Purinergic P2X7 Receptor Mediates the Elimination of Trichinella spiralis by Activating NF-κB/NLRP3/IL-1β Pathway in Macrophages

Guan, Fei; Jiang, Wangfang; Bai, Yang; Hou, Xiao; Jiang, Chunjie; Zhang, Chongyang; Jacques, Muziazia Lupemba; Liu, Wenqi; Lei, Jiahui

Trichinellosis is one of most neglected foodborne zoonoses worldwide. During Trichinella spiralis infection, the intestinal immune response is the first line of defense and plays a vital role in the host’s resistance. Previous studies indicate that purinergic P2X7 receptor (P2X7R) and pyrin domain-containing protein 3 (NLRP3) inflammasome are involved in the intestinal immune response in T. spiralis infection. However, the precise role of P2X7R and its effect on NLRP3 remains largely underdetermined. In this study, we aimed to investigate the role of P2X7R in the activation of NLRP3 in macrophages during the intestinal immune response against T. spiralis. We found that T. spiralis infection upregulated expression of P2X7R and activation of NLRP3 in macrophages in mice. In vivo, P2X7R deficiency resulted in increased intestinal adult and muscle larval burdens, along with decreased expression of NLRP3/interleukin-1β (IL-1β) in macrophages from the infected mice with T. spiralis. In In vitro experiments, P2X7R blockade inhibited activation of NLRP3/IL-1β via NF-κB and thus reduced the capacity of macrophages to kill newborn larvae of T. spiralis. These results indicate that P2X7R mediates the elimination of T. spiralis by activating the NF-κB/NLRP3/IL-1β pathway in macrophages. Our findings contribute to the understanding of the intestinal immune mechanism of T. spiralis infection.