Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons

Daisy X. Ji; Kristen C. Witt; Dmitri I. Kotov; Shally R. Margolis; Alexander Louie; Victoria Chevée; Katherine J. Chen; Moritz M. Gaidt; Harmandeep S. Dhaliwal; Angus Y. Lee; Stephen L. Nishimura; Dario S. Zamboni; Igor Kramnik; Daniel A. Portnoy; K. Heran Darwin; Russell E. Vance

doi:10.7554/eLife.67290

Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons

Daisy X. Ji, Kristen C. Witt, Dmitri I. Kotov, Shally R. Margolis, Alexander Louie, Victoria Chevée, Katherine J. Chen, Moritz M. Gaidt, Harmandeep S. Dhaliwal, Angus Y. Lee, Stephen L. Nishimura, Dario S. Zamboni, Igor Kramnik, Daniel A. Portnoy, K. Heran Darwin, Russell E. Vance

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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.

Original language	English
Article number	e67290
Journal	eLife
Volume	10
DOIs	https://doi.org/10.7554/eLife.67290
State	Published - Jun 2021

Access to Document

10.7554/eLife.67290

Cite this

Ji, D. X., Witt, K. C., Kotov, D. I., Margolis, S. R., Louie, A., Chevée, V., Chen, K. J., Gaidt, M. M., Dhaliwal, H. S., Lee, A. Y., Nishimura, S. L., Zamboni, D. S., Kramnik, I., Portnoy, D. A., Darwin, K. H., & Vance, R. E. (2021). Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons. eLife, 10, Article e67290. https://doi.org/10.7554/eLife.67290

@article{3e8e012f932741948ac75340a6726f26,

title = "Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons",

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.",

author = "Ji, {Daisy X.} and Witt, {Kristen C.} and Kotov, {Dmitri I.} and Margolis, {Shally R.} and Alexander Louie and Victoria Chev{\'e}e and Chen, {Katherine J.} and Gaidt, {Moritz M.} and Dhaliwal, {Harmandeep S.} and Lee, {Angus Y.} and Nishimura, {Stephen L.} and Zamboni, {Dario S.} and Igor Kramnik and Portnoy, {Daniel A.} and Darwin, {K. Heran} and Vance, {Russell E.}",

year = "2021",

month = jun,

doi = "10.7554/eLife.67290",

language = "English",

volume = "10",

journal = "eLife",

issn = "2050-084X",

}

Ji, DX, Witt, KC, Kotov, DI, Margolis, SR, Louie, A, Chevée, V, Chen, KJ, Gaidt, MM, Dhaliwal, HS, Lee, AY, Nishimura, SL, Zamboni, DS, Kramnik, I, Portnoy, DA, Darwin, KH & Vance, RE 2021, 'Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons', eLife, vol. 10, e67290. https://doi.org/10.7554/eLife.67290

TY - JOUR

T1 - Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons

AU - Ji, Daisy X.

AU - Witt, Kristen C.

AU - Kotov, Dmitri I.

AU - Margolis, Shally R.

AU - Louie, Alexander

AU - Chevée, Victoria

AU - Chen, Katherine J.

AU - Gaidt, Moritz M.

AU - Dhaliwal, Harmandeep S.

AU - Lee, Angus Y.

AU - Nishimura, Stephen L.

AU - Zamboni, Dario S.

AU - Kramnik, Igor

AU - Portnoy, Daniel A.

AU - Darwin, K. Heran

AU - Vance, Russell E.

PY - 2021/6

Y1 - 2021/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85108886873&partnerID=8YFLogxK

U2 - 10.7554/eLife.67290

DO - 10.7554/eLife.67290

M3 - Article

C2 - 34151776

AN - SCOPUS:85108886873

SN - 2050-084X

VL - 10

JO - eLife

JF - eLife

M1 - e67290

ER -

Role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons

Abstract

Access to Document

Other files and links

Fingerprint

Cite this