IAI Accepts, published online ahead of print on 19 October 2009

This Article Full Text (PDF) 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 Whitfield, N. N. Articles by Swanson, M. S. PubMed PubMed Citation Articles by Whitfield, N. N. Articles by Swanson, M. S.

 Previous Article  |  Next Article 

Infect. Immun. doi:10.1128/IAI.00070-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mouse Macrophages are Permissive to Motile Legionella Species that Fail to Trigger Pyroptosis

Natalie N. Whitfield, Brenda G. Byrne, and Michele S. Swanson^*

Cellular and Molecular Biology Program and Department of Microbiology & Immunology, University of Michigan Medical School, Ann Arbor, MI

^* To whom correspondence should be addressed. Email: mswanson{at}umich.edu.

Legionella pneumophila, a motile opportunistic pathogen of humans, is restricted from replicating in the lungs of C57BL/6 mice. Resistance of mouse macrophages to L. pneumophila depends on recognition of cytosolic flagellin. Once detected by the NOD-like receptors Naip5 and Ipaf (Nlrc4), flagellin triggers pyroptosis, a pro-inflammatory cell death. In contrast, motile strains of L. parisiensis and L. tucsonensis replicate profusely within C57BL/6 macrophages, similar to a flagellin-deficient L. pneumophila. To gain insight to how motile species escape innate defense mechanisms of mice, we compared their impact on macrophages. L. parisiensis and L. tucsonensis do not induce pro-inflammatory cell death, as measured by LDH release and IL-1 secretion. However, flagellin isolated from L. parisiensis and L. tucsonensis triggers cell death and IL-1 secretion when transfected into the cytosol of macrophages. Neither strain displays three characteristics of the canonical L. pneumophila Dot/Icm type IV secretion system: sodium sensitivity, LAMP-1 evasion, and pore formation. Therefore, we postulate that when L. parisiensis and L. tucsonensis invade a mouse macrophage, flagellin is confined to the phagosome, protecting the bacteria from recognition by the cytosolic surveillance system and allowing the Legionella to replicate. Despite their superior capacity to multiply in mouse macrophages, L. parisiensis and L. tucsonensis have only been associated with two cases of disease, both in renal transplant patients. These results point to the complexity of disease, a product of the pathogenic potential of the microbe, as defined in the laboratory, and the capacity of the host to mount a measured defense.