The interferon landscape along the respiratory tract impacts the severity of COVID-19

被引：174

作者：

Sposito, Benedetta ^{[1
,2
,3
]}

Broggi, Achille ^{[1
,17
]}

Pandolfi, Laura ^{[4
]}

Crotta, Stefania ^{[5
]}

Clementi, Nicola ^{[6
,7
]}

Ferrarese, Roberto ^{[6
]}

Sisti, Sofia ^{[6
]}

Criscuolo, Elena ^{[6
]}

Spreafico, Roberto ^{[8
]}

Long, Jaclyn M. ^{[1
]}

Ambrosi, Alessandro ^{[9
]}

Liu, Enju ^{[10
,11
]}

Frangipane, Vanessa ^{[4
]}

Saracino, Laura ^{[4
]}

Bozzini, Sara ^{[4
]}

Marongiu, Laura ^{[2
,3
]}

Facchini, Fabio A. ^{[2
,3
]}

Bottazzi, Andrea ^{[12
]}

Fossali, Tommaso ^{[13
]}

Colombo, Riccardo ^{[13
]}

Clementi, Massimo ^{[6
,7
]}

Tagliabue, Elena ^{[14
]}

Chou, Janet ^{[1
]}

Pontiroli, Antonio E. ^{[15
]}

Meloni, Federica ^{[4
,16
]}

Wack, Andreas ^{[5
]}

Mancini, Nicasio ^{[6
,7
]}

Zanoni, Ivan ^{[1
,10
]}

机构：

[1] Harvard Med Sch, Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA

[2] Univ Milano Bicocca, Dept Biotechnol & Biosci, I-20100 Milan, Italy

[3] Univ Milano Bicocca, PhD Program Mol & Translat Med DIMET, I-20100 Milan, Italy

[4] IRCCS San Matteo Hosp Fdn, Resp Dis Unit, I-27100 Pavia, Italy

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

[6] Univ Vita Salute San Raffaele, Lab Med Microbiol & Virol, I-20100 Milan, Italy

[7] IRCCS San Raffaele Hosp, I-20100 Milan, Italy

[8] Univ Calif Los Angeles, Inst Quantitat & Computat Biosci, Los Angeles, CA USA

[9] Univ Vita Salute San Raffaele, Fac Med & Surg, I-20100 Milan, Italy

[10] Harvard Med Sch, Boston Childrens Hosp, Div Gastroenterol, Boston, MA 02115 USA

[11] Boston Childrens Hosp, Inst Ctr Clin & Translat Res, Boston, MA 02115 USA

[12] IRCCS Policlin San Matteo Fdn, Dept Anesthesia & Crit Care Med, I-27100 Pavia, Italy

[13] Univ Milan, Luigi Sacco Hosp, ASST Fatebenefratelli Sacco, Div Anesthesiol & Intens Care, I-20100 Milan, Italy

[14] IRCCS Multimed, Value Based Healthcare Unit, I-20100 Milan, Italy

[15] Univ Milan, Dept Hlth Sci, I-20100 Milan, Italy

[16] Univ Pavia, Dept Internal Med & Pharmacol, I-27100 Pavia, Italy

[17] INSERM, U1104 Ctr Immunol Marseille Luminy CIML, F-13000 Marseille, France

来源：

CELL | 2021年 / 184卷 / 19期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

ACTIVATION;

D O I：

10.1016/j.cell.2021.08.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Severe coronavirus disease 2019 (COVID-19) is characterized by overproduction of immune mediators, but the role of interferons (IFNs) of the type I (IFN-I) or type III (IFN-III) families remains debated. We scrutinized the production of IFNs along the respiratory tract of COVID-19 patients and found that high levels of IFN-III, and to a lesser extent IFN-I, characterize the upper airways of patients with high viral burden but reduced disease risk or severity. Production of specific IFN-III, but not IFN-I, members denotes patients with a mild pathology and efficiently drives the transcription of genes that protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, compared to subjects with other infectious or noninfectious lung pathologies, IFNs are overrepresented in the lower airways of patients with severe COVID-19 that exhibit gene pathways associated with increased apoptosis and decreased proliferation. Our data demonstrate a dynamic production of IFNs in SARS-CoV-2-infected patients and show IFNs play opposing roles at distinct anatomical sites.

引用

页码：4953 / +

页数：32

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