TLR2-mediated activation of innate responses in the upper airways confers antiviral protection of the lungs

被引：18

作者：

Deliyannis, Georgia ^{[1
]}

Wong, Chinn Yi ^{[1
]}

McQuilten, Hayley A. ^{[1
]}

Bachem, Annabell ^{[1
]}

Clarke, Michele ^{[1
]}

Jia, Xiaoxiao ^{[1
]}

Horrocks, Kylie ^{[1
]}

Zeng, Weiguang ^{[1
]}

Girkin, Jason ^{[2
,3
,4
]}

Scott, Nichollas E. ^{[1
]}

Londrigan, Sarah L. ^{[1
]}

Reading, Patrick C. ^{[1
,5
]}

Bartlett, Nathan W. ^{[2
,3
,4
]}

Kedzierska, Katherine ^{[1
]}

Brown, Lorena E. ^{[1
]}

Mercuri, Francesca ^{[6
]}

Demaison, Christophe ^{[6
]}

Jackson, David C. ^{[1
]}

Chua, Brendon Y. ^{[1
]}

机构：

[1] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, 792 Elizabeth St, Melbourne, Vic 3000, Australia

[2] Univ Newcastle, Fac Hlth & Med, Sch Biomed Sci & Pharm, Viral Immunol & Resp Dis Grp, Newcastle, NSW, Australia

[3] Univ Newcastle, Prior Res Ctr Hlth Lungs, Newcastle, NSW, Australia

[4] Hunter Med Res Inst, Newcastle, NSW, Australia

[5] WHO Collaborating Ctr Reference & Res Influenza, Peter Doherty Inst Infect & Immun, Melbourne, Vic, Australia

[6] Ena Resp, Melbourne, Vic, Australia

来源：

JCI INSIGHT | 2021年 / 6卷 / 05期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

INFLUENZA-VIRUS INFECTION; NITRIC-OXIDE SYNTHASE; EPITHELIAL-CELLS; IMMUNE-RESPONSE; A VIRUS; INTERFERON; TRANSMISSION; MACROPHAGES; RECOGNITION; INDUCTION;

D O I：

10.1172/jci.insight.140267

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The impact of respiratory virus infections on global health is felt not just during a pandemic, but endemic seasonal infections pose an equal and ongoing risk of severe disease. Moreover, vaccines and antiviral drugs are not always effective or available for many respiratory viruses. We investigated how induction of effective and appropriate antigen-independent innate immunity in the upper airways can prevent the spread of respiratory virus infection to the vulnerable lower airways. Activation of TLR2, when restricted to the nasal turbinates, resulted in prompt induction of innate immune-driven antiviral responses through action of cytokines, chemokines, and cellular activity in the upper but not the lower airways. We have defined how nasal epithelial cells and recruitment of macrophages work in concert and play pivotal roles to limit progression of influenza virus to the lungs and sustain protection for up to 7 days. These results reveal underlying mechanisms of how control of viral infection in the upper airways can occur and support the implementation of strategies that can activate TLR2 in nasal passages to provide rapid protection, especially for at-risk populations, against severe respiratory infection when vaccines and antiviral drugs are not always effective or available.

引用

页数：17