Research is increasingly showing the wide-ranging influence of the microbiome on immune responses and health. A collection of recent reports provide a peek into the varied molecular mediators of the microbial influence on immune responses (Science http://dx.doi.org/10.1126/science.1241165; Immunity 38, 1187–1197; Immunity 38, 1198–1210; Immunity 38, 1211–1222).

Patrick Smith et al. asked what bacterial products can regulate colonic regulatory T (Treg) cells. The researchers found that short-chain fatty acids, which are bacterial fermentation products, could trigger the proliferation of and enhance the function of interleukin-10–producing inducible Treg cells in mice. These fatty acids, acting through their receptor GRP43, inhibited histone deacetylase expression, thus increasing histone acetylation in colonic Treg cells, which may account for their effects.

Tadaomi Kawashima et al. sought to understand the role of Toll-like receptors (TLRs) in the recognition of lactic acid bacteria by immune cells, as these bacteria have been shown to promote beneficial immune responses against pathogens and suppress colitis in mice. The authors found that lactic acid bacteria potently induce the production of interferon-β (IFN-β)—which is important in antiviral immunity—by bone marrow–derived dendritic cells. In contrast, pathogenic bacteria were less effective at inducing this response. Bacterial double-stranded RNA was responsible for triggering TLR3 activation and IFN-β production and mediating the anti-inflammatory effects of lactic acid bacteria in mice. The researchers found that commensal bacteria produced higher amounts of double-stranded RNA than pathogenic species, accounting for the differential induction of IFN-β.

The studies add to our understanding of how bacterial products can modulate different components of the immune system to collectively reduce inflammation and potentially facilitate responses to microbial pathogens.