Table 2.
Role of type I interferons (IFN) in intestinal inflammation and bacterial infections.
| Mouse strain | Phenotype—type I IFN | Reference |
|---|---|---|
| BACTERIAL INFECTION | ||
| Listeria monocytogenes | ||
| IFNAR1−/−-, IFN-β−/−, IRF-3−/−, IRF-7−/− | Type I IFN signaling is detrimental during systemic infection | (25, 62–64) |
| IFNAR1−/− | Kernbauer et al. showed that type I IFN signaling during oral infection with the potent type I IFN inducing LO28 strain is beneficial for the host. By contrast, Pitts et al. did not observe any role for type I IFN during oral infection with the EGDe strain | (65, 66) |
| LysM-Cre IFNARfl/fl | Lack of IFN signaling in LysM+ cells confers protection during systemic infection most pronounced in early infectious stages | (25) |
| Salmonella Typhimurium | ||
| IFN-β−/− | Lack of IFN-β mediates increased resistance to lethality during oral S. Typhimurium infection | (67) |
| IFNAR−/− | IFNAR deficiency leads to increased resistance to oral S. Typhimurium characterized by decreased bacterial spread and weight loss but similar intestinal pathology. In accordance, type I IFN induction due to influenza coinfection exacerbates the disease and CFU but decreased intestinal immunopathology | (68) |
| USP18−/− | During Salmonella infection, Usp18-mutant mice are more susceptible to systemic (i.e., typhoid) S. Typhimurium infection. By contrast, in the streptomycin-induced model of typhlocolitis, mutant Usp18 mice display lower pathology scores, low IFN-γ production but upregulated type I IFN signaling compared to control mice, resulting in earlier systemic dissemination of the bacteria and decreased survival | (69) |
| Yersinia enterocolitica | ||
| TRIF−/− | IFN-β treatment protects TRIF−/− mice from Y. enterocolitica lethality | (70) |
| COLITIS MODELS | ||
| T cell transfer colitis | ||
| IFN-α treatment | Ameliorates T cell transfer colitis | (71) |
| IFNAR−/−host | IFNAR deficiency in the host cells exacerbates colitis; indirect effect on maintenance of Foxp3+ Tregs | (23) |
| IFNAR−/− T cells | Induction of colitis by IFNAR−/− T cells similar to wt T cells, however, boosting type I IFN by poly(I:C) treatment attenuates T cell transfer colitis in a T cell-(IFNAR-)dependent manner | (23, 72) |
| IFNAR−/− Tregs | Conflicting findings on the role of IFNAR signaling in Tregs for protection from T cell transfer colitis | (23, 71) |
| Dextran sodium sulfate (DSS) colitis | ||
| CpG ODN treatment | CpG ODN protects against DSS colitis in an IFNAR-dependent manner; by contrast, La-IFN-β treatment exacerbates colitis | (73, 74) |
| IFN-β-expressing Lactobacillus (La-IFN-β) | ||
| IFNAR1−/− | Type I IFN signaling suppress acute DSS colitis but delays the resolution | (73, 75) |
| Villin-Cre IFNAR1fl/fl | IFNAR deficiency in intestinal epithelial cells results in similar susceptibility to DSS colitis as wt; increased tumor burden in DSS + azoxymethane model (due to microbiota alterations) | (76) |
| IL-28Rα−/− | Increased susceptibility in IL-28Rα−/−, same as IL-28Rα−/− IFNAR1−/− DKO indicating dominant role of type III IFN | (77) |