IL-10/STAT3 signalling pathway-mediated T-cell suppressors upregulation in severe HFMD with EV71 infection

Enterovirus 71 (EV71) causes outbreaks of hand, foot and mouth disease (HFMD) in many countries, especially in the Asia-Pacific region. The EV71 engages diverse strategies to escape immune responses during infections. Arg-1, iNOS and COX-2 are particular suppressors secreted by MDSCs to inactivate T cells, which have been considered to play a significant role in the immune escape of viruses or malignant tumours. However, whether EV71 escapes the immune response through T-cell suppressors remains unknown. We established an animal model of HFMD by EV71 infection in BALB/c mice. The expressions of cytokines IL-10 and Arg-1, iNOS and COX-2 were detected by ELISA and qRT-PCR. The phosphorylation of STAT3 was detected by western blot. The number of MDSCs in PBMCs was examined by flow cytometry. The number of MDSCs in HFMD mice was significantly higher than that in the control, which is in agreement with the upregulation of T-cell suppressors (Arg-1, iNOS and COX-2) secreted by MDSCs in the infection group. The percentage of the gMDSC subpopulation was significantly increased in severe HFMD mice. The serum level of IL-10 and p-STAT3 were upregulated significantly in the infected group whilst inhibition of IL-10 and STAT3 led to the reduction in the T-cell suppressors. Our results suggest that T-cell suppressors (Arg-1, iNOS and COX-2) upregulated in HFMD in response to EV71 infection is attributable to STAT3 signalling activation triggered by IL-10 induction. We speculate that it was caused by elevation of MDSCs to facilitate the immune escape of EV71 in severe HFMD.