Severe enterovirus A71 infection is associated with dysfunction of T cell immune response and alleviated by...

Enterovirus A71 (EV-A71) is the major causative pathogen for severe hand-foot-mouth disease (HFMD), a predominantly childhood-associated communicable disease. The mechanisms that children manifest severe disease progression while adults typically exhibit milder or asymptomatic infections remain incompletely characterized, which hinders the development of effective therapy against this disease. Herein, using the newborn mouse model of EV-A71 infection, we uncovered that the underdevelopment of T cells closely associated with the severity of EV-A71 infection, and EV-A71 infection dramatically impaired T-cell immune response. Moreover, the dysfunction of T-cell immunity contributes to the pathogenesis of EV-A71 infection, as the loss of T cells made neonatal mice highly vulnerable to EV-A71 infection. To further assess the relationship between T-cell immunity and HFMD, we enrolled a cohort of 145 pediatric patients with laboratory-confirmed EV-A71 infection and found that the compromised T-cell immune response is associated with the severity of EV-A71-caused HFMD in these children. Furthermore, we found that the treatment of newborn mice with Astragaloside A, a saponin from the medicinal herb Astragalus membranaceus, showed potent in vivo therapeutic efficacy against EV-A71 infection in a T-cell-dependent manner. In conclusion, these findings uncover the interaction between EV-A71 infection and T-cell immunity, provide novel insights onto the physiological impacts of T cells on the pathogenesis of EV-A71 infection and HFMD, and find a promising immunotherapeutic strategy to treat this viral disease.