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

Singhania, A and Graham, C M and Gabryšová, L and Moreira-Teixeira, L and Stavropoulos, E and Pitt, J M and Chakravarty, P and Warnatsch, A and Branchett, W J and Conejero, L and Lin, J-W and Davidson, S and Wilson, M S and Bancroft, G and Langhorne, J and Frickel, E and Sesay, A K and Priestnall, S L and Herbert, E and Ioannou, M and Wang, Q and Humphreys, I R and Dodd, J and Openshaw, P J M and Mayer-Barber, K D and Jankovic, D and Sher, A and Lloyd, C M and Baldwin, N and Chaussabel, D and Papayannopoulos, V and Wack, A and Banchereau, J F and Pascual, V M and O’Garra, A (2019) Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases. Nature Communications, 10.

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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.