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Cell Host Microbe. 2017 Jun 14;21(6):682-694.e5. doi: 10.1016/j.chom.2017.05.005.

Enhancement of IFNγ Production by Distinct Commensals Ameliorates Salmonella-Induced Disease.

Author information

1
Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
2
Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany.
3
Department of Microbial Pathogenesis and Microbial Sciences Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
4
Institute for Experimental Infection Research, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover Medical School and the Helmholtz Centre for Infection Research, 30625 Hannover, Germany.
5
Department of Immunobiology, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
6
Research Group Infection Biology of Salmonella, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany.
7
Research Group Microbial Immune Regulation, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany. Electronic address: till.strowig@helmholtz-hzi.de.

Abstract

The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease induced by enteric Salmonella Typhimurium infection is strongly modulated by microbiota composition in individual lines. Transferring a restricted community of cultivable intestinal commensals from protected into susceptible mice decreases S. Typhimurium tissue colonization and consequently disease severity. This reduced tissue colonization, along with ameliorated weight loss and prolonged survival, depends on microbiota-enhanced IFNγ production, as IFNγ-deficient mice do not exhibit protective effects. Innate cells and CD4+ T cells increase in number and show high levels of IFNγ after transfer of the commensal community. Thus, distinct microbiota members prevent intestinal Salmonella infection by enhancing antibacterial IFNγ responses.

KEYWORDS:

16S rRNA sequencing; CD4(+) T cells; IFNγ; Salmonella Typhimurium; bacterial cultivation; colonization resistance; enteric infections; intestinal microbiota

PMID:
28618267
DOI:
10.1016/j.chom.2017.05.005
[Indexed for MEDLINE]
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