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

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