An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes

Listeria monocytogenes causes severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that du...

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Autores principales:	Natalie Descoeudres, Luc Jouneau, Céline Henry, Kevin Gorrichon, Aurélie Derré-Bobillot, Pascale Serror, Laura Lee Gillespie, Cristel Archambaud, Alessandro Pagliuso, Hélène Bierne
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Listeria monocytogenes liver acute phase response interferon persistence innate immunity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/5865eb16aaa9446196923ba1e95bafbe
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spelling	oai:doaj.org-article:5865eb16aaa9446196923ba1e95bafbe2021-11-10T06:49:52ZAn Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes2235-298810.3389/fcimb.2021.761945https://doaj.org/article/5865eb16aaa9446196923ba1e95bafbe2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.761945/fullhttps://doaj.org/toc/2235-2988Listeria monocytogenes causes severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that during long-term infection of hepatocytes, a subpopulation of Listeria may escape eradication by entering a persistence phase in intracellular vacuoles. Here, we examine whether this long-term infection alters hepatocyte defense pathways, which may be instrumental for bacterial persistence. We first optimized cell models of persistent infection in human hepatocyte cell lines HepG2 and Huh7 and primary mouse hepatocytes (PMH). In these cells, Listeria efficiently entered the persistence phase after three days of infection, while inducing a potent interferon response, of type I in PMH and type III in HepG2, while Huh7 remained unresponsive. RNA-sequencing analysis identified a common signature of long-term Listeria infection characterized by the overexpression of a set of genes involved in antiviral immunity and the under-expression of many acute phase protein (APP) genes, particularly involved in the complement and coagulation systems. Infection also altered the expression of cholesterol metabolism-associated genes in HepG2 and Huh7 cells. The decrease in APP transcripts was correlated with lower protein abundance in the secretome of infected cells, as shown by proteomics, and also occurred in the presence of APP inducers (IL-6 or IL-1β). Collectively, these results reveal that long-term infection with Listeria profoundly deregulates the innate immune functions of hepatocytes, which could generate an environment favorable to the establishment of persistent infection.Natalie DescoeudresLuc JouneauCéline HenryKevin GorrichonAurélie Derré-BobillotPascale SerrorLaura Lee GillespieCristel ArchambaudAlessandro PagliusoHélène BierneFrontiers Media S.A.articleListeria monocytogenesliveracute phase responseinterferonpersistenceinnate immunityMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Listeria monocytogenes liver acute phase response interferon persistence innate immunity Microbiology QR1-502
spellingShingle	Listeria monocytogenes liver acute phase response interferon persistence innate immunity Microbiology QR1-502 Natalie Descoeudres Luc Jouneau Céline Henry Kevin Gorrichon Aurélie Derré-Bobillot Pascale Serror Laura Lee Gillespie Cristel Archambaud Alessandro Pagliuso Hélène Bierne An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes
description	Listeria monocytogenes causes severe foodborne illness in pregnant women and immunocompromised individuals. After the intestinal phase of infection, the liver plays a central role in the clearance of this pathogen through its important functions in immunity. However, recent evidence suggests that during long-term infection of hepatocytes, a subpopulation of Listeria may escape eradication by entering a persistence phase in intracellular vacuoles. Here, we examine whether this long-term infection alters hepatocyte defense pathways, which may be instrumental for bacterial persistence. We first optimized cell models of persistent infection in human hepatocyte cell lines HepG2 and Huh7 and primary mouse hepatocytes (PMH). In these cells, Listeria efficiently entered the persistence phase after three days of infection, while inducing a potent interferon response, of type I in PMH and type III in HepG2, while Huh7 remained unresponsive. RNA-sequencing analysis identified a common signature of long-term Listeria infection characterized by the overexpression of a set of genes involved in antiviral immunity and the under-expression of many acute phase protein (APP) genes, particularly involved in the complement and coagulation systems. Infection also altered the expression of cholesterol metabolism-associated genes in HepG2 and Huh7 cells. The decrease in APP transcripts was correlated with lower protein abundance in the secretome of infected cells, as shown by proteomics, and also occurred in the presence of APP inducers (IL-6 or IL-1β). Collectively, these results reveal that long-term infection with Listeria profoundly deregulates the innate immune functions of hepatocytes, which could generate an environment favorable to the establishment of persistent infection.
format	article
author	Natalie Descoeudres Luc Jouneau Céline Henry Kevin Gorrichon Aurélie Derré-Bobillot Pascale Serror Laura Lee Gillespie Cristel Archambaud Alessandro Pagliuso Hélène Bierne
author_facet	Natalie Descoeudres Luc Jouneau Céline Henry Kevin Gorrichon Aurélie Derré-Bobillot Pascale Serror Laura Lee Gillespie Cristel Archambaud Alessandro Pagliuso Hélène Bierne
author_sort	Natalie Descoeudres
title	An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes
title_short	An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes
title_full	An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes
title_fullStr	An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes
title_full_unstemmed	An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes
title_sort	immunomodulatory transcriptional signature associated with persistent listeria infection in hepatocytes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/5865eb16aaa9446196923ba1e95bafbe
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An Immunomodulatory Transcriptional Signature Associated With Persistent Listeria Infection in Hepatocytes

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