Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases

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 and Anne O’Garra ()
Additional contact information
Akul Singhania: The Francis Crick Institute
Christine M. Graham: The Francis Crick Institute
Leona Gabryšová: The Francis Crick Institute
Lúcia Moreira-Teixeira: The Francis Crick Institute
Evangelos Stavropoulos: The Francis Crick Institute
Jonathan M. Pitt: The Francis Crick Institute
Probir Chakravarty: The Francis Crick Institute
Annika Warnatsch: The Francis Crick Institute
William J. Branchett: Imperial College London
Laura Conejero: London School of Hygiene and Tropical Medicine
Jing-Wen Lin: The Francis Crick Institute
Sophia Davidson: The Francis Crick Institute
Mark S. Wilson: The Francis Crick Institute
Gregory Bancroft: London School of Hygiene and Tropical Medicine
Jean Langhorne: The Francis Crick Institute
Eva Frickel: The Francis Crick Institute
Abdul K. Sesay: The Francis Crick Institute
Simon L. Priestnall: Royal Veterinary College
Eleanor Herbert: Royal Veterinary College
Marianna Ioannou: The Francis Crick Institute
Qian Wang: The Francis Crick Institute
Ian R. Humphreys: Cardiff University
Jonathan Dodd: Imperial College London
Peter J. M. Openshaw: Imperial College London
Katrin D. Mayer-Barber: National Institutes of Health
Dragana Jankovic: National Institutes of Health
Alan Sher: National Institutes of Health
Clare M. Lloyd: Imperial College London
Nicole Baldwin: Baylor Institute for Immunology Research
Damien Chaussabel: Sidra Medicine
Venizelos Papayannopoulos: The Francis Crick Institute
Andreas Wack: The Francis Crick Institute
Jacques F. Banchereau: The Jackson Laboratory for Genomic Medicine
Virginia M. Pascual: Weill Cornell Medical College
Anne O’Garra: The Francis Crick Institute

Nature Communications, 2019, vol. 10, issue 1, 1-21

Abstract: 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 during Toxoplasma gondii infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.

Date: 2019
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DOI: 10.1038/s41467-019-10601-6

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