气候变化领域集成服务门户(CCPortal): The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6

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DOI	10.1073/pnas.2007807118
	The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6
	Sateriale A.; Gullicksrud J.A.; Engiles J.B.; McLeod B.I.; Kugler E.M.; Henao-Mejia J.; Zhou T.; Ring A.M.; Brodsky I.E.; Hunter C.A.; Striepen B.
发表日期	2021
ISSN	00278424
卷号	118 期号:2
英文摘要	The apicomplexan parasite Cryptosporidium infects the intestinal epithelium. While infection is widespread around the world, children in resource-poor settings suffer a disproportionate disease burden. Cryptosporidiosis is a leading cause of diarrheal disease, responsible for mortality and stunted growth in children. CD4 T cells are required to resolve this infection, but powerful innate mechanisms control the parasite prior to the onset of adaptive immunity. Here, we use the natural mouse pathogen Cryptosporidium tyzzeri to demonstrate that the inflammasome plays a critical role in initiating this early response. Mice lacking core inflammasome components, including caspase-1 and apoptosis-associated speck-like protein, show increased parasite burden and caspase 1 deletion solely in enterocytes phenocopies whole-body knockout (KO). This response was fully functional in germfree mice and sufficient to control Cryptosporidium infection. Inflammasome activation leads to the release of IL-18, and mice that lack IL-18 are more susceptible to infection. Treatment of infected caspase 1 KO mice with recombinant IL-18 is remarkably efficient in rescuing parasite control. Notably, NOD-like receptor family pyrin domain containing 6 (NLRP6) was the only NLR required for innate parasite control. Taken together, these data support a model of innate recognition of Cryptosporidium infection through an NLRP6-dependent and enterocyte-intrinsic inflammasome that leads to the release of IL-18 required for parasite control. © This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY).
英文关键词	Cryptosporidium; Immunity; Inflammasome; NLRP6; Parasite
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/181071
作者单位	Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Pathology and Laboratory Medicine, Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Division of Protective Immunity, Department of Pathology and Laboratory Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, United States; Department of Immunology, Yale School of Medicine, Yale University, New Haven, CT 06519, United States
推荐引用方式 GB/T 7714	Sateriale A.,Gullicksrud J.A.,Engiles J.B.,et al. The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6[J],2021,118(2).
APA	Sateriale A..,Gullicksrud J.A..,Engiles J.B..,McLeod B.I..,Kugler E.M..,...&Striepen B..(2021).The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6.Proceedings of the National Academy of Sciences of the United States of America,118(2).
MLA	Sateriale A.,et al."The intestinal parasite Cryptosporidium is controlled by an enterocyte intrinsic inflammasome that depends on NLRP6".Proceedings of the National Academy of Sciences of the United States of America 118.2(2021).