Journal Article

Interleukin-17 contributes to Ross River virus-induced arthritis and myositis

Cameron, Barbara, Tharmarajah, Kothila, Vider, Jelena, West, Nicholas P., Lloyd, Andrew R., Zaid, Ali, Mostafavi, Helen, Mahalingam, Suresh, Hueston, Linda P., Freitas, Joseph R., Foster, Paul S.

2022

Overview

Arthritogenic alphaviruses are mosquito-borne viruses that are a major cause of infectious arthropathies worldwide, and recent outbreaks of chikungunya virus and Ross River virus (RRV) infections highlight the need for robust intervention strategies. Alphaviral arthritis can persist for months after the initial acute disease, and is mediated by cellular immune responses. A common strategy to limit inflammation and pathology is to dampen the overwhelming inflammatory responses by modulating proinflammatory cytokine pathways. Here, we investigate the contribution of interleukin-17 (IL-17), a cytokine involved in arthropathies such as rheumatoid arthritis, in the development RRV-induced arthritis and myositis. IL-17 was quantified in serum from RRV-infected patients, and mice were infected with RRV and joints and muscle tissues collected to analyse cellular infiltrates, tissue mRNA, cytokine expression, and joint and muscle histopathology. IL-17 expression was increased in musculoskeletal tissues and serum of RRV-infected mice and humans, respectively. IL-17–producing T cells and neutrophils contributed to the cellular infiltrate in the joint and muscle tissue during acute RRV disease in mice. Blockade of IL-17A/F using a monoclonal antibody (mAb) reduced disease severity in RRV-infected mice and led to decreased proinflammatory proteins, cellular infiltration in synovial tissues and cartilage damage, without affecting viral titers in inflamed tissues. IL-17A/F blockade triggered a shift in transcriptional profile of both leukocyte infiltrates and musculoskeletal stromal cells by downregulating proinflammatory genes. This study highlights a previously uncharacterized role for an effector cytokine in alphaviral pathology and points towards potential therapeutic benefit in targeting IL-17 to treat patients presenting with RRV-induced arthropathy.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Alphavirus Infections - immunology / Alphavirus Infections - virology / Animals / Arthritis / Arthritis, Rheumatoid - immunology / Arthritis, Rheumatoid - virology / Biology and Life Sciences / Cartilage / Chlorocebus aethiops / Chronic illnesses / Cytokines / Cytokines - metabolism / Diagnosis / Disease Models, Animal / Experiments / Female / Gene expression / Health aspects / Health care / Histopathology / Humans / Immune response (cell-mediated) / Immunity, Cellular / Infections / Inflammation / Inflammation - immunology / Inflammatory diseases / Interleukin / Interleukin 17 / Interleukin-17 - immunology / Joint diseases / Joints (anatomy) / Leukocytes / Leukocytes (neutrophilic) / Lymphocytes / Lymphocytes T / Male / Medicine and Health Sciences / Mice / Mice, Inbred C57BL / Monoclonal antibodies / Muscles / Musculoskeletal diseases / Myositis / Myositis - immunology / Myositis - virology / Neutrophils / Pathogens / Pathology / Patients / Proteins / Research and Analysis Methods / Rheumatoid arthritis / Risk factors / Rivers / RNA viruses / Ross River virus / Ross River virus - immunology / Stromal cells / Tissue analysis / Tissues / Transcription / Vector-borne diseases / Vero Cells / Viral infections / Viral Load / Viruses