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

被引：49

作者：

Singhania, Akul ^{[1
]}

Graham, Christine M. ^{[1
,2
]}

Gabrysova, Leona ^{[1
,2
]}

Moreira-Teixeira, Lucia ^{[1
]}

Stavropoulos, Evangelos ^{[1
]}

Pitt, Jonathan M. ^{[1
]}

Chakravarty, Probir ^{[2
]}

Warnatsch, Annika ^{[3
]}

Branchett, William J. ^{[4
]}

Conejero, Laura ^{[5
]}

Lin, Jing-Wen ^{[6
]}

Davidson, Sophia ^{[7
]}

Wilson, Mark S. ^{[8
]}

Bancroft, Gregory ^{[5
]}

Langhorne, Jean ^{[6
]}

Frickel, Eva ^{[9
]}

Sesay, Abdul K. ^{[10
]}

Priestnall, Simon L. ^{[11
]}

Herbert, Eleanor ^{[11
]}

Ioannou, Marianna ^{[3
]}

Wang, Qian ^{[3
]}

Humphreys, Ian R. ^{[12
]}

Dodd, Jonathan ^{[13
]}

Openshaw, Peter J. M. ^{[13
]}

Mayer-Barber, Katrin D. ^{[14
]}

Jankovic, Dragana ^{[15
]}

Sher, Alan ^{[15
]}

Lloyd, Clare M. ^{[4
]}

Baldwin, Nicole ^{[16
]}

Chaussabel, Damien ^{[17
]}

Papayannopoulos, Venizelos ^{[3
]}

Wack, Andreas ^{[7
]}

Banchereau, Jacques F. ^{[18
]}

Pascual, Virginia M. ^{[19
]}

O'Garra, Anne ^{[1
,2
,20
]}

机构：

[1] Francis Crick Inst, Lab Immunoregulat & Infect, London NW1 1AT, England

[2] Francis Crick Inst, Bioinformat Core, London NW1 1AT, England

[3] Francis Crick Inst, Antimicrobial Def Lab, London NW1 1AT, England

[4] Imperial Coll London, Natl Heart & Lung Inst, Inflammat Repair & Dev Sect, London SW7 2AZ, England

[5] London Sch Hyg & Trop Med, London WC1E 7HT, England

[6] Francis Crick Inst, Malaria Lab, London NW1 1AT, England

[7] Francis Crick Inst, Immunoregulat Lab, London NW1 1AT, England

[8] Francis Crick Inst, Helminth Immunol Lab, London NW1 1AT, England

[9] Francis Crick Inst, Host Toxoplasma Interact Lab, London NW1 1AT, England

[10] Francis Crick Inst, Adv Sequencing Facil, London NW1 1AT, England

[11] Royal Vet Coll, Dept Pathobiol & Populat Sci, London AL9 7TA, England

[12] Cardiff Univ, Syst Immun Univ Res Inst, Div Infect & Immun, Cardiff CF14 4XN, S Glam, Wales

[13] Imperial Coll London, Natl Heart & Lung Inst, Resp Infect Sect, London W2 1PG, England

[14] NIAID, Inflammat & Innate Immun Unit, Lab Clin Immunol & Microbiol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[15] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[16] Baylor Inst Immunol Res, Dallas, TX 75204 USA

[17] Sidra Med, Syst Biol & Immunol Dept, POB 26999, Doha, Qatar

[18] Jackson Lab Genom Med, Farmington, CT 06030 USA

[19] Weill Cornell Med Coll, Drukier Inst Childrens Hlth, New York, NY 10065 USA

[20] Imperial Coll London, Natl Heart & Lung Inst, London W2 1PG, England

来源：

NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期

基金：

欧洲研究理事会; 英国医学研究理事会; 英国惠康基金;

关键词：

TOXOPLASMA-GONDII; IMMUNE-RESPONSE; IFN-GAMMA; LUNG INFLAMMATION; HOST-RESISTANCE; TUBERCULOSIS; MICE; NEUTROPHILS; INDUCTION; CELLS;

D O I：

10.1038/s41467-019-10601-6

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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-gamma and IFN-inducible, IL-17-induced neutrophil- or allergy-associated gene expression. Type I IFN and IFN-gamma-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-gamma 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.

引用

页数：21

共 87 条

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