We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Mycoplasma superantigen initiates a TLR4-dependent Th17 cascade that enhances arthritis after blocking B7-1 in M ycoplasma arthritidis-infected mice.
- Authors
Mu, Hong‐Hua; Nourian, Maziar M.; Jiang, Hua Hui; Tran, Justin W.; Cole, Barry C.
- Abstract
M ycoplasma arthritidis is a natural pathogen of rodents causing arthritis, toxic shock and necrotizing fasciitis. It secretes a potent superantigen ( SAg), MAM, that differentially affects the immune system depending upon presence or absence of TLR4, thus potentially influencing disease outcomes. Here, we establish that antibody to co-stimulatory molecule B7-1( CD80) enhances arthritis in wild-type C3 H/ HeSnJ ( TLR2+4+) mice but suppresses arthritis in TLR4-defect C3 H/ HeJ ( TLR2+4−) mice. Also, blockade of the B7-1/ CD28 co-stimulatory pathway in C3 H/ HeSnJ mice resulted in a marked increase in an alternative co-stimulatory pathway ICOS/ ICOSL that was associated with elevation of the IL-17/ Th17cascade with enhanced IL-23, IL-6, and the RORγt and STAT3 transcriptional factors on CD4+ T cells. Anti- B7-1 also increased inflammatory chemokines and the stress protein HMGB1 that promotes cellular infiltration to joints. Using a MAM-deficient strain of M . arthritidis, a monoclonal antibody to TLR4 and a TLR4-defective mouse strain, we established that both MAM and TLR4 are required for the systemic and local joint triggering of the Th17/ IL-17 cascade in mice treated with anti- B7-1 antibody. Importantly, blocking of IL-17 with anti- IL-17 antibody suppressed the elevated arthritis in M . arthritidis-infected mice treated with anti- B7-1 antibody. Thus, this unique model of arthritis illustrates how microbial agonists can bridgeinnate and adaptive immune responses to redirect signalling pathways, thus promoting chronic inflammatory and autoimmune disease.
- Subjects
MYCOPLASMA; SUPERANTIGENS; TOLL-like receptors; ARTHRITIS; LABORATORY mice; PATHOGENIC microorganisms; TOXIC shock syndrome; NECROTIZING fasciitis
- Publication
Cellular Microbiology, 2014, Vol 16, Issue 6, p896
- ISSN
1462-5814
- Publication type
Article
- DOI
10.1111/cmi.12247