Peyer’s patch myeloid cells infection by <i>Listeria</i> signals through gp38+ stromal cells and locks intestinal villus invasion

Disson, Olivier; Blériot, Camille; Jacob, James R.; Serafini, Nicolas; Dulauroy, Sophie; Jouvion, Grégory; Fèvre, Cindy; Gessain, Grégoire; Thouvénot, Pierre; Eberl, Gérard; Santo, James P. Di; Peduto, Lucie; Lecuit, Marc

doi:10.1084/jem.20181210

Cited by 34 publications

(32 citation statements)

References 97 publications

(137 reference statements)

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“…Taken together, these results suggest that sensing the presence of a pathogen triggers robust colonic responses, which might potentially be a preparatory mechanism in case of pathogenic expansion. Indeed, early proliferation and STAT3 activation have recently been seen in the small intestine following Listeria monocytogenes mouse infection (47).…”

Section: Discussionmentioning

confidence: 99%

Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic Citrobacter rodentium Infection

Hopkins

Roumeliotis

Mullineaux-Sanders

et al. 2019

mBio

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We used the mouse attaching and effacing (A/E) pathogen Citrobacter rodentium, which models the human A/E pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli (EPEC and EHEC), to temporally resolve intestinal epithelial cell (IEC) responses and changes to the microbiome during in vivo infection. We found the host to be unresponsive during the first 3 days postinfection (DPI), when C. rodentium resides in the caecum. In contrast, at 4 DPI, the day of colonic colonization, despite only sporadic adhesion to the apex of the crypt, we observed robust upregulation of cell cycle and DNA repair processes, which were associated with expansion of the crypt Ki67-positive replicative zone, and downregulation of multiple metabolic processes (including the tricarboxylic acid [TCA] cycle and oxidative phosphorylation). Moreover, we observed dramatic depletion of goblet and deep crypt secretory cells and an atypical regulation of cholesterol homeostasis in IECs during early infection, with simultaneous upregulation of cholesterol biogenesis (e.g., 3-hydroxy-3-methylglutaryl–coenzyme A reductase [Hmgcr]), import (e.g., low-density lipoprotein receptor [Ldlr]), and efflux (e.g., AbcA1). We also detected interleukin 22 (IL-22) responses in IECs (e.g., Reg3γ) on the day of colonic colonization, which occurred concomitantly with a bloom of commensal Enterobacteriaceae on the mucosal surface. These results unravel a new paradigm in host-pathogen-microbiome interactions, showing for the first time that sensing a small number of pathogenic bacteria triggers swift intrinsic changes to the IEC composition and function, in tandem with significant changes to the mucosa-associated microbiome, which parallel innate immune responses. IMPORTANCE The mouse pathogen C. rodentium is a widely used model for colonic infection and has been a major tool in fundamental discoveries in the fields of bacterial pathogenesis and mucosal immunology. Despite extensive studies probing acute C. rodentium infection, our understanding of the early stages preceding the infection climax remains relatively undetailed. To this end, we apply a multiomics approach to resolve temporal changes to the host and microbiome during early infection. Unexpectedly, we found immediate and dramatic responses occurring on the day of colonic infection, both in the host intestinal epithelial cells and in the microbiome. Our study suggests changes in cholesterol and carbon metabolism in epithelial cells are instantly induced upon pathogen detection in the colon, corresponding with a shift to primarily facultative anaerobes constituting the microbiome. This study contributes to our knowledge of disease pathogenesis and mechanisms of barrier regulation, which is required for development of novel therapeutics targeting the intestinal epithelium.

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Section: Discussionmentioning

confidence: 99%

Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic Citrobacter rodentium Infection

Hopkins

Roumeliotis

Mullineaux-Sanders

et al. 2019

mBio

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“…BLP prevents Lm from causing intestinal barrier loss by maintaining mucus-producing goblet cells and limiting epithelial apoptotic and proliferative cells. Lm crosses the intestinal villus epithelium during goblet cell (GC) exocytosis 33 and epithelial cell extrusion 35 and upon infection, Lm accelerates intestinal villus epithelium proliferation while decreasing the number of GCs 48 . However, the decrease in GCs is detrimental for the host since it reduces the thickness of the protective mucosal barrier 48 .…”

Section: Resultsmentioning

confidence: 99%

Receptor-targeted engineered probiotics mitigate lethal Listeria infection

et al. 2020

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Probiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillusprobiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-κB and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.

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“…Additionally, it has been implicated in modulating intestinal epithelial homeostasis by inducing acceleration of intestinal villus epithelium renewal and a decline in goblet cell numbers to lock down one potential portal of entry for L. monocytogenes . In an intestinal organoid-based model, it was demonstrated that for the induction of epithelial cell proliferation, phosphorylation of both signal transducer and activator of transcription (STAT) proteins STAT1 and STAT3 is mandatory [ 78 ]. Intriguingly, STAT1 and STAT3 appear to exert opposing cellular functions with regard to cell cycle regulation, survival signaling, and tumor immunity [ 79 ].…”

Section: Bacterial Enteropathogens and Their In Vitro mentioning

confidence: 99%

“…Intriguingly, STAT1 and STAT3 appear to exert opposing cellular functions with regard to cell cycle regulation, survival signaling, and tumor immunity [ 79 ]. In vitro activation of the respective STAT proteins could be elicited by incubation with IL 22 or IL 11, originally derived from the pericryptal subset of gp38+ stromal cells and IFN γ supplied by natural killer cells [ 78 ].…”

Section: Bacterial Enteropathogens and Their In Vitro mentioning

confidence: 99%

Enteropathogenic Infections: Organoids Go Bacterial

Hentschel

Arnold

Seufferlein

et al. 2021

Stem Cells International

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Enteric infections represent a major health care challenge which is particularly prevalent in countries with restricted access to clean water and sanitation and lacking personal hygiene precautions, altogether facilitating fecal-oral transmission of a heterogeneous spectrum of enteropathogenic microorganisms. Among these, bacterial species are responsible for a considerable proportion of illnesses, hospitalizations, and fatal cases, all of which have been continuously contributing to ignite researchers’ interest in further exploring their individual pathogenicity. Beyond the universally accepted animal models, intestinal organoids are increasingly valued for their ability to mimic key architectural and physiologic features of the native intestinal mucosa. As a consequence, they are regarded as the most versatile and naturalistic in vitro model of the gut, allowing monitoring of adherence, invasion, intracellular trafficking, and propagation as well as repurposing components of the host cell equipment. At the same time, infected intestinal organoids allow close characterization of the host epithelium’s immune response to enteropathogens. In this review, (i) we provide a profound update on intestinal organoid-based tissue engineering, (ii) we report the latest pathophysiological findings defining the infected intestinal organoids, and (iii) we discuss the advantages and limitations of this in vitro model.

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Peyer’s patch myeloid cells infection by Listeria signals through gp38+ stromal cells and locks intestinal villus invasion

Cited by 34 publications

References 97 publications

Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic Citrobacter rodentium Infection

Intestinal Epithelial Cells and the Microbiome Undergo Swift Reprogramming at the Inception of Colonic Citrobacter rodentium Infection

Receptor-targeted engineered probiotics mitigate lethal Listeria infection

Enteropathogenic Infections: Organoids Go Bacterial

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