Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons
- UC Berkeley, United States
- University of California, Berkeley, United States
- University of California at San Francisco, United States
- University of São Paulo, Brazil
- Boston University, Boston University School of Medicine, United States
- New York University Robert Grossman School of Medicine, United States
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.
Data availability
RNA-seq data is available at GEO, accession number GSE166114. Amplicon sequencing data is available at the SRA, BioProject accession number PRJNA698382
Article and author information
Author details
Funding
National Institutes of Health (R37AI075039)
- Russell E Vance
National Institutes of Health (R01AI155634)
- Russell E Vance
Howard Hughes Medical Institute (Investigator Award)
- Russell E Vance
National Institutes of Health (P01AI066302)
- Russell E Vance
National Institutes of Health (P01AI066302)
- Daniel A. Portnoy
National Institutes of Health (R01HL134183)
- Stephen L Nishimura
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Christina L Stallings, Washington University School of Medicine, United States
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. Animal studies were approved by the UC Berkeley Animal Care and Use Committee (current protocol number: AUP-2014-09-6665-2).
Version history
- Received: February 6, 2021
- Accepted: June 20, 2021
- Accepted Manuscript published: June 21, 2021 (version 1)
- Version of Record published: July 1, 2021 (version 2)
Copyright
© 2021, Ji et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons
eLife 10:e67290.
https://doi.org/10.7554/eLife.67290
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