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

Abstract

Abstract 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 Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to diverse bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that represses type I IFN transcription during bacterial infections. We generated Sp140 -/- mice and find they are susceptible to infection by Legionella pneumophila and Mycobacterium tuberculosis. Susceptibility of Sp140 -/- mice to bacterial infection was rescued by crosses to mice lacking the type I IFN receptor (Ifnar -/- ). Our results implicate Sp140 as an important negative regulator of type I IFNs that is essential for resistance to bacterial infections. Impact Statement Repression of type I interferons by SP140 is essential for resistance to Legionella pneumophila and Mycobacterium tuberculosis .