Contribution of toll-like receptors 2 and 4 in an oral Yersinia enterocolitica mouse infection model.
A characteristic of the three human-pathogenic Yersinia spp. (the plague agent Y. pestis and the enteropathogenic Y. pseudotuberculosis and Y. enterocolitica) is the expression of the virulence (V)-antigen (LcrV). LcrV is a released multifunctional protein which is involved in contact-induced secretion of Yersinia antihost proteins and in evasion of the host innate immune response. Recently, we reported that recombinant LcrV signals in a CD14- and TLR2-dependent fashion leading to immunosuppression by interleukin-10 (IL-10) induction. The impact of this immunosuppressive effect for Yersinia pathogenesis was underlined by the observation that IL-10- and TLR2-deficient mice were found to be less susceptible to Y. enterocolitica infection than isogenic C57BL/6 wild-type animals. In the present study, we show that Y. enterocolitica leads to higher IL-10 and lower TNF-alpha levels in spleens from infected C57BL/6 wild-type mice than in those from TLR2-deficient mice. By comparing Y. enterocolitica infection in TLR2-, TLR4-, and TLR2/TLR4-deficient mice, we found that TLR2 is more important in yersiniosis than TLR4. Strikingly and in contrast to the results obtained in TLR2-deficient mice of C57BL/6 background, TLR2-deficient mice of C3H genetic background were more susceptible to an oral Y. enterocolitica infection than wild-type C3H mice. To our knowledge, this is the first report on a divergent influence of a TLR-deficiency on infection outcome in mice of different genetic backgrounds.
Sing
Andreas
A
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität München, München, Germany.
Tvardovskaia
Natalia
N
Rost
Dagmar
D
Kirschning
Carsten J
CJ
Wagner
Hermann
H
Heesemann
Jürgen
J
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D015009:Yersinia Infections / Q000276:immunology* / Q000382:microbiology; D015008:Yersinia enterocolitica / Q000276:immunology*
D000942:Antigens, Bacterial; C043908:LcrV protein, Yersinia; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10