气候变化领域集成服务门户(CCPortal): Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers

CCPortal

DOI	10.1073/pnas.2013963118
	Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers
	Ventayol P.S.; Geiser P.; Di Martino M.L.; Florbrant A.; Fattinger S.A.; Walder N.; Sima E.; Shao F.; Gekara N.O.; Sundbom M.; Hardt W.-D.; Webb D.-L.; Hellström P.M.; Eriksson J.; Sellin M.E.
发表日期	2021
ISSN	00278424
卷号	118 期号:16
英文摘要	The gut epithelium serves to maximize the surface for nutrient and fluid uptake, but at the same time must provide a tight barrier to pathogens and remove damaged intestinal epithelial cells (IECs) without jeopardizing barrier integrity. How the epithelium coordinates these tasks remains a question of significant interest. We used imaging and an optical flow analysis pipeline to study the dynamicity of untransformed murine and human intestinal epithelia, cultured atop flexible hydrogel supports. Infection with the pathogen Salmonella Typhimurium (S.Tm) within minutes elicited focal contractions with inward movements of up to ∼1,000 IECs. Genetics approaches and chimeric epithelial monolayers revealed contractions to be triggered by the NAIP/NLRC4 inflammasome, which sensed type-III secretion system and flagellar ligands upon bacterial invasion, converting the local tissue into a contraction epicenter. Execution of the response required swift sublytic Gasdermin D pore formation, ion fluxes, and the propagation of a myosin contraction pulse across the tissue. Importantly, focal contractions preceded, and could be uncoupled from, the death and expulsion of infected IECs. In both two-dimensional monolayers and three-dimensional enteroids, multiple infection-elicited contractions coalesced to produce shrinkage of the epithelium as a whole. Monolayers deficient for Caspase-1(-11) or Gasdermin D failed to elicit focal contractions but were still capable of infected IEC death and expulsion. Strikingly, these monolayers lost their integrity to a markedly higher extent than wild-type counterparts. We propose that prompt NAIP/NLRC4/Caspase-1/Gasdermin D/myosin-dependent contractions allow the epithelium to densify its cell packing in infected regions, thereby preventing tissue disintegration due to the subsequent IEC death and expulsion process. © This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
英文关键词	Bacterial infection; Contraction; Epithelium; Inflammasome; Organoid
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/179828
作者单位	Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, 75123, Sweden; Institute of Microbiology, Department of Biology, ETH Zürich, Zürich, 8093, Switzerland; Department of Surgical Sciences, Uppsala University, Uppsala, 75185, Sweden; National Institute of Biological Sciences, Beijing, 102206, China; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, 10691, Sweden; Department of Medical Sciences, Gastroenterology and Hepatology Unit, Uppsala University, Uppsala, 75185, Sweden
推荐引用方式 GB/T 7714	Ventayol P.S.,Geiser P.,Di Martino M.L.,et al. Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers[J],2021,118(16).
APA	Ventayol P.S..,Geiser P..,Di Martino M.L..,Florbrant A..,Fattinger S.A..,...&Sellin M.E..(2021).Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers.Proceedings of the National Academy of Sciences of the United States of America,118(16).
MLA	Ventayol P.S.,et al."Bacterial detection by NAIP/NLRC4 elicits prompt contractions of intestinal epithelial cell layers".Proceedings of the National Academy of Sciences of the United States of America 118.16(2021).