J. Heesemann and A. Sing,
Max von Pettenkofer-Institut,
München
The physiological microbial flora of humans is efficiently controlled
by the innate immune system. Microbial agents which are endowed with the capability
to subvert, evade or get under control the innate immune response are defined
as pathogens. Yersinia enterocolitca and Y. pestis evolved
short-distance (sd) and long-distance (ld) weapons to attenuate the primary
inflammatory response. The type III protein secretion system acts as sd-weapon
by injection of effector proteins (Yops) into contacted cells. YopE, YopH,
YopT and YopP downregulate production of proinflammatory cytokines and reactive
oxygen. The long known V-antigen (LcrV) is secreted by yersinia and sensed
by toll-like receptor 2 (TLR2) of macrophages leading to IL-10 induction
and suppression of TNF-a. Preliminary studies revealed that TLR-2 does not only function
as LcrV-signalling surface receptor but also translocates LcrV across the
cytoplasma membrane to intracellular compartments where LcrV meets the two
cytoplasmic microdetectors Nod1 and Nod2. Thus, TLR2 functions as signalling
and shuttle molecule for LcrV. Strikingly LcrV-sensing by Nod1/2 also results
in IL-10 production.
In conclusion, Yersinia is capable to modulate the innate immune
response of the host in the sense of avoidance of a strong inflammatory response.
Sing A., Rost D., Tvardovskaia
N., Roggenkamp A., Wiedemann A., Kirschning C. J., Aepfelbacher M., Heesemann
J. 2002.
Yersinia V-Antigen Exploits
Toll-like Receptor 2 and CD14 for Interleukin 10-mediated Immunosuppression.
J. Exp. Med. 196:
1017-1024.
Sing A, Roggenkamp A, Geiger
AM, Heesemann J. 2002.
Yersinia enterocolitica Evasion
of the Host Innate Immune Response by V Antigen-Induced IL-10 Production of
Macrophages Is Abrogated in IL-10-Deficient Mice.
J Immunol. 168(3):1315-21