EV-A71 induced IL-1β production in THP-1 macrophages is dependent on NLRP3, RIG-I, and TLR3

• Published in: Scientific reports Vol. 12; no. 1; p. 21425
• Main Authors: Huang, Hsing-I, Chio, Chi-Chong, Lin, Jhao-Yin, Chou, Chia-Jung, Lin, Chia-Chen, Chen, Shih-Hsiang, Yu, Liang-Sheng
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 11.12.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Antigens, Viral; Caspase 1; Caspase 8; Cytokines; Disease; Enterovirus; Enterovirus Infections; Humans; IL-1β; Infections; Inflammasomes; Macrophages; Medicine; Nervous system; Neurological complications; Pathogenesis; Pattern recognition; Pattern recognition receptors; Proteins; Severe acute respiratory syndrome coronavirus 2; TLR3 protein; Toll-Like Receptor 3; Toll-like receptors; Viral infections; Viruses
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-25458-x

Enterovirus A71 (EV-A71) is an emerging enterovirus that can cause neurological complications. Enhanced serum IL-1β levels were observed in EV-A71 patients with severe neurological symptoms. However, the roles of sensors in enterovirus-induced IL-1β production are unclear. In this study, we identified that pattern recognition receptors, including RIG-I, TLR3, and TLR8, are implicated in EV-A71-triggered IL-1β release in human macrophages. EV-A71 infection results in caspase-1 and caspase-8, which act as regulators of EV-A71-induced NLRP3 and RIG-I inflammasome activation. Moreover, knockdown of the expression of TLR3 and TLR8 decreased the released IL-1β in an NLRP3-dependent manner. Since TLR3 and TLR8 ligands promote NLRP3 inflammasome activation via caspase-8, the alternative pathway may be involved. In summary, these results indicate that activation of the NLRP3 and RIG-I inflammasomes in EV-A71-infected macrophages is mediated by caspase-1 and caspase-8 and affected by TLRs, including TLR3 and TLR8.