4.7 Article

Commensal microbes provide first line defense against Listeria monocytogenes infection

期刊

JOURNAL OF EXPERIMENTAL MEDICINE
卷 214, 期 7, 页码 1973-1989

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ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20170495

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资金

  1. National Institutes of Health [K23 AI095398-01, RO1 AI42135, U01 AI124275-01, P30 CA008748]
  2. Lucille Castori Center for Microbes, Inflammation, and Cancer
  3. Tow Foundation grant
  4. Swiss National Science Foundation Early Postdoc Mobility Fellowship
  5. Cancer Research Institute

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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 immuno-deficient 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.

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