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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-\u03b3 and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-\u03b3-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<jats:sup>+<\/jats:sup>effector cells. Type I IFN-inducible genes are abrogated in the absence of IFN-\u03b3 signaling and decrease in the absence of IFNAR signaling, both independently contributing to the regulation of granulocyte responses and pathology during<jats:italic>Toxoplasma gondii<\/jats:italic>infection. Our framework provides an ideal tool for comparative analyses of transcriptional signatures contributing to protection or pathogenesis in disease.<\/jats:p>","DOI":"10.1038\/s41467-019-10601-6","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T10:03:14Z","timestamp":1561716194000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":72,"title":["Transcriptional profiling unveils type I and II interferon networks in blood and tissues across diseases"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6941-3618","authenticated-orcid":false,"given":"Akul","family":"Singhania","sequence":"first","affiliation":[]},{"given":"Christine M.","family":"Graham","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3529-1306","authenticated-orcid":false,"given":"Leona","family":"Gabry\u0161ov\u00e1","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4817-8196","authenticated-orcid":false,"given":"L\u00facia","family":"Moreira-Teixeira","sequence":"additional","affiliation":[]},{"given":"Evangelos","family":"Stavropoulos","sequence":"additional","affiliation":[]},{"given":"Jonathan M.","family":"Pitt","sequence":"additional","affiliation":[]},{"given":"Probir","family":"Chakravarty","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2013-1625","authenticated-orcid":false,"given":"Annika","family":"Warnatsch","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4353-4857","authenticated-orcid":false,"given":"William J.","family":"Branchett","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6515-9221","authenticated-orcid":false,"given":"Laura","family":"Conejero","sequence":"additional","affiliation":[]},{"given":"Jing-Wen","family":"Lin","sequence":"additional","affiliation":[]},{"given":"Sophia","family":"Davidson","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1737-1281","authenticated-orcid":false,"given":"Mark S.","family":"Wilson","sequence":"additional","affiliation":[]},{"given":"Gregory","family":"Bancroft","sequence":"additional","affiliation":[]},{"given":"Jean","family":"Langhorne","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9515-3442","authenticated-orcid":false,"given":"Eva","family":"Frickel","sequence":"additional","affiliation":[]},{"given":"Abdul K.","family":"Sesay","sequence":"additional","affiliation":[]},{"given":"Simon L.","family":"Priestnall","sequence":"additional","affiliation":[]},{"given":"Eleanor","family":"Herbert","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1304-2667","authenticated-orcid":false,"given":"Marianna","family":"Ioannou","sequence":"additional","affiliation":[]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[]},{"given":"Ian R.","family":"Humphreys","sequence":"additional","affiliation":[]},{"given":"Jonathan","family":"Dodd","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7220-2555","authenticated-orcid":false,"given":"Peter J. 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