Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons-Reference-Cited by-同舟云学术

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

Published:2021-06-21 Issue: Volume:10 Page:
ISSN:2050-084X
Container-title:eLife
language:en
Short-container-title:

Author:

Ji Daisy X¹,Witt Kristen C¹^ORCID,Kotov Dmitri I¹^ORCID,Margolis Shally R¹,Louie Alexander¹,Chevée Victoria²,Chen Katherine J¹,Gaidt Moritz¹,Dhaliwal Harmandeep S³,Lee Angus Y⁴,Nishimura Stephen L⁵,Zamboni Dario S⁶^ORCID,Kramnik Igor⁷^ORCID,A. Portnoy Daniel³,Darwin K Heran⁸,Vance Russell E⁹^ORCID

Affiliation:

1. Molecular and Cell Biology, UC Berkeley, Berkeley, United States

2. Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States

3. Cancer Research Laboratory, UC Berkeley, Berkeley, United States

4. Department of Molecular & Cell Biology, University of California, Berkeley, Berkeley, United States

5. Pathology, University of California at San Francisco, San Francisco, United States

6. Cell Biology, University of São Paulo, Ribeirão Preto, Brazil

7. The National Emerging Infectious Diseases Laboratories, Department of Medicine, Boston University, Boston University School of Medicine, Boston, United States

8. Department of Microbiology, New York University Robert Grossman School of Medicine, New York, United States

9. Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, 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.

Funder

National Institutes of Health

Howard Hughes Medical Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Link

https://cdn.elifesciences.org/articles/67290/elife-67290-v1.pdf

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