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.
Mu
Hong-Hua
HH
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
Humphreys
Jennifer
J
Chan
Fok Vun
FV
Cole
Barry C
BC
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