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

Singhania, A; Graham, C M; Gabryšová, L; Moreira-Teixeira, L; Stavropoulos, E; Pitt, J M; Chakravarty, P; Warnatsch, A; Branchett, W J; Conejero, L; Lin, J-W; Davidson, S; Wilson, M S; Bancroft, G; Langhorne, J; Frickel, E; Sesay, A K; Priestnall, S L; Herbert, E; Ioannou, M; Wang, Q; Humphreys, I R; Dodd, J; Openshaw, P J M; Mayer-Barber, K D; Jankovic, D; Sher, A; Lloyd, C M; Baldwin, N; Chaussabel, D; Papayannopoulos, V; Wack, A; Banchereau, J F; Pascual, V M; O’Garra, A

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.

Citation

Singhania, A., Graham, C. M., Gabryšová, L., Moreira-Teixeira, L., Stavropoulos, E., Pitt, J. M., Chakravarty, P., Warnatsch, A., Branchett, W. J., Conejero, L., Lin, J.-W., Davidson, S., Wilson, M. S., Bancroft, G., Langhorne, J., Frickel, E., Sesay, A. K., Priestnall, S. L., Herbert, E., Ioannou, M., …O’Garra, A. (2019). Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases. Nature Communications, 10, https://doi.org/10.1038/s41467-019-10601-6

• Journal Article Type: Article
• Acceptance Date: May 9, 2019
• Publication Date: Jun 28, 2019
• Deposit Date: Aug 2, 2019
• Publicly Available Date: Aug 5, 2019
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Research
• Peer Reviewed: Peer Reviewed
• Volume: 10
• DOI: https://doi.org/10.1038/s41467-019-10601-6
• Public URL: https://rvc-repository.worktribe.com/output/1381476