Evaluation Th17 and Treg Cells During Chronic Chikungunya Infection

Abstract

Our aim was to evaluate the role of Th17 and its balance with Treg cells in defining CHIK chronification pathogenesis, as well as its association with clinical scores. We hypothesized that given that Chikungunya (CHIK) is caused by an arthritogenic alphavirus and possess several similarities with rheumatoid arthritis (RA), both characterized by Th17 cells playing a pathogenic role, in association with limited studies on the role of T cells regarding this CHIK chronification process. To reach this aim, without suitable animal models of CHIKV to properly assess the development of disease clinical signs, we developed a model of CHIK in DBA1/J mice associated with collagen-induced arthritis (CIA). Virus titration was obtained through One Step qPCR. Flow cytometry analyses were performed through cells isolation of draining lymph nodes from CHIKV previously infected (n=6), CIA (n=6) and CHIKV+CIA (n=7). As for humans, peripheral blood samples were obtained, controls (n=6), acute patients (n=6) and chronic patients (n=6). It was observed that our model was able to address clinical scores, such as develop joint swelling. Results showed that association with CHIKV infection increased clinical scores, number of paws involved, and the incidence of arthritis. Analyses of transcripts demonstrated an increased IL-17a and FoxP3 mRNA, however anti-inflammatory cytokines, such as IL-10, was diminished in animals infected with CHIKV. In humans, Treg frequencies presented diminished Treg number and percentage in patients in the chronic and acute stage compared with control individuals. Therefore, our results suggest an important role of T cell response in CHIK infection chronification.