Mannose Binding Lectin Is Required for Alphavirus-Induced Arthritis/Myositis

• DOI: 10.1371/journal.ppat.1002586
• Publication Date: 2012-03-23T13:04:40Z
• Authors: Bronwyn M. Gunn; Thomas E. Morrison; Alan C. Whitmore; Lance K. Blevins; Linda Hueston; Robert J. Fraser; Lara J. Herrero; Ruben Ramirez; Paul N. Smith; Suresh Mahalingam; Mark T. Heise
• Keywords: Ross River virus; Lectin pathway; Complement C1q

Mosquito-borne alphaviruses such as chikungunya virus and Ross River (RRV) are emerging pathogens capable of causing large-scale epidemics virus-induced arthritis myositis. The pathology RRV-induced disease in both humans mice is associated with induction the host inflammatory response within muscle joints, prior studies have demonstrated that complement system contributes to development disease. In this study, we used a mouse model identify characterize which activation pathways mediate progression after infection, identified mannose binding lectin (MBL) pathway, but not classical or alternative pathways, essential for MBL deposition was enhanced RRV infected tissue from wild type deficient exhibited reduced disease, damage, compared wild-type mice. contrast, key components still developed severe Further characterization similar C3−/− mice, viral replication cell recruitment were equivalent animals, suggesting RRV-mediated dependent immune largely dependent. Consistent these findings, human patients diagnosed had elevated serum levels healthy controls, synovial fluid correlated severity These findings demonstrate role promoting suggest pathway may be an effective target therapeutic intervention suffering