The weak interaction of LcrV and TLR2 does not contribute to the virulence of Yersinia pestis.
Yersinia pestis and the enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica share the virulence-antigen LcrV. Previously, using reverse genetics we have proven that LcrV contributes to the virulence of Y. enterocolitica serotype O:8 by inducing IL-10 via Toll-like receptor 2 (TLR2). However, both the ability of Y. pestis LcrV to activate TLR2 and a possible role of TLR2-dependent IL-10 induction by LcrV in Y. pestis are not yet known. To eliminate interference from additional protein sequences, we produced LcrVs without affinity tags from Y. pestis and from Y. enterocolitica O:8 (LcrVO:8). LcrVO:8 was much more potent in TLR2-activity than Y. pestis LcrV. To analyse the role of TLR2 in plague, we infected both wild-type and TLR2-/- mice subcutaneously with Y. pestis GB. While TLR2-/- mice exhibited lower blood levels of IL-10 (day 2 post-infection) and of the pro-inflammatory cytokines TNF-alpha, IFN-gamma and MCP-1 (day 4) than wild-type mice, there was no significant difference in survival. The low TLR2-activity of Y. pestis LcrV and associated cytokine expression might explain why - in contrast to Y. enterocolitica O:8 infection - TLR2-deficient mice are not more resistant than wild-type mice in a bubonic plague model.
Reithmeier-Rost
Dagmar
D
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Lehrstuhl Bakteriologie, Pettenkoferstrasse 9a, 80336 München, Germany.
Hill
Jim
J
Elvin
Stephen J
SJ
Williamson
Diane
D
Dittmann
Svea
S
Schmid
Annika
A
Wilharm
Gottfried
G
Sing
Andreas
A
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010930:Plague / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000503:physiopathology; D052899:Pore Forming Cytotoxic Proteins / Q000235:genetics / Q000378:metabolism*; D013047:Specific Pathogen-Free Organisms; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D015010:Yersinia pestis / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*
D000942:Antigens, Bacterial; D016207:Cytokines; C043908:LcrV protein, Yersinia; D052899:Pore Forming Cytotoxic Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2