Temporal Role for MyD88 in a Model of Brucella-Induced Arthritis and Musculoskeletal Inflammation

• Published in: Infection and immunity 2017-03, Vol.85 (3)
• Main Authors: Lacey, Carolyn A, Mitchell, William J, Brown, Charles R, Skyberg, Jerod A
• Format: Article
• Language: English
• Subjects: Adaptive Immunity; Animals; Arthritis, Infectious - genetics; Arthritis, Infectious - metabolism; Arthritis, Infectious - microbiology; Arthritis, Infectious - pathology; Brucella - physiology; Brucellosis - genetics; Brucellosis - metabolism; Brucellosis - microbiology; Brucellosis - pathology; Cytokines - metabolism; Host Response and Inflammation; Inflammation Mediators - metabolism; Mice; Mice, Knockout; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Myositis - genetics; Myositis - metabolism; Myositis - microbiology; Myositis - pathology; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00961-16

spp. are facultative intracellular Gram-negative bacteria that cause the zoonotic disease brucellosis, one of the most common global zoonoses. Osteomyelitis, arthritis, and musculoskeletal inflammation are common focal complications of brucellosis in humans; however, wild-type (WT) mice infected systemically with conventional doses of do not develop these complications. Here we report C57BL/6 WT mice infected via the footpad with 10 to 10 CFU of spp. display neutrophil and monocyte infiltration of the joint space and surrounding musculoskeletal tissue. Joint inflammation is detectable as early as 1 day postinfection and peaks 1 to 2 weeks later, after which WT mice are able to slowly resolve inflammation. B and T cells were dispensable for the onset of swelling but required for resolution of joint inflammation and infection. At early time points, MyD88 mice display decreased joint inflammation, swelling, and proinflammatory cytokine levels relative to WT mice. Subsequently, swelling of MyD88 joints surpassed WT joint swelling, and resolution of joint inflammation was prolonged. Joint bacterial loads in MyD88 mice were significantly greater than those in WT mice by day 3 postinfection and at all time points thereafter. In addition, MyD88 joint inflammatory cytokine levels on day 3 and beyond were similar to WT levels. Collectively these data demonstrate MyD88 signaling mediates early inflammatory responses in the joint but also contributes to subsequent clearance of and resolution of inflammation. This work also establishes a mouse model for studying -induced arthritis, musculoskeletal complications, and systemic responses, which will lead to a better understanding of focal complications of brucellosis.