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

eLife

Angus Y Lee¹  Harmandeep S Dhaliwal¹  Dario S Zamboni²  K Heran Darwin³  Stephen L Nishimura⁴  Daisy X Ji⁵  Shally R Margolis⁵  Kristen C Witt⁵  Moritz M Gaidt⁵  Alexander Louie⁵  Victoria Chevée⁵  Daniel A Portnoy⁶  Katherine J Chen⁷  Dmitri I Kotov⁷  Russell E Vance⁸  Igor Kramnik⁹ 

[1] Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States;Department of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil;Department of Microbiology, New York University Grossman School of Medicine, New York, United States;Department of Pathology, University of California, San Francisco, San Francisco, United States;Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Department of Plant and Microbial Biology, University of California, Berkeley, Berkeley, United States;Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States;Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States;Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, United States;Cancer Research Laboratory, University of California, Berkeley, Berkeley, United States;The National Emerging Infectious Diseases Laboratory, Department of Medicine (Pulmonary Center), and Department of Microbiology, Boston University School of Medicine, Boston, United States;

关键词: mycobacterium tuberculosis;    legionella pneumophila;    type i interferon;    Mouse;   

DOI  :  10.7554/eLife.67290

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY