- Title
- Interleukin-17 contributes to Ross River virus-induced arthritis and myositis
- Creator
- Mostafavi, Helen; Tharmarajah, Kothila; Vider, Jelena; West, Nicholas P.; Freitas, Joseph R.; Cameron, Barbara; Foster, Paul S.; Hueston, Linda P.; Lloyd, Andrew R.; Mahalingam, Suresh; Zaid, Ali
- Relation
- PLoS Pathogens Vol. 18, Issue 2, no. e1010519
- Publisher Link
- http://dx.doi.org/10.1371/journal.ppat.1010185
- Publisher
- Public Library of Science (PLoS)
- Resource Type
- journal article
- Date
- 2022
- Description
- 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.
- Subject
- interleukin-17; Ross River virus; arthritis; myositis; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1472854
- Identifier
- uon:48937
- Identifier
- ISSN:1553-7366
- Rights
- © 2022 Mostafavi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. (http://creativecommons.org/licenses/by/4.0/).
- Language
- eng
- Full Text
- Reviewed
- Hits: 3918
- Visitors: 3981
- Downloads: 77
Collections
Goal 3: Good Health and Well-Being
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 6 MB | Adobe Acrobat PDF | View Details Download |