Yersinia V-antigen exploits toll-like receptor 2 and CD14 for interleukin 10-mediated immunosuppression.
A characteristic of the three human-pathogenic Yersinia spp. (the plague agent Yersinia pestis and the enteropathogenic Yersinia pseudotuberculosis and Yersinia enterocolitica) is the expression of the virulence (V)-antigen (LcrV). LcrV is a released protein which is involved in contact-induced secretion of yersinia antihost proteins and in evasion of the host's innate immune response. Here we report that recombinant LcrV signals in a CD14- and toll-like receptor 2 (TLR2)-dependent fashion leading to immunosuppression by interleukin 10 induction. The impact of this immunosuppressive effect for yersinia pathogenesis is underlined by the observation that TLR2-deficient mice are less susceptible to oral Y. enterocolitica infection than isogenic wild-type animals. In summary, these data demonstrate a new ligand specificity of TLR2, as LcrV is the first known secreted and nonlipidated virulence-associated protein of a Gram-negative bacterium using TLR2 for cell activation. We conclude that yersiniae might exploit host innate pattern recognition molecules and defense mechanisms to evade the host immune response.
Sing
Andreas
A
Max von Pettenkofer-Institut für Hygiene und Medizinische Mikrobiologie, Ludwig-Maximilians-Universität München, Pettenkoferstrasse 9a, Germany.
Rost
Dagmar
D
Tvardovskaia
Natalia
N
Roggenkamp
Andreas
A
Wiedemann
Agnès
A
Kirschning
Carsten J
CJ
Aepfelbacher
Martin
M
Heesemann
Jürgen
J
D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000096:biosynthesis / Q000502:physiology*; D018950:Lipopolysaccharide Receptors / Q000502:physiology*; D008070:Lipopolysaccharides / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D015007:Yersinia / Q000276:immunology / Q000502:physiology*; D015009:Yersinia Infections / Q000276:immunology
D000942:Antigens, Bacterial; D029721:Drosophila Proteins; C043908:LcrV protein, Yersinia; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D016753:Interleukin-10