@article{0aa52d386909401985cd20031a8cc9a4,
title = "Yersinia pseudotuberculosis YopE prevents uptake by M cells and instigates M cell extrusion in human ileal enteroid-derived monolayers",
abstract = "Many pathogens use M cells to access the underlying Peyer{\textquoteright}s patches and spread to systemic sites via the lymph as demonstrated by ligated loop murine intestinal models. However, the study of interactions between M cells and microbial pathogens has stalled due to the lack of cell culture systems. To overcome this obstacle, we use human ileal enteroid-derived monolayers containing five intestinal cell types including M cells to study the interactions between the enteric pathogen, Yersinia pseudotuberculosis (Yptb), and M cells. The Yptb type three secretion system (T3SS) effector Yops inhibit host defenses including phagocytosis and are critical for colonization of the intestine and Peyer{\textquoteright}s patches. Therefore, it is not understood how Yptb traverses through M cells to breach the epithelium. By growing Yptb under two physiological conditions that mimic the early infectious stage (low T3SS-expression) or host-adapted stage (high T3SS-expression), we found that large numbers of Yptb specifically associated with M cells, recapitulating murine studies. Transcytosis through M cells was significantly higher by Yptb expressing low levels of T3SS, because YopE and YopH prevented Yptb uptake. YopE also caused M cells to extrude from the epithelium without inducing cell-death or disrupting monolayer integrity. Sequential infection with early infectious stage Yptb reduced host-adapted Yptb association with M cells. These data underscore the strength of enteroids as a model by discovering that Yops impede M cell function, indicating that early infectious stage Yptb more effectively penetrates M cells while the host may defend against M cell penetration of host-adapted Yptb.",
keywords = "M cell, Yersinia pseudotuberculosis, YopE, YopH, cell extrusion, human ileal enteroid, organoid, polarized epithelial, transcytosis, type three secretion system",
author = "Fasciano, {Alyssa C.} and Dasanayake, {Gaya S.} and Estes, {Mary K.} and Zachos, {Nicholas C.} and Breault, {David T.} and Isberg, {Ralph R.} and Shumin Tan and Joan Mecsas",
note = "Funding Information: This work was supported by the National Institute of Allergy and Infectious Diseases [U19AI131126]; National Institute of Allergy and Infectious Diseases [U19AI116497]; National Institute of Allergy and Infectious Diseases [R21AI128093, U19AI131126]; National Institute of Allergy and Infectious Diseases [T32AI007077]; National institute of diabetes and digestive and kidney diseases [DK034854]; National institute of diabetes and digestive and kidney diseases [DK-809502]. We thank Eric Stas (Boston Children{\textquoteright}s Hospital), Igor Brodsky (University of Pennsylvania), Alenka Lovy, members of the Kaplan, Ng, and Ward Labs (Tufts Medical Center), Lamyaa Shaban, Giang Nguyen, Anne McCabe, Pathricia Leus, Rebecca Silver, Yoelkys Morales, and previous members of the Mecsas Lab for technical support, strains, and/or critical reading of the manuscript. This work was supported by NIAID U19AI131126 to RRI (Tufts University School of Medicine) and Dr. Kaplan (Tufts University) with JM serving as Project 2 Leader; NIAID R21AI128093 to JM; NIH U19AI116497 to MKE; the Integrated Physiology Core of the Hopkins Conte Digestive Disease Basic and Translational Research Core Center (NIH DK-809502) for HIE59; and the Tufts Center for Neuroscience Research, P30 NS047243 for confocal imaging. DTB was supported in part by the Harvard Digestive Disease Center P30 DK034854. ACF was supported in part by NIAID T32AI007077. Funding Information: We thank Eric Stas (Boston Children{\textquoteright}s Hospital), Igor Brodsky (University of Pennsylvania), Alenka Lovy, members of the Kaplan, Ng, and Ward Labs (Tufts Medical Center), Lamyaa Shaban, Giang Nguyen, Anne McCabe, Pathricia Leus, Rebecca Silver, Yoelkys Morales, and previous members of the Mecsas Lab for technical support, strains, and/or critical reading of the manuscript. This work was supported by NIAID U19AI131126 to RRI (Tufts University School of Medicine) and Dr. Kaplan (Tufts University) with JM serving as Project 2 Leader; NIAID R21AI128093 to JM; NIH U19AI116497 to MKE; the Integrated Physiology Core of the Hopkins Conte Digestive Disease Basic and Translational Research Core Center (NIH DK-809502) for HIE59; and the Tufts Center for Neuroscience Research, P30 NS047243 for confocal imaging. DTB was supported in part by the Harvard Digestive Disease Center P30 DK034854. ACF was supported in part by NIAID T32AI007077. Publisher Copyright: {\textcopyright} 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.",
year = "2021",
doi = "10.1080/19490976.2021.1988390",
language = "English (US)",
volume = "13",
journal = "Gut Microbes",
issn = "1949-0976",
publisher = "Landes Bioscience",
number = "1",
}