Interleukin-17 Contributes to Chikungunya Virus-Induced Disease.

Abstract

ABSTRACTAlphaviral arthritides caused by mosquito-borne arboviruses such as chikungunya virus (CHIKV) can persist for months after the initial acute disease. Here, we investigated the contribution of interleukin-17 (IL-17), a cytokine involved in chronic autoimmune arthropathies such as rheumatoid arthritis, to the development of alphaviral arthropathy. Sera from CHIKV-infected patients who displayed both acute and chronic disease showed high levels of IL-17, IL-6, IL-21, IL-22, and IL-23, especially during the chronic phase of disease. We sought to validate these findings using a mouse model of CHIKV infection and disease using wild-type and IL-17A-deficient mice. Mice were infected with CHIKV, and joint and muscle tissues were harvested at designated time points. Tissue infiltrates were examined by immunohistochemistry, and tissue mRNA and protein expression of cytokines was assessed. Joint and muscle pathology was assessed using histology. CHIKV-infected mice lacking IL-17A showed reduced tissue inflammation and neutrophil infiltration, compared to wild-type mice. These investigations showed a role for IL-17 in the acute phase of CHIKV infection and also during the postacute disease resolution phase.