Commensal bacteria promote type I interferon signalling to maintain immune tolerance 

Vasques Ayala et al. (BioRxiv) doi: 10.1101/2021.10.21.464743

Keywords

  • Microbiota        

  • Tolerance

  • Interferon

 

Main Findings

Intestinal DCs produce and maintain a tonic type I IFN responses upon sensing of gut microbiota (Kole et al. J Imm 2013; Schaupp et al. Cell 2020) and this microbiota-induced IFN response has been found crucial when mounting an effective antiviral response (Stefan et al. Cell 2020; Bradley et al. Cell Rep 2019). Also, commensal-primed DCs have been shown to promote Treg responses (Shen et al. Cell Host Microbe 2012; Chu et al. Science 2016). 

In this preprint, Vasques Ayala et al. nicely link the microbiota-induced tonic type I INF response in DCs with the generation of immune tolerance in the gut. They analysed the contribution of gut microbiota in maintaining a tonic type I IFN responses in mucosal tissue using B. fragilis as a model for commensal bacteria. B. fragilis had been previously shown to be sensed via TLR2 and NOD2 in DCs to promote Treg responses (Shen et al. Cell Host Microbe 2012; Chu et al. Science 2016).  The authors found that B. fragilis induced IFNß in DCs and promoted autocrine IFN signalling, suggesting that the previously found B. fragilis-mediated immune tolerance is in part achieved via IFN. Also, they found that B. fragilis-pulsed DCs induced IL-10-Tregs via IFNß. This appeared to be through Ifnar1 in DCs and suggested to be regulated also downstream, as B. fragilis induced selectively the expression of certain ISGs. 

To further explore, they performed an sc-RNAseq in intestinal Tregs in mesenteric lymph nodes and in the colon lamina propria and found an association between bacterial colonisation and an IFN gene signature in gut Tregs. 

Altogether, this preprint highlights the immunoregulatory role for IFN in the gut induced by commensal bacteria. 

Limitations

 

  • The study is limited to their chosen model for commensal bacteria. 

  • The study would be more complete if it could check the contribution of auto/paracrine effects of IL-10 in the induction of Tregs.

  • Also, in line with previously published work, the study would benefit if the authors explored the involvement of TLR2 and NOD2 sensing pathways and whether they would be sufficient to induce tolerance.  

  • The induction of IFN and Tregs by B. fragilis is done in BMDCs, it would be informative to comment on the possible bias of these DCs to gut DCs. 

Significance/Novelty

 

Vasques Ayala et al. explore the importance of microbial-induced IFN in the generation of immune tolerance. The authors found that tonic IFNß induced in DCs by commensal bacteria is directly involved in the induction of IL-10-producing Foxp3+ T regs. This study contributes to the understanding on the immunoregulatory role for gut microbiota by correlating it to a tonic IFN response.

Credit

Reviewed by Ester Gea-Mallorquí as part of the cross-institutional journal club of the Immunology Institute of the Icahn School of Medicine, Mount Sinai, the Kennedy Institute of Rheumatology and the Oxford Centre for Immuno-Oncology  (OXCIO) (University of Oxford, GB) and Karolinska Institute’s Center for Infectious Medicine (CIM) & Center for Molecular Medicine (CMM). Follow her on Twitter.