Commensal microbes provide first line defense against Listeria monocytogenes infection

Author:

Becattini Simone1ORCID,Littmann Eric R.2,Carter Rebecca A.1ORCID,Kim Sohn G.1,Morjaria Sejal M.3,Ling Lilan2,Gyaltshen Yangtsho2,Fontana Emily2ORCID,Taur Ying23,Leiner Ingrid M.1,Pamer Eric G.123ORCID

Affiliation:

1. Immunology Program, Sloan Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, NY

2. Lucille Castori Center for Microbes Inflammation and Cancer, Molecular Microbiology Core Facility, Memorial Sloan-Kettering Cancer Center, New York, NY

3. Infectious Diseases Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY

Abstract

Listeria monocytogenes is a foodborne pathogen that causes septicemia, meningitis and chorioamnionitis and is associated with high mortality. Immunocompetent humans and animals, however, can tolerate high doses of L. monocytogenes without developing systemic disease. The intestinal microbiota provides colonization resistance against many orally acquired pathogens, and antibiotic-mediated depletion of the microbiota reduces host resistance to infection. Here we show that a diverse microbiota markedly reduces Listeria monocytogenes colonization of the gut lumen and prevents systemic dissemination. Antibiotic administration to mice before low dose oral inoculation increases L. monocytogenes growth in the intestine. In immunodeficient or chemotherapy-treated mice, the intestinal microbiota provides nonredundant defense against lethal, disseminated infection. We have assembled a consortium of commensal bacteria belonging to the Clostridiales order, which exerts in vitro antilisterial activity and confers in vivo resistance upon transfer into germ free mice. Thus, we demonstrate a defensive role of the gut microbiota against Listeria monocytogenes infection and identify intestinal commensal species that, by enhancing resistance against this pathogen, represent potential probiotics.

Funder

National Institutes of Health

Lucille Castori Center for Microbes, Inflammation, and Cancer

Tow Foundation

Swiss National Science Foundation

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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