Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons
Open Access
- 21 June 2021
- journal article
- research article
- Published by eLife Sciences Publications, Ltd in eLife
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 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.Keywords
Funding Information
- National Institutes of Health (R37AI075039)
- National Institutes of Health (R01AI155634)
- Howard Hughes Medical Institute (Investigator Award)
- National Institutes of Health (P01AI066302)
- National Institutes of Health (R01HL134183)
- Burroughs Wellcome Fund
This publication has 57 references indexed in Scilit:
- The sst1 Resistance Locus Regulates Evasion of Type I Interferon Signaling by Chlamydia pneumoniae as a Disease Tolerance MechanismPLoS Pathogens, 2013
- One-Step Generation of Mice Carrying Mutations in Multiple Genes by CRISPR/Cas-Mediated Genome EngineeringCell, 2013
- Host-microbe interactions have shaped the genetic architecture of inflammatory bowel diseaseNature, 2012
- Mouse Model of Necrotic Tuberculosis Granulomas Develops Hypoxic LesionsThe Journal of Infectious Diseases, 2011
- Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility lociNature Genetics, 2010
- Induction of IFN-αβ enables Listeria monocytogenes to suppress macrophage activation by IFN-γThe Journal of Experimental Medicine, 2010
- The Sequence Alignment/Map format and SAMtoolsBioinformatics, 2009
- Fast and accurate short read alignment with Burrows–Wheeler transformBioinformatics, 2009
- Variants in the SP110 gene are associated with genetic susceptibility to tuberculosis in West AfricaProceedings of the National Academy of Sciences of the United States of America, 2006
- No associations of human pulmonary tuberculosis with Sp110 variantsJournal of Medical Genetics, 2005