NLRP1B and NLRP3 Control the Host Response following Colonization with the Commensal Protist Tritrichomonas musculis.

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. Tritrichomonas musculis, a protozoan gut commensal, strengthens the intestinal host defense against enteric Salmonella infections through Asc- and Il1r1-dependent Th1 and Th17 cell activation. However, the underlying inflammasomes mediating this effect remain unknown. In this study, we report that colonization with T. musculis results in an increase in luminal extracellular ATP that is followed by increased caspase activity, higher cell death, elevated levels of IL-1beta, and increased numbers of IL-18 receptor-expressing Th1 and Th17 cells in the colon. Mice deficient in either Nlrp1b or Nlrp3 failed to display these protozoan-driven immune changes and lost resistance to enteric Salmonella infections even in the presence of T. musculis These findings demonstrate that T. musculis-mediated host protection requires sensors of extracellular and intracellular ATP to confer resistance to enteric Salmonella infections.

与它们的致病性同类不同，共生肠道原生动物是哺乳动物微生物组中被忽视的成员。这些微生物通常通过增强抗微生物的宿主防御，对宿主的肠道免疫稳态产生重大影响。鼠三毛滴虫（Tritrichomonas musculis）是一种原生动物肠道共生体，它通过依赖Asc和Il1r1的Th1和Th17细胞活化来增强肠道宿主对肠道沙门氏菌感染的防御。然而，介导这种效应的潜在炎症小体仍然未知。在这项研究中，我们报道鼠三毛滴虫的定殖导致腔内细胞外ATP增加，随后半胱天冬酶活性增加、细胞死亡增多、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。Nlrp1b或Nlrp3缺陷的小鼠未能表现出这些由原生动物驱动的免疫变化，并且即使存在鼠三毛滴虫，也对肠道沙门氏菌感染失去了抵抗力。这些发现表明，鼠三毛滴虫介导的宿主保护需要细胞外和细胞内ATP的传感器来赋予对肠道沙门氏菌感染的抵抗力。