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

Brett Lidbury, Nestor Rulli, Andreas Suhrbier, Paul Smith, Shaun McColl, Anthony Cunningham, Andrzej Tarkowski, Nico van Rooijen, Robert Fraser, Suresh Mahalingam

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    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.
    Original languageEnglish
    Pages (from-to)1585-1593
    Number of pages9
    JournalJournal of Infectious Diseases
    Volume197
    Issue number11
    DOIs
    Publication statusPublished - 2008

    Fingerprint

    Alphavirus
    Myositis
    Arthritis
    Macrophages
    Ross River virus
    Infection
    Alphavirus Infections
    Chikungunya virus
    Muscles
    Sulfasalazine
    Striated Muscle
    Ankle Joint
    Synovial Fluid
    Chemotactic Factors
    Virus Diseases
    Rheumatic Diseases
    Interferons
    Disease Outbreaks
    Communicable Diseases
    Tumor Necrosis Factor-alpha

    Cite this

    Lidbury, Brett ; Rulli, Nestor ; Suhrbier, Andreas ; Smith, Paul ; McColl, Shaun ; Cunningham, Anthony ; Tarkowski, Andrzej ; van Rooijen, Nico ; Fraser, Robert ; Mahalingam, Suresh. / Macrophage-derived Proinflammatory Factors Contribute to the Development of Arthritis and Myositis after Infection with an Arthrogenic Alphavirus. In: Journal of Infectious Diseases. 2008 ; Vol. 197, No. 11. pp. 1585-1593.
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    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.",
    author = "Brett Lidbury and Nestor Rulli and Andreas Suhrbier and Paul Smith and Shaun McColl and Anthony Cunningham and Andrzej Tarkowski and {van Rooijen}, Nico and Robert Fraser and Suresh Mahalingam",
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    Lidbury, B, Rulli, N, Suhrbier, A, Smith, P, McColl, S, Cunningham, A, Tarkowski, A, van Rooijen, N, Fraser, R & Mahalingam, S 2008, 'Macrophage-derived Proinflammatory Factors Contribute to the Development of Arthritis and Myositis after Infection with an Arthrogenic Alphavirus', Journal of Infectious Diseases, vol. 197, no. 11, pp. 1585-1593. https://doi.org/10.1086/587841

    Macrophage-derived Proinflammatory Factors Contribute to the Development of Arthritis and Myositis after Infection with an Arthrogenic Alphavirus. / Lidbury, Brett; Rulli, Nestor; Suhrbier, Andreas; Smith, Paul; McColl, Shaun; Cunningham, Anthony; Tarkowski, Andrzej; van Rooijen, Nico; Fraser, Robert; Mahalingam, Suresh.

    In: Journal of Infectious Diseases, Vol. 197, No. 11, 2008, p. 1585-1593.

    Research output: Contribution to journalArticle

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    AU - Lidbury, Brett

    AU - Rulli, Nestor

    AU - Suhrbier, Andreas

    AU - Smith, Paul

    AU - McColl, Shaun

    AU - Cunningham, Anthony

    AU - Tarkowski, Andrzej

    AU - van Rooijen, Nico

    AU - Fraser, Robert

    AU - Mahalingam, Suresh

    PY - 2008

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    N2 - 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.

    AB - 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.

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