CXCR2 Mediates Brucella-Induced Arthritis in Interferon γ-Deficient Mice.
BACKGROUND
Brucella species are facultative intracellular gram-negative bacteria that cause brucellosis, a common global zoonosis. Infection of the joints is the most common focal complication of brucellosis in humans. The purpose of this study was to identify mediators of focal inflammation during brucellosis.


METHODS
Wild-type (WT) mice are naturally resistant to Brucella infection; therefore, we infected anti-interferon γ (IFN-γ)-treated, or IFN-γ(-/-) mice with Brucella to induce osteoarticular and musculoskeletal inflammation, as we previously described. Mice were infected intraperitoneally with Brucella melitensis, and the clinical course of disease, histopathologic changes, and cytokine levels were compared among groups.


RESULTS
Rag1(-/-) mice (B- and T-cell deficient) and µMT(-/-) mice (B-cell deficient) developed paw inflammation at a similar rate and severity as WT mice following infection with B. melitensis and treatment with anti-IFN-γ. Joints from B. melitensis-infected IFN-γ(-/-) mice had markedly increased levels of CCR2 and CXCR2 ligands. While anti-IFN-γ-treated CCR2(-/-) and WT mice behaved similarly, anti-IFN-γ-treated CXCR2(-/-) or IFN-γ(-/-)/CXCR2(-/-) mice had strikingly reduced focal swelling relative to anti-IFN-γ-treated WT or IFN-γ(-/-) mice, respectively. Additionally, neutrophil recruitment was dependent on CXCR2.


CONCLUSIONS
Adaptive immune cells and CCR2 are dispensable, while CXCR2 is necessary for Brucella-induced focal neutrophil recruitment and inflammation.
['Lacey|Carolyn A|CA|', 'Keleher|Lauren L|LL|', 'Mitchell|William J|WJ|', 'Brown|Charles R|CR|', 'Skyberg|Jerod A|JA|']
D000818:Animals D001168:Arthritis D017347:Brucella melitensis D002006:Brucellosis D018836:Inflammation Mediators D007371:Interferon-gamma D051379:Mice D008807:Mice, Inbred BALB C D023063:Receptors, Interleukin-8B
CXCR2 arthritis Brucella brucellosis musculoskeletal osteomyelitis