Delayed induction of type I and III interferons mediates nasal epithelial cell permissiveness to SARS-CoV-2

被引：77

作者：

Hatton, Catherine F. ^{[1
]}

Botting, Rachel A. ^{[2
]}

Duenas, Maria Emilia ^{[2
]}

Haq, Iram J. ^{[1
,3
]}

Verdon, Bernard ^{[2
]}

Thompson, Benjamin J. ^{[1
]}

Spegarova, Jarmila Stremenova ^{[1
]}

Gothe, Florian ^{[1
,4
]}

Stephenson, Emily ^{[2
]}

Gardner, Aaron I. ^{[1
]}

Murphy, Sandra ^{[2
]}

Scott, Jonathan ^{[1
]}

Garnett, James P. ^{[1
]}

Carrie, Sean ^{[5
]}

Powell, Jason ^{[1
]}

Khan, C. M. Anjam ^{[2
]}

Huang, Lei ^{[1
]}

Hussain, Rafiqul ^{[6
]}

Coxhead, Jonathan ^{[6
]}

Davey, Tracey ^{[7
]}

Simpson, A. John ^{[1
]}

Haniffa, Muzlifah ^{[2
,8
,9
,10
]}

Hambleton, Sophie ^{[1
,11
]}

Brodlie, Malcolm ^{[1
,3
]}

Ward, Chris ^{[1
]}

Trost, Matthias ^{[2
]}

Reynolds, Gary ^{[2
]}

Duncan, Christopher J. A. ^{[1
,12
]}

机构：

[1] Newcastle Univ, Translat & Clin Res Inst, Fac Med Sci, Newcastle Upon Tyne, Tyne & Wear, England

[2] Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England

[3] Newcastle Upon Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Paediat Resp Med, Newcastle Upon Tyne, Tyne & Wear, England

[4] Ludwig Maximilians Univ Munchen, Dept Pediat, Dr von Hauner Childrens Hosp, Univ Hosp, Munich, Germany

[5] Newcastle Univ, Populat Hlth Sci Inst, Newcastle Upon Tyne, Tyne & Wear, England

[6] Newcastle Univ, Biosci Inst, Genom Core Facil, Newcastle Upon Tyne, Tyne & Wear, England

[7] Newcastle Univ, Electron Microscopy Res Serv, Newcastle Upon Tyne, Tyne & Wear, England

[8] Newcastle Hosp NHS Fdn Trust, NIHR Newcastle Biomed Res Ctr, Newcastle Upon Tyne, Tyne & Wear, England

[9] Newcastle Hosp NHS Fdn Trust, Dept Dermatol, Newcastle Upon Tyne, Tyne & Wear, England

[10] Wellcome Sanger Inst, Wellcome Genome Campus, Cambridge, England

[11] Newcastle Upon Tyne Hosp NHS Fdn Trust, Great North Childrens Hosp, Newcastle Upon Tyne, Tyne & Wear, England

[12] Newcastle Upon Tyne Hosp NHS Fdn Trust, Dept Infect & Trop Med, Newcastle Upon Tyne, Tyne & Wear, England

来源：

NATURE COMMUNICATIONS | 2021年 / 12卷 / 01期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 英国医学研究理事会;

关键词：

INTRINSIC IMMUNITY; INFECTION;

D O I：

10.1038/s41467-021-27318-0

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：

The innate immune response in epithelial cells after SARS-CoV-2 infection is not fully understood. Here the authors use human air-liquid interface culture and show single cell transcription changes and delayed type I Interferon responses after SARS-CoV-2 infection compared with other respiratory viruses. The nasal epithelium is a plausible entry point for SARS-CoV-2, a site of pathogenesis and transmission, and may initiate the host response to SARS-CoV-2. Antiviral interferon (IFN) responses are critical to outcome of SARS-CoV-2. Yet little is known about the interaction between SARS-CoV-2 and innate immunity in this tissue. Here we apply single-cell RNA sequencing and proteomics to a primary cell model of human nasal epithelium differentiated at air-liquid interface. SARS-CoV-2 demonstrates widespread tropism for nasal epithelial cell types. The host response is dominated by type I and III IFNs and interferon-stimulated gene products. This response is notably delayed in onset relative to viral gene expression and compared to other respiratory viruses. Nevertheless, once established, the paracrine IFN response begins to impact on SARS-CoV-2 replication. When provided prior to infection, recombinant IFN beta or IFN lambda 1 induces an efficient antiviral state that potently restricts SARS-CoV-2 viral replication, preserving epithelial barrier integrity. These data imply that the IFN-I/III response to SARS-CoV-2 initiates in the nasal airway and suggest nasal delivery of recombinant IFNs to be a potential chemoprophylactic strategy.

引用

页数：17

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