Critical role for macrophage migration inhibitory factor (MIF) in Ross River virus-induced arthritis and myositis
Autor(es): Herrero Lara J, Nelson Michelle, Srikiatkhachorn Anon, Gu Ran, Anantapreecha Surapee, Fingerle-Rowson Günter, Bucala Richard, Morand Eric, Santos Leilani L, Mahalingam Suresh
Resumo: Arthrogenic alphaviruses, such as Ross River virus (RRV), chikungunya, Sindbis, mayaro - o'nyong-nyong viruses circulate endemically worldwide, frequently causing outbreaks of polyarthritis. The exact mechanisms of how alphaviruses induce polyarthritis remain ill defined, although macrophages are known to play a key role. Macrophage migration inhibitory factor (MIF) is an important cytokine involved in rheumatoid arthritis pathogenesis. Here, we characterize the role of MIF in alphavirus-induced arthritides using a mouse model of RRV-induced arthritis, which has many characteristics of RRV disease in humans. RRV-infected WT mice developed severe disease associated with up-regulated MIF expression in serum - tissues, which corresponded to severe inflammation - tissue damage. MIF-deficient (MIF(-/-)) mice developed mild disease accompanied by a reduction in inflammatory infiltrates - muscle destruction in the tissues, despite having viral titers similar to WT mice. In addition, reconstitution of MIF into MIF(-/-) mice exacerbated RRV disease - treatment of mice with MIF antagonist ameliorated disease in WT mice. Collectively, these findings suggest that MIF plays a critical role in determining the clinical severity of alphavirus-induced musculoskeletal disease - may provide a target for the development of antiviral pharmaceuticals. The prospect being that early treatment with MIF-blocking pharmaceuticals may curtail the debilitating arthritis associated with alphaviral infections.
Imprenta: Proceedings of the National Academy of Sciences of the United States of America, v. 108, n. 29, p. 12048-12053, 2011
Identificador do objeto digital: 10.1073/pnas.1101089108
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Proteins ; Chikungunya virus - Cytokines ; Chikungunya virus - Inflammation ; Chikungunya virus - Viral infections ; Chikungunya virus - RT-PCR ; Chikungunya Virus - Virus ; Chikungunya virus - Public health
Data de publicação: 2011
