TLR2 and TLR4 differentially regulate B7-1 resulting in distinct cytokine responses to the mycoplasma superantigen MAM as well as to disease induced by Mycoplasma arthritidis.
Mycoplasma arthritidis mitogen (MAM) is a superantigen secreted by M. arthritidis, an agent of murine arthritis and toxicity. We previously demonstrated that C3H mouse sub-strains differing in expression of Toll-like receptor 4 (TLR4), differed in immune reactivity to MAM due to differential engagement of TLR2 and TLR4. Here we examine the role of B7 co-stimulatory molecules in immune outcome and disease manifestations resulting from these different MAM/TLR2 and MAM/TLR4 interactions. Injections of MAM into C3H/HeJ mice upregulated expression of B7-1 but not B7-2 on peritoneal adherent cells, whereas B7-1 expression was lower on cells from C3H/HeSnJ mice. Anti-B7-1 antibody but not anti-B7-2, injected in vivo, changed the type 1 cytokines in MAM-injected C3H/HeJ mice to a type 2 cytokines and, conversely, the type 2 response in C3H/HeSnJ mice injected with anti-B7-1 shifted to a type 1 pattern. Whereas anti-B7-2 exerted no effect on disease in either mouse strain, anti-B7-1 significantly delayed the lethal toxicity of M. arthritidis in C3H/HeJ mice but enhanced arthritis in C3H/HeSnJ mice. Thus, TLR-mediated regulation of B7-1 results in diverse cytokine profiles in C3H sub-strains, and that the interaction of MAM with different TLR(s) may differentially affect cytokine responses and ultimately, M. arthritidis disease.
Division of Rheumatology, Department of Internal Medicine, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, UT 84132, USA. Hong.Mu@m.cc.utah.edu
Hong-Hua
HH
Mu
Jennifer
J
Humphreys
Fok Vun
FV
Chan
Barry C
BC
Cole
D000818:Animals; D000942:Antigens, Bacterial; D001170:Arthritis, Infectious / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology*; D018122:B7-1 Antigen / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D017737:Macrophages, Peritoneal / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D009175:Mycoplasma Infections / Q000276:immunology / Q000382:microbiology / Q000503:physiopathology; D045645:Mycoplasma arthritidis / Q000276:immunology* / Q000472:pathogenicity; D011506:Proteins / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D000942:Antigens, Bacterial; D018122:B7-1 Antigen; D016207:Cytokines; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D018089:Superantigens; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4