Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus
Autor(es): Stoermer Kristina A, Burrack Adam, Oko Lauren, Montgomery Stephanie A, Borst Luke B, Gill Ronald G, Morrison Thomas E
Resumo: Chikungunya virus (CHIKV) - Ross River virus (RRV) cause a debilitating, - often chronic, musculoskeletal inflammatory disease in humans. Macrophages constitute the major inflammatory infiltrates in musculoskeletal tissues during these infections. However, the precise macrophage effector functions that affect the pathogenesis of arthritogenic alphaviruses have not been defined. We hypothesized that the severe damage to musculoskeletal tissues observed in RRV- or CHIKV-infected mice would promote a wound-healing response characterized by M2-like macrophages. Indeed, we found that RRV- - CHIKV-induced musculoskeletal inflammatory lesions, - macrophages present in these lesions, have a unique gene-expression pattern characterized by high expression of arginase 1 - Ym1/Chi3l3 in the absence of FIZZ1/Relm? that is consistent with an M2-like activation phenotype. Strikingly, mice specifically deleted for arginase 1 in neutrophils - macrophages had dramatically reduced viral loads - improved pathology in musculoskeletal tissues at late times post-RRV infection. These findings indicate that arthritogenic alphavirus infection drives a unique myeloid cell activation program in inflamed musculoskeletal tissues that inhibits virus clearance - impedes disease resolution in an arginase 1-dependent manner.
Imprenta: Journal of Immunology, v. 189, n. 8, p. 4047-4059, 2012
Identificador do objeto digital: 10.4049/jimmunol.1201240
Descritores: Chikungunya virus - Cell ; Chikungunya virus - Cytopathology ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology
Data de publicação: 2012
