Stress signaling boosts interferon-induced gene transcription in macrophages

• DOI: 10.1126/scisignal.abq5389
• Publication Date: 2022-12-13T18:58:38Z
• Authors: Laura Boccuni; Elke Podgorschek; Moritz Schmiedeberg; Ekaterini Platanitis; Peter Traxler; Philipp Fischer; Alessia Schirripa; Philipp Novoszel; Angel R. Nebreda; J. Simon C. Arthur; Nikolaus Fortelny; Matthias Farlik; Veronika Sexl; Christoph Bock; Maria Sibilia; Pavel Kovarik; Mathias Müller; Thomas Decker
• Keywords: 0301 basic medicine; 570; Interferons/genetics; /dk/atira/pure/subjectarea/asjc/1300/1312; Transcription, Genetic; 610; p38 Mitogen-Activated Protein Kinases; name=Cell Biology; Interferon-gamma; 03 medical and health sciences; 106023 Molekularbiologie; Genetic; Macrophages/metabolism; Transcription Factors/metabolism; Phosphorylation; 106052 Cell biology; Interferon-gamma/metabolism; /dk/atira/pure/subjectarea/asjc/1300/1303; Macrophages; p38 Mitogen-Activated Protein Kinases/genetics; name=Biochemistry; name=Molecular Biology; 106023 Molecular biology; Interferons; 106052 Zellbiologie; /dk/atira/pure/subjectarea/asjc/1300/1307; Transcription; Signal Transduction; Transcription Factors

Promoters of antimicrobial genes function as logic boards, integrating signals innate immune responses. One such set is stimulated by interferon (IFN) signaling, and the expression these [IFN-stimulated (ISGs)] can be further modulated cell stress–induced pathways. Here, we investigated global effect stress-induced p38 mitogen-activated protein kinase (MAPK) signaling on response macrophages to IFN. In stress that coincided with IFN exposure, MAPK-activated transcription factors CREB c-Jun, in addition IFN-activated STAT family factors, bound ISGs. addition, MAPK induced activating histone modifications at loci ISGs nuclear translocation coactivator CRTC3. These actions synergistically enhanced ISG expression. Disrupting this synergy inhibitors improved viability infected Listeria monocytogenes . Our findings uncover a mechanism transcriptional synergism highlight biological consequences coincident IFN-stimulated signal transduction.