- Ji, Daisy X;
- Witt, Kristen C;
- Kotov, Dmitri I;
- Margolis, Shally R;
- Louie, Alexander;
- Chevée, Victoria;
- Chen, Katherine J;
- Gaidt, Moritz;
- Dhaliwal, Harmandeep S;
- Lee, Angus Y;
- Nishimura, Stephen L;
- Zamboni, Dario S;
- Kramnik, Igor;
- Portnoy, Daniel A;
- Darwin, K Heran;
- Vance, Russell E
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 found that 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.