Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases
Year: 2019
Type: article
Abstract: Understanding how immune challenges elicit different responses is critical for diagnosing and deciphering immune regulation. Using a modular strategy to interpret the complex transcriptional host response in mouse models of infection and inflammation, we show a breadth of immune responses in the lung. Lung immune signatures are dominated by either IFN-γ and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-γ-inducible, but not IL-17- or allergy-associated signatures, are preserved in the blood. While IL-17-associated genes identified in lung are detected in blood, the allergy signature is only detectable in blood CD4+effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-γ signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology duringToxoplasma gondiiinfection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.
Source: Nature Communications
Authors: Akul Singhania, Christine M. Graham, Leona Gabryšová, Lúcia Moreira-Teixeira, Evangelos Stavropoulos, Jonathan M. Pitt, Probir Chakravarty, Annika Warnatsch, William J. Branchett, Laura Conejero, Jing-Wen Lin, Sophia Davidson, Mark S. Wilson, Gregory Bancroft, Jean Langhorne, Eva Frickel, Abdul K. Sesay, Simon L. Priestnall, Eleanor Herbert, Marianna Ioannou, Qian Wang, Ian R. Humphreys, Jonathan Dodd, Peter J. M. Openshaw, Katrin D. Mayer-Barber, Dragana Jankovic, Alan Sher, Clare M. Lloyd, Nicole Baldwin, Damien Chaussabel, Venizelos Papayannopoulos, Andreas Wack, Jacques F. Banchereau, Virginia M. Pascual, Anne O’Garra
Institutions: The Francis Crick Institute, Imperial College London, London School of Hygiene & Tropical Medicine, Royal Veterinary College, Cardiff University, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Sidra Medical and Research Center, The Jackson Laboratory for Genomic Medicine, Cornell University, Weill Cornell Medicine
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,200
Awards: G1123339746, G133569841, G1382785896, G1419362237, G143899097, G1804222254, G2276790277, G2506278645, G2513904301, G2874835306, G2944590941, G3341298347, G339059223, The role of innate immune regulation in viral pathogenesis and the development of anti-viral T cell memory, G3908721429, G4344689229, G4845263663, G5139134251, G5221904986, G5236897330, G5830407787, G5835771781, Epithelial-Alveolar Macrophage interactions underlying the regulation of allergic inflammation and remodelling ., G7209132623, Novel Approaches to Determine Molecular Mechanisms of Pathogenesis in Tuberculosis, The role of innate immune regulation in viral pathogenesis and the development of anti-viral T cell memory, G7847775018, G8103042128, G8279972828, G8403068438, G853588603, Regulation of antiviral inflammation through reactive oxygen species localisation, G8787058618, G8836123402, G8925602346, G8927371553
OpenAlex ID: W2954626553