Listeria monocytogenes Establishes Commensalism in Germ-Free Mice Through the Reversible Downregulation of Virulence Gene Expression

Kyungjin Cho,Eunju O,Charles D Surh,Kwang Soon Kim,Sin-Hyeog Im,Darina Spasova,Sung-Wook Hong

doi:10.3389/fimmu.2021.666088

Abstract

The intestine harbors a complex community of bacterial species collectively known as commensal microbiota. Specific species of resident bacteria, as known as pathobiont, have pathogenic potential and can induce apparent damage to the host and intestinal inflammation in a certain condition. However, the host immune factors that permit its commensalism under steady state conditions are not clearly understood. Here, we studied the gut fitness of Listeria monocytogenes by using germ-free (GF) mice orally infected with this food-borne pathogen. L. monocytogenes persistently exists in the gut of GF mice without inducing chronic immunopathology. L. monocytogenes at the late phase of infection is not capable of infiltrating through the intestinal barrier. L. monocytogenes established the commensalism through the reversible down regulation of virulence gene expression. CD8+ T cells were found to be sufficient for the commensalism of L. monocytogenes. CD8+ T cells responding to L. monocytogenes contributed to the down-regulation of virulence gene expression. Our data provide important insights into the host-microbe interaction and have implications for developing therapeutics against immune disorders induced by intestinal pathogens or pathobionts.

Highlights

Multicellular organisms have co-evolved with a complex community of microbial species, collectively known as the commensal microbiota [1]
These results suggest that GF mice are capable of eliminating tissue-infiltrating L. monocytogenes as efficiently as specific pathogen-free (SPF) mice despite the persistent presence of luminal L. monocytogenes
To elucidate whether L. monocytogenes contributes to the intestinal barrier functions mediated by antimicrobial protein (AMP) as an effector arm of innate immunity, we examined the alteration of gene expression programs in intestinal epithelial cells (IECs) upon the oral infection with L. monocytogenes in GF mice by RNA sequencing analyses on FACSsorted CD45− Epcam+ IECs

Summary

Introduction

Multicellular organisms have co-evolved with a complex community of microbial species, collectively known as the commensal microbiota [1]. Gut fitness of pathogenic fungal or bacterial species can result from the evolutionary loss of virulence genes or from the reversible suppression of virulence gene expression in the gut [4,5,6] In the latter case, the bacterial species still possess a pathogenic potential, termed pathobionts, and are involved in the pathogenesis of intestinal infection or inflammatory bowel diseases [7, 8]. IgG specific to virulence factors, which are encoded by the locus of enterocyte effacement (LEE), eliminates virulent bacteria in the gut [9] It is still unclear whether other intestinal pathogens can establish commensalism within the host and whether host-derived factors, other than antibodies, can promote commensalism

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Conclusion