Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Clinical Laboratory, Changzhi People's Hospital, Changzhi, China.
Infect Immun. 2021 Apr 16;89(5). doi: 10.1128/IAI.00683-20.
Trichinellosis is one of most neglected foodborne zoonoses worldwide. During 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 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 We found that infection upregulated expression of P2X7R and activation of NLRP3 in macrophages in mice. , 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 In experiments, P2X7R blockade inhibited activation of NLRP3/IL-1β via NF-κB and thus reduced the capacity of macrophages to kill newborn larvae of These results indicate that P2X7R mediates the elimination of by activating the NF-κB/NLRP3/IL-1β pathway in macrophages. Our findings contribute to the understanding of the intestinal immune mechanism of infection.
旋毛虫病是全球最被忽视的食源性病原体之一。在感染过程中,肠道免疫反应是第一道防线,在宿主抵抗中起着至关重要的作用。先前的研究表明,嘌呤能 P2X7 受体(P2X7R)和含 pyrin 域蛋白 3(NLRP3)炎性小体参与感染中的肠道免疫反应。然而,P2X7R 的精确作用及其对 NLRP3 的影响在很大程度上仍未确定。在本研究中,我们旨在研究 P2X7R 在肠道免疫反应中对抗旋毛虫感染时激活 NLRP3 在巨噬细胞中的作用。我们发现,旋毛虫感染上调了小鼠巨噬细胞中 P2X7R 的表达和 NLRP3 的激活。此外,P2X7R 缺乏导致感染小鼠的肠道成虫和肌肉幼虫负担增加,同时巨噬细胞中 NLRP3/白细胞介素-1β(IL-1β)的表达降低。在体外实验中,P2X7R 阻断通过 NF-κB 抑制 NLRP3/IL-1β 的激活,从而降低巨噬细胞杀死新生旋毛虫幼虫的能力。这些结果表明,P2X7R 通过激活巨噬细胞中的 NF-κB/NLRP3/IL-1β 通路介导旋毛虫的清除。我们的研究结果有助于理解旋毛虫感染的肠道免疫机制。