CXCR2 is a critical mediator of Brucella-induced articular inflammation (INC4P.335)

Abstract

Osteoarticular complications are the most common focal manifestation of brucellosis in humans. Little is known about the pathology of osteoarticular brucellosis due to the lack of relevant models. However, we recently reported that ablation of IFN-γ in mice results in articular inflammation during infection with Brucella melitensis. Here, we show that adaptive immune cells are dispensable for Brucella-induced articular inflammation. Wild-type, µMT-/-, and Rag1-/- mice all developed articular inflammation at a similar rate and severity when infected with B. melitensis and depleted of IFN-γ. In addition, minimal levels of cytokines associated with T cell responses were detected in arthritic joints. However, we found increased numbers of neutrophils and macrophages in joints from mice with Brucella-induced arthritis. In addition, the concentration of CCR2 and CXCR2 ligands, was strikingly enhanced in Brucella-infected joints. Interestingly, CXCR2-/-, but not CCR2-/- mice, displayed markedly lower joint inflammation relative to wild-type mice when infected with B. melitensis and depleted of IFN-γ. Collectively, these results show that chemokines, such as CXCR2 ligands, are important mediators of Brucella-induced articular inflammation while adaptive immune cells are not required. Therefore, the targeting of CXCR2 and/or other chemokine receptors may have potential as a complementary antibiotic therapy for the resolution of Brucella-induced arthritis.