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

Baran, Marcin
Feriotti, Claudia
McGinley, Aoife
Carlile, Simon R
Jiang, Zhaozhao
Calderon-Gonzalez, Ricardo
Dumigan, Amy
Sá-Pessoa, Joana
Sutton, Caroline E
Kearney, Jay
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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.

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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. PYHIN protein IFI207 regulates cytokine transcription and IRF7 and contributes to the establishment of K. pneumoniae infection. Cell Rep. 2023 Apr 25;42(4):112341. doi: 10.1016/j.celrep.2023.112341. Epub 2023 Apr 4. PMID: 37018072.

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10.1016/j.celrep.2023.112341
PubMed ID
37018072
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Copyright 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Attribution-NonCommercial-NoDerivatives 4.0 International