M. H.
(2003). Pneumococcal Lipoteichoic Acid (LTA) Is Not as Potent as Staphylococcal LTA in Stimulating Toll-Like Receptor 2. Infect. Immun.
71: 5541-5548
[Abstract] [Full Text] -
Li, Q., Cherayil, B. J.
(2003). Role of Toll-Like Receptor 4 in Macrophage Activation and Tolerance during Salmonella enterica Serovar Typhimurium Infection. Infect. Immun.
71: 4873-4882
[Abstract] [Full Text] -
Smith, M. F. Jr., Mitchell, A., Li, G., Ding, S., Fitzmaurice, A. M., Ryan, K., Crowe, S., Goldberg, J. B.
(2003). Toll-like Receptor (TLR) 2 and TLR5, but Not TLR4, Are Required for Helicobacter pylori-induced NF-{kappa}B Activation and Chemokine Expression by Epithelial Cells. J. Biol. Chem.
278: 32552-32560
[Abstract] [Full Text] -
Sabroe, I., Read, R. C., Whyte, M. K. B., Dockrell, D. H., Vogel, S. N., Dower, S. K.
(2003). Toll-Like Receptors in Health and Disease: Complex Questions Remain. J. Immunol.
171: 1630-1635
[Full Text] -
Yamazaki, K., Ueki-Maruyama, K., Oda, T., Tabeta, K., Shimada, Y., Tai, H., Nakajima, T., Yoshie, H., Herawati, D., Seymour, G.J.
(2003). Single-nucleotide Polymorphism in the CD14 Promoter and Periodontal Disease Expression in a Japanese Population. JDR
82: 612-616
[Abstract] [Full Text] -
Heldwein, K. A., Liang, M. D., Andresen, T. K., Thomas, K. E., Marty, A. M., Cuesta, N., Vogel, S. N., Fenton, M. J.
(2003). TLR2 and TLR4 serve distinct roles in the host immune response against Mycobacterium bovis BCG. J. Leukoc. Biol.
74: 277-286
[Abstract] [Full Text] -
Pinhal-Enfield, G., Ramanathan, M., Hasko, G., Vogel, S. N., Salzman, A. L., Boons, G.-J., Leibovich, S. J.
(2003). An Angiogenic Switch in Macrophages Involving Synergy between Toll-Like Receptors 2, 4, 7, and 9 and Adenosine A2A Receptors. Am. J. Pathol.
163: 711-721
[Abstract] [Full Text]
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