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

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

doi:10.1016/j.celrep.2023.112341

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

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

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Abstract

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.

Original language	English
Article number	112341
Number of pages	26
Journal	Cell Reports
Volume	42
Issue number	4
DOIs	https://doi.org/10.1016/j.celrep.2023.112341
Publication status	Early online date - 04 Apr 2023

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PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection
© 2023 The Authors. This open access manuscript is distributed under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 5.07 MBLicence: CC BY-NC-ND

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Baran, M., Feriotti, C., McGinley, A., Carlile, S. R., Jiang, Z., Calderon-Gonzalez, R., Dumigan, A., Sá-Pessoa, J., Sutton, C. E., Kearney, J., McLoughlin, R. M., Mills, K. H. G., Fitzgerald, K. A., Bengeochea, J. A., & Bowie, A. G. (2023). PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection. Cell Reports, 42(4), Article 112341. Advance online publication. https://doi.org/10.1016/j.celrep.2023.112341

@article{ce84d15ef63946cb9993123254870560,

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

abstract = "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. ",

author = "Marcin Baran and Claudia Feriotti and Aoife McGinley and Carlile, {Simon R} and Zhaozhao Jiang and Ricardo Calderon-Gonzalez and Amy Dumigan and Joana S{\'a}-Pessoa and Sutton, {Caroline E} and Jay Kearney and McLoughlin, {Rachel M} and Mills, {Kingston H G} and Fitzgerald, {Katherine A} and Bengeochea, {Jose A} and Bowie, {Andrew G}",

year = "2023",

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doi = "10.1016/j.celrep.2023.112341",

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Baran, M, Feriotti, C, McGinley, A, Carlile, SR, Jiang, Z, Calderon-Gonzalez, R , Dumigan, A , Sá-Pessoa, J, Sutton, CE, Kearney, J, McLoughlin, RM, Mills, KHG, Fitzgerald, KA, Bengeochea, JA & Bowie, AG 2023, 'PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection', Cell Reports, vol. 42, no. 4, 112341. https://doi.org/10.1016/j.celrep.2023.112341

TY - JOUR

T1 - PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection

AU - Baran, Marcin

AU - Feriotti, Claudia

AU - McGinley, Aoife

AU - Carlile, Simon R

AU - Jiang, Zhaozhao

AU - Calderon-Gonzalez, Ricardo

AU - Dumigan, Amy

AU - Sá-Pessoa, Joana

AU - Sutton, Caroline E

AU - Kearney, Jay

AU - McLoughlin, Rachel M

AU - Mills, Kingston H G

AU - Fitzgerald, Katherine A

AU - Bengeochea, Jose A

AU - Bowie, Andrew G

PY - 2023/4/4

Y1 - 2023/4/4

N2 - 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.

AB - 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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DO - 10.1016/j.celrep.2023.112341

M3 - Article

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SN - 2211-1247

VL - 42

JO - Cell Reports

JF - Cell Reports

IS - 4

M1 - 112341

ER -

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

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