PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection

Summary: PYHIN proteins AIM2 and IFI204 sense pathogen DNA, while other PYHINs have been shown to regulate host gene expression through as-yet unclear mechanisms. We characterize mouse PYHIN IFI207, which we find is not involved in DNA sensing but rather is required for cytokine promoter induction i...

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Main Authors: Marcin Baran, Claudia Feriotti, Aoife McGinley, Simon R. Carlile, Zhaozhao Jiang, Ricardo Calderon-Gonzalez, Amy Dumigan, Joana Sá-Pessoa, Caroline E. Sutton, Jay Kearney, Rachel M. McLoughlin, Kingston H.G. Mills, Katherine A. Fitzgerald, Jose A. Bengeochea, Andrew G. Bowie
Format: Article
Language:English
Published: Elsevier 2023-04-01
Series:Cell Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124723003522
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author Marcin Baran
Claudia Feriotti
Aoife McGinley
Simon R. Carlile
Zhaozhao Jiang
Ricardo Calderon-Gonzalez
Amy Dumigan
Joana Sá-Pessoa
Caroline E. Sutton
Jay Kearney
Rachel M. McLoughlin
Kingston H.G. Mills
Katherine A. Fitzgerald
Jose A. Bengeochea
Andrew G. Bowie
author_facet Marcin Baran
Claudia Feriotti
Aoife McGinley
Simon R. Carlile
Zhaozhao Jiang
Ricardo Calderon-Gonzalez
Amy Dumigan
Joana Sá-Pessoa
Caroline E. Sutton
Jay Kearney
Rachel M. McLoughlin
Kingston H.G. Mills
Katherine A. Fitzgerald
Jose A. Bengeochea
Andrew G. Bowie
author_sort Marcin Baran
collection DOAJ
description Summary: PYHIN proteins AIM2 and IFI204 sense pathogen DNA, while other PYHINs have been shown to regulate host gene expression through as-yet unclear mechanisms. We characterize mouse PYHIN IFI207, which we find is not involved in DNA sensing but rather is required for cytokine promoter induction in macrophages. IFI207 co-localizes with both active RNA polymerase II (RNA Pol II) and IRF7 in the nucleus and enhances IRF7-dependent gene promoter induction. Generation of Ifi207−/− mice shows no role for IFI207 in autoimmunity. Rather, IFI207 is required for the establishment of a Klebsiella pneumoniae lung infection and for Klebsiella macrophage phagocytosis. These insights into IFI207 function illustrate that PYHINs can have distinct roles in innate immunity independent of DNA sensing and highlight the need to better characterize the whole mouse locus, one gene at a time.
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spelling doaj.art-f56f8dac50b94ee2b449ad3b6f42ddc82023-04-06T06:10:51ZengElsevierCell Reports2211-12472023-04-01424112341PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infectionMarcin Baran0Claudia Feriotti1Aoife McGinley2Simon R. Carlile3Zhaozhao Jiang4Ricardo Calderon-Gonzalez5Amy Dumigan6Joana Sá-Pessoa7Caroline E. Sutton8Jay Kearney9Rachel M. McLoughlin10Kingston H.G. Mills11Katherine A. Fitzgerald12Jose A. Bengeochea13Andrew G. Bowie14School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, 97 Lisburn Road, Belfast, UKSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandDivision of Innate Immunity, University of Massachusetts Chan Medical School, Worcester, MA, USAWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, 97 Lisburn Road, Belfast, UKWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, 97 Lisburn Road, Belfast, UKWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, 97 Lisburn Road, Belfast, UKSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, IrelandDivision of Innate Immunity, University of Massachusetts Chan Medical School, Worcester, MA, USAWellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, 97 Lisburn Road, Belfast, UKSchool of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2 Dublin, Ireland; Corresponding authorSummary: PYHIN proteins AIM2 and IFI204 sense pathogen DNA, while other PYHINs have been shown to regulate host gene expression through as-yet unclear mechanisms. We characterize mouse PYHIN IFI207, which we find is not involved in DNA sensing but rather is required for cytokine promoter induction in macrophages. IFI207 co-localizes with both active RNA polymerase II (RNA Pol II) and IRF7 in the nucleus and enhances IRF7-dependent gene promoter induction. Generation of Ifi207−/− mice shows no role for IFI207 in autoimmunity. Rather, IFI207 is required for the establishment of a Klebsiella pneumoniae lung infection and for Klebsiella macrophage phagocytosis. These insights into IFI207 function illustrate that PYHINs can have distinct roles in innate immunity independent of DNA sensing and highlight the need to better characterize the whole mouse locus, one gene at a time.http://www.sciencedirect.com/science/article/pii/S2211124723003522CP: Immunology
spellingShingle Marcin Baran
Claudia Feriotti
Aoife McGinley
Simon R. Carlile
Zhaozhao Jiang
Ricardo Calderon-Gonzalez
Amy Dumigan
Joana Sá-Pessoa
Caroline E. Sutton
Jay Kearney
Rachel M. McLoughlin
Kingston H.G. Mills
Katherine A. Fitzgerald
Jose A. Bengeochea
Andrew G. Bowie
PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
Cell Reports
CP: Immunology
title PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
title_full PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
title_fullStr PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
title_full_unstemmed PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
title_short PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
title_sort pyhin protein ifi207 regulates cytokine transcription and irf7 and contributes to the establishment of k pneumoniae infection
topic CP: Immunology
url http://www.sciencedirect.com/science/article/pii/S2211124723003522
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