Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; and.
J Immunol. 2022 Apr 1;208(7):1782-1789. doi: 10.4049/jimmunol.2100802. Epub 2022 Mar 7.
Commensal intestinal protozoa, unlike their pathogenic relatives, are neglected members of the mammalian microbiome. These microbes have a significant impact on the host's intestinal immune homeostasis, typically by elevating anti-microbial host defense. , a protozoan gut commensal, strengthens the intestinal host defense against enteric infections through - and -dependent Th1 and Th17 cell activation. However, the underlying inflammasomes mediating this effect remain unknown. In this study, we report that colonization with results in an increase in luminal extracellular ATP that is followed by increased caspase activity, higher cell death, elevated levels of IL-1β, and increased numbers of IL-18 receptor-expressing Th1 and Th17 cells in the colon. Mice deficient in either or failed to display these protozoan-driven immune changes and lost resistance to enteric infections even in the presence of These findings demonstrate that -mediated host protection requires sensors of extracellular and intracellular ATP to confer resistance to enteric infections.
肠道共生原生动物与它们的病原性同类不同，是被忽视的哺乳动物微生物组的成员。这些微生物对宿主的肠道免疫稳态有重大影响，通常通过提高抗微生物宿主防御来实现。一种原生动物肠道共生体，通过依赖 ASC 和 caspase-1 的 Th1 和 Th17 细胞激活，增强了宿主对肠道感染的防御。然而，介导这种效应的潜在炎症小体仍不清楚。在这项研究中，我们报告了与共生的定植导致腔内分泌型细胞外 ATP 的增加，随后 caspase 活性增加、细胞死亡增加、IL-1β水平升高以及结肠中表达 IL-18 受体的 Th1 和 Th17 细胞数量增加。缺乏 或 的小鼠未能显示这些原生动物驱动的免疫变化，即使在存在 的情况下，也失去了对肠道 感染的抵抗力。这些发现表明，宿主保护需要细胞外和细胞内 ATP 的传感器来赋予对肠道 感染的抵抗力。
