ILC3 Function as a Double-Edged Sword in EV71 Infection

Enterovirus 71 (EV71) is a common pathogen responsible for hand, foot, and mouth disease (HFMD), leading to severe neurological complications and even death. However, the mechanisms underlying severe EV71-induced disease remain unclear, and no effective specific treatments are available. In this study, we successfully infected mice of different ages using a mouse-adapted EV71 strain, resulting in disease and mortality. We compared immune system responses between infected and uninfected mice of different ages to identify key pathogenic targets during EV71 infection. Our findings revealed that the level of Group 3 Innate Lymphoid Cells (ILC3s) in mice negatively correlated with the severity of disease induced by EV71 infection. We conducted anti-ILC3 cytokine injections and cytokine neutralizing antibody experiments on 14-day-old EV71-infected mice. The results showed that the cytokine IL-17 secreted by ILC3 cells had a mild protective effect, while IL-22 promoted inflammatory responses. Our research demonstrates that ILC3 cells play a dual role in EV71 infection. These findings not only clarify key immune factors in the progression of EV71-induced disease but also provide a promising approach for the early diagnosis and treatment of severe EV71 infections.