Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons.

Type I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. An important question is how type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections. The () locus in mice confers resistance to diverse bacterial infections. Here we provide evidence that is a gene encoded within the locus that represses type I IFN transcription during bacterial infections. We generated mice and found that they are susceptible to infection by and . Susceptibility of mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (). Our results implicate as an important negative regulator of type I IFNs that is essential for resistance to bacterial infections.