This Article Full Text (PDF) Other Versions of this Article: IAI.01714-07v1 76/9/4241    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Ehrchen, J. M. Articles by Spahn, T. W. PubMed PubMed Citation Articles by Ehrchen, J. M. Articles by Spahn, T. W.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.01714-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Absence of cutaneous lymph nodes results in Th2 switch and susceptibility in Leishmania major infection

Institute of Immunology, and Department of Dermatology, and Department of Medicine B, Department of Medicine A Münster University Hospital, 48149 Münster, Germany; Washington University of Medicine/Division of Gastroenterology, St. Louis, Missouri 63110, USA

^* To whom correspondence should be addressed. Email: thomas.spahn{at}mho.de.

	Abstract

Lymph nodes (LNs) are important sentinel organs where antigen presenting cells interact with T cells to induce adaptive immune responses. In cutaneous infection of mice with Leishmania (L.) major resistance depends on the induction of a T helper cell (Th)1 mediated cellular immune response in draining, peripheral LNs. We investigated whether draining, peripheral LNs are absolutely required for resistance against L. major infection.

We investigated the course of experimental leishmaniasis in wild type (wt) mice lacking peripheral (p) LNs which we generated by in utero blockade of membrane bound lymphotoxin and in mice lacking peripheral or all LNs due to genetic deletion of lymphotoxin ligands or receptors.

Wt mice of the resistant C57BL/6 strain without local skin draining LNs were still able to generate specific T cell responses, but it yielded Th2 cells. This Th2 switch resulted in severe systemic infection.

We confirmed these results also in mice lacking peripheral LNs due to genetic depletion of lymphotoxin-. The complete absence of LNs due to a genetic depletion of the lymphotoxin--receptor also resulted in a marked deterioration of disease and Th2 switch.

Thus in the absence of pLNs, a L. major specific Th2 response is induced in the remaining secondary lymphoid organs such as spleen and non-skin draining LNs. This indicates a critical requirement for pLNs to induce a protective Th1 immunity and suggests that the decision whether Th1 or Th2 priming to the same antigen occurs, depends on the site of the primary antigen recognition.