Macrophage-Derived Proinflammatory Factors Contribute to the Development of Arthritis and Myositis after Infection with an Arthrogenic Alpohavirus

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Title Macrophage-Derived Proinflammatory Factors Contribute to the Development of Arthritis and Myositis after Infection with an Arthrogenic Alpohavirus
Author Lidbury, Brett A.; Rulli, Nestor E.; Suhrbier, Andreas; Smith, Paul N.; McColl, Shaun R.; Cunningham, Anthony L.; Tarkowski, Andrej; Rooijen, Nico van; Fraser, Robert J.; Mahalingam, Suresh
Journal Name Journal of infectious diseases
Editor Martin Hirsch
Year Published 2010
Place of publication United States
Publisher Oxford University Press
Abstract Alphaviruses, such as chikungunya virus and Ross River virus (RRV), are associated with outbreaks of infectious rheumatic disease in humans worldwide. Using an established mouse model of disease that mimicsRRVdisease in humans, we showed that macrophage-derived factors are critical in the development of striated muscle and joint tissue damage. Histologic analyses of muscle and ankle joint tissues demonstrated a substantial reduction in inflammatory infiltrates in infected mice depleted of macrophages (i.e., “macrophage-depleted mice”). Levels of the proinflammatory factors tumor necrosis factor—α, interferon—γ, and macrophage chemoattractant protein—1 were also dramatically reduced in tissue samples obtained from infected macrophage-depleted mice, compared with samples obtained from infected mice without macrophage depletion. These factors were also detected in the synovial fluid of patients with RRV-induced polyarthritis. Neutralization of these factors reduced the severity of disease in mice, whereas blocking nuclear factor κB by treatment with sulfasalazine ameliorated RRV inflammatory disease and tissue damage. To our knowledge, these findings are the first to demonstrate that macrophage-derived products play important roles in the development of arthritis and myositis triggered by alphavirus infection.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1086/587841
Volume 197
Issue Number 11
Page from 1585
Page to 1593
ISSN 0022-1899
Date Accessioned 2011-03-17
Date Available 2011-04-07T05:32:07Z
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Medical Virology
URI http://hdl.handle.net/10072/38004
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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