Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons
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 Supe...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2021-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/67290 |
| _version_ | 1811253639676690432 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Daisy X Ji |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T16:54:05Z |
| format | Article |
| id | doaj.art-a13a048f3761473cb07137e4ffca8ea4 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:54:05Z |
| publishDate | 2021-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-a13a048f3761473cb07137e4ffca8ea42022-12-22T03:24:18ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.67290Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferonsDaisy X Ji0https://orcid.org/0000-0002-9148-3620Kristen C Witt1https://orcid.org/0000-0001-8744-9457Dmitri I Kotov2https://orcid.org/0000-0001-7843-1503Shally R Margolis3Alexander Louie4Victoria Chevée5Katherine J Chen6Moritz M Gaidt7Harmandeep S Dhaliwal8Angus Y Lee9Stephen L Nishimura10Dario S Zamboni11https://orcid.org/0000-0002-7856-7512Igor Kramnik12https://orcid.org/0000-0001-6511-9246Daniel A Portnoy13K Heran Darwin14Russell E Vance15https://orcid.org/0000-0002-6686-3912Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision 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 StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDivision 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 StatesDivision of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesCancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesCancer Research Laboratory, University of California, Berkeley, Berkeley, United StatesDepartment of Pathology, University of California, San Francisco, San Francisco, United StatesDepartment of Cell Biology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, BrazilThe National Emerging Infectious Diseases Laboratory, Department of Medicine (Pulmonary Center), and Department of Microbiology, Boston University School of Medicine, Boston, United StatesDivision 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 StatesDepartment of Microbiology, New York University Grossman School of Medicine, New York, United StatesDivision 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 StatesType 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.https://elifesciences.org/articles/67290mycobacterium tuberculosislegionella pneumophilatype i interferon |
| spellingShingle | 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 Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons eLife mycobacterium tuberculosis legionella pneumophila type i interferon |
| title | Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons |
| title_full | Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons |
| title_fullStr | Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons |
| title_full_unstemmed | Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons |
| title_short | Role of the transcriptional regulator SP140 in resistance to bacterial infections via repression of type I interferons |
| title_sort | role of the transcriptional regulator sp140 in resistance to bacterial infections via repression of type i interferons |
| topic | mycobacterium tuberculosis legionella pneumophila type i interferon |
| url | https://elifesciences.org/articles/67290 |
| work_keys_str_mv | AT daisyxji roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT kristencwitt roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT dmitriikotov roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT shallyrmargolis roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT alexanderlouie roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT victoriachevee roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT katherinejchen roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT moritzmgaidt roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT harmandeepsdhaliwal roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT angusylee roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT stephenlnishimura roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT darioszamboni roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT igorkramnik roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT danielaportnoy roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT kherandarwin roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons AT russellevance roleofthetranscriptionalregulatorsp140inresistancetobacterialinfectionsviarepressionoftypeiinterferons |