EV-A71 Induced IL-1Beta Production in THP-1 Macrophages is Dependent on NLRP3, RIG-I, and TLR3

Abstract

Enterovirus A71 (EV-A71) is an emerging enterovirus that can cause neurological complications in young children. The severity of EV71 infection is correlated with the production of cytokines, including IL-6 and IL-1b. Macrophages are specialized immune cells that have been deemed the major cell source for IL-1b. The production of IL-1b is a result of inflammasome activation, an innate immune response that involves the assembly of multiple proteins. However, the mechanisms by which EV-A71 activates inflammasomes are not fully understood. Here, we confirmed that THP-1 macrophages permissive EV-A71 replication. EV-A71 infection is sufficient to trigger IL-1b production in macrophages. Knockdown of NLRP3, RIG-I and TLR3 in macrophages suppressed IL-1b secretion. Moreover, caspase-1 and caspase-8 activation are involved in IL-1b production. In summary, this study showed that NLRP3 and the RNA sensors TLR3 and RIG-I are implicated in EV-A71-induced inflammasome activation in macrophages to facilitate IL-1b production via activated caspase-1 and caspase-8.