RT Journal Article
SR Electronic
T1 Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.01.07.897553
DO 10.1101/2020.01.07.897553
A1 Daisy X. Ji
A1 Kristen C. Witt
A1 Dmitri I. Kotov
A1 Shally R. Margolis
A1 Alexander Louie
A1 Katherine J. Chen
A1 Harmandeep S. Dhaliwal
A1 Angus Y. Lee
A1 Dario S. Zamboni
A1 Igor Kramnik
A1 Daniel A. Portnoy
A1 K. Heran Darwin
A1 Russell E. Vance
YR 2020
UL http://biorxiv.org/content/early/2020/01/08/2020.01.07.897553.abstract
AB Type I interferons (IFNs) are essential for anti-viral immunity, but often impair protective immune responses during bacterial infections. How type I IFNs are strongly induced during viral infections, and yet are appropriately restrained during bacterial infections, remains poorly understood. The Super susceptibility to tuberculosis 1 (Sst1) locus in mice confers resistance to many bacterial infections. Here we provide evidence that Sp140 is a gene encoded within the Sst1 locus that functions to repress the expression of type I IFNs during bacterial infections. We generated Sp140−/− mice and find they are susceptible to infection by diverse bacteria, including Listeria monocytogenes, 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 repressor of type I IFNs that is essential for resistance to bacterial infections.