Open AccessNovel interactions of a microbial superantigen with TLR2 and TLR4 differentially regulate IL‐17 and Th17‐associated cytokines
Author(s) -
Mu HongHua,
Hasebe Akira,
Van Schelt Adam,
Cole Barry C.
Publication year - 2011
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2010.01540.x
Subject(s) - tlr2 , superantigen , biology , interleukin 17 , tlr4 , cytokine , immunology , receptor , microbiology and biotechnology , immune system , t cell , biochemistry
Summary Mycoplasma arthritidis , an inflammatory murine pathogen, secretes a potent superantigen, Mycoplasma arthritidis mitogen (MAM) that contributes to toxic shock, arthritis and skin necrosis. Previously we showed that MAM induced type 2 T‐cell cytokines in mice that express functional TLR2 and TLR4, but type 1 cytokines in mice that lack TLR4 function. We show here that IL‐17, pSTAT3 and retinoid‐related orphan nuclear receptorγt are rapidly expressed in wild‐type C3H/HeSnJ (TLR2+/4+) mice but are significantly delayed in mutant C3H/HeJ (TLR2+/4−) mice. This marked kinetic difference was associated with a high level of IL‐6 in TLR2+/4+ mice versus high levels of IL‐1β and TNFα in TLR2+/4− mice. Also antibodies to IL‐6 and IL‐23, suppressed IL‐17 responses to MAM in TLR2+/4+ mice whereas anti‐IL‐1β, but not anti‐TNFα, enhanced IL‐17 in TLR2+/4− mice. Antibody blocking of TLR4 in TLR2+/4+ mice decreased IL‐17 and IL‐6 but not IL‐23. In addition both IL‐17 and IL‐6 but not IL‐23 were elevated in TLR2 KO mice versus wild‐type TLR2+/4+ mice given MAM. We conclude that the MAM interaction with TLR2 versus TLR4 leads to distinct cytokine pathways mediated primarily by IL‐1β or IL‐6/IL‐17 signalling respectively. Our findings suggest that the differential interaction of MAM with different TLRs might play an important role in disease outcomes by M. arthritidis .