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dc.contributor.authorRanganathan, Sridevi
dc.contributor.authorGrassel, Christen L.
dc.contributor.authorDelaine-Elias, BreOnna
dc.contributor.authorBarry, Eileen M.
dc.creatorRanganathan, S.
dc.date.accessioned2019-07-15T18:44:50Z
dc.date.available2019-07-15T18:44:50Z
dc.date.issued2019-04-01
dc.identifier.urihttps://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85063712974&origin=inward
dc.identifier.urihttp://hdl.handle.net/10713/10077
dc.description.abstractThe enteric pathogen Shigella is one of the leading causes of moderate-to-severe diarrhea and death in young children in developing countries. Transformed cell lines and animal models have been widely used to study Shigella pathogenesis. In addition to altered physiology, transformed cell lines are composed of a single cell type that does not sufficiently represent the complex multicellular environment of the human colon. Most available animal models do not accurately mimic human disease. The human intestinal enteroid model, derived from LGR5 stem cell-containing intestinal crypts from healthy subjects, represents a technological leap in human gastrointestinal system modeling and provides a more physiologically relevant system that includes multiple cell types and features of the human intestine. We established the utility of this model for studying basic aspects of Shigella pathogenesis and host responses. In this study, we show that Shigella flexneri is capable of infecting and replicating intracellularly in human enteroids derived from different segments of the intestine. Apical invasion by S. flexneri is very limited but increases 10-fold when enteroids are differentiated to include M cells. Invasion via the basolateral surface was at least 2-log10 units more efficient than apical infection. Increased secretion of interleukin-8 and higher expression levels of the mucin glycoprotein Muc2 were observed in the enteroids following S. flexneri infection. The human enteroid model promises to bridge some of the gaps between traditional cell culture, animal models, and human infection. Copyright © 2019 Ranganathan et al.en_US
dc.description.sponsorshipThis work was supported by NIH grant P01AI125181, NIH grant U19AI109776 and NIH grant P30DK089502.en_US
dc.description.urihttps://www.doi.org/10.1128/IAI.00740-18en_US
dc.language.isoen_USen_US
dc.publisherAmerican Society for Microbiologyen_US
dc.relation.ispartofInfection and Immunityen_US
dc.subjectColonoiden_US
dc.subjectHuman intestinal enteroidsen_US
dc.subjectM cellsen_US
dc.subjectS. flexneri pathogenesisen_US
dc.titleEvaluating shigella flexneri pathogenesis in the human enteroid modelen_US
dc.typeArticleen_US
dc.identifier.doi10.1128/IAI.00740-18
dc.identifier.pmid30642900
dc.relation.volume87


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