Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells

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Mosquito-transmitted chikungunya virus (CHIKV), Ross River virus (RRV), and related alphaviruses cause epidemics involving millions of persons, such as on-going CHIKV outbreaks in the Caribbean and Central and South America. Infection with these viruses results in severe pain due to inflammation of musculoskeletal tissues that can persist for months and even years. There are no specific therapeutics or licensed vaccines for these viruses. Suppressive myeloid cells have been shown to inhibit anti-pathogen immune responses, including T cell responses, which can promote chronic disease. We showed previously that a gene associated with suppressive myeloid cells, arginase 1 (Arg1), was induced in musculoskeletal tissues and macrophages of mice infected with RRV or CHIKV, and mice that lacked Arg1 expression in myeloid cells had reduced viral loads at late times post-infection. Here, we demonstrate that Arg1 is induced in PBMCs isolated from CHIKV-infected patients, and Arg1 expression is associated with viral loads. Moreover, we found that Arg1-expressing myeloid cells inhibit the activation and function of antiviral T cells in RRV-infected mice. These studies underscore the role of suppressive myeloid cells in modulating the T cell response to arthritogenic alphaviruses and provide a therapeutic target to enhance viral clearance and potentially limit chronic disease.

Vyšlo v časopise: Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005191
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005191

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