Commensal bacteria promote type I interferon signaling to maintain immune tolerance

Abstract

Type I interferons (IFN) play essential roles in numerous physiological processes, acting as central coordinators in the host response against pathogens. Upon sensing of microbial ligands, host cells rapidly activate the type I IFN response to prime innate and adaptive immune responses. Recent studies suggest tonic IFN are maintained by commensal microbes and critical in mounting an effective immune response to viral pathogens. Further, emerging developments have extended an immunoregulatory role of type I IFN in the maintenance of immune homeostasis. Yet whether immunomodulatory bacteria from the gut microbiota operate through IFN signaling to promote immune tolerance remains largely unanswered. Here we show that commensal microbes are necessary to maintain type I IFN responses in intestinal tissues. Specifically, Bacteroides fragilis induced type I IFN response in dendritic cells (DCs) and this pathway is necessary for the induction of IL-10-producing Foxp3+ regulatory T cells (Tregs). In addition, we show upregulation of type I IFN related genes in Tregs from mesenteric lymph nodes and colonic lamina propria of mice colonized with B. fragilis. Our findings demonstrate type I interferon signaling plays an important role in microbiota-mediated immune tolerance in the gut.

The gut microbiota and its metabolite butyrate shape metabolism and antiviral immunity along the gut-lung axis in the chicken

“…Our investigation revealed significant alterations in gene expression signatures due to the absence of a GM in the chicken. In caeca, lungs, and spleen of GF chickens, we observed a substantial reduction in the expression of ISGs, such as IRF1, IFIT, OASL, and MX1, aligning with findings in GF mice 74 .…”

Neonatal Peyer’s patch cDC activation as a pacemaker of postnatal immune maturation

“…This also includes the IFN gene expression profile in DC (Stefan et al, 2020). Interestingly, some bacterial taxa might harbor a particularly strong ISG inducing activity such as lactobacilli, Blautia coccidioides and the anaerobic commensal bacteria of the Bacteroides species (Ayala, 2021;Kawashima et al, 2018;Kawashima et al, 2013;Stefan et al, 2020;Yang et al, 2021). In our dataset, Bacteroides spp.…”

Immunomodulatory Role of Interferons in Viral and Bacterial Infections

“…The reasons for such diverse roles of type I IFN in bacterial infections are still unclear and require many interdisciplinary studies. Based on research, scientists have shown that bacteria trigger the production of type I IFN mainly by recognizing their nucleic acids or lipopolysaccharide (LPS), which is one of the components of the cell wall [263][264][265]. As a result of the recognition of these PAMPs, innate immune response mechanisms are activated.…”

“…As a result of the recognition of these PAMPs, innate immune response mechanisms are activated. The activation pathways of IFN induction mechanisms have been best described for IFN-β, which, according to studies, is among Based on research, scientists have shown that bacteria trigger the production of type I IFN mainly by recognizing their nucleic acids or lipopolysaccharide (LPS), which is one of the components of the cell wall [263][264][265]. As a result of the recognition of these PAMPs, innate immune response mechanisms are activated.…”