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

Publication date: 14 June 2017
Source:Cell Host & Microbe, Volume 21, Issue 6
Author(s): Sophie Thiemann, Nathiana Smit, Urmi Roy, Till Robin Lesker, Eric J.C. Gálvez, Julia Helmecke, Marijana Basic, Andre Bleich, Andrew L. Goodman, Ulrich Kalinke, Richard A. Flavell, Marc Erhardt, Till Strowig
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.

Graphical abstract

Teaser

The microbiota contributes to colonization resistance against invading pathogens. Thiemann et al. determine that intestinal microbiota ameliorates acute Salmonella-induced diarrhea by priming the immune system and preventing tissue invasion. This is achieved by enhancing antibacterial IFNγ production by innate cells and CD4⁺ T cells during infection.


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