1. Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases.
- Author
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Singhania A, Graham CM, Gabryšová L, Moreira-Teixeira L, Stavropoulos E, Pitt JM, Chakravarty P, Warnatsch A, Branchett WJ, Conejero L, Lin JW, Davidson S, Wilson MS, Bancroft G, Langhorne J, Frickel E, Sesay AK, Priestnall SL, Herbert E, Ioannou M, Wang Q, Humphreys IR, Dodd J, Openshaw PJM, Mayer-Barber KD, Jankovic D, Sher A, Lloyd CM, Baldwin N, Chaussabel D, Papayannopoulos V, Wack A, Banchereau JF, Pascual VM, and O'Garra A
- Subjects
- Animals, Burkholderia pseudomallei, Candida albicans, Candidiasis immunology, Candidiasis microbiology, Gene Expression Regulation immunology, Influenza A Virus, H3N2 Subtype, Interferon Type I blood, Interferon Type I genetics, Interferon-gamma blood, Interferon-gamma genetics, Lung, Melioidosis immunology, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections genetics, Orthomyxoviridae Infections immunology, Orthomyxoviridae Infections virology, Receptor, Interferon alpha-beta, Receptors, Interferon, Respiratory Syncytial Virus Infections immunology, Interferon gamma Receptor, Candidiasis metabolism, Interferon Type I metabolism, Interferon-gamma metabolism, Melioidosis metabolism, Orthomyxoviridae Infections metabolism, Respiratory Syncytial Virus Infections metabolism
- 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.- Published
- 2019
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