Interferon-λ Mediates Non-redundant Front-Line Antiviral Protection against Influenza Virus Infection without Compromising Host Fitness

被引：367

作者：

Galani, Ioanna E. ^{[1
]}

Triantafyllia, Vasiliki ^{[1
]}

Eleminiadou, Evridiki-Evangelia ^{[1
]}

Koltsida, Ourania ^{[1
]}

Stavropoulos, Athanasios ^{[1
]}

Manioudaki, Maria ^{[1
]}

Thanos, Dimitris ^{[2
]}

Doyle, Sean E. ^{[3
]}

Kotenko, Sergei V. ^{[4
]}

Thanopoulou, Kalliopi ^{[1
]}

Andreakos, Evangelos ^{[1
]}

机构：

[1] Acad Athens, Biomed Res Fdn, Lab Immunobiol, Ctr Clin Expt Surg & Translat Res, Athens 11527, Greece

[2] Acad Athens, Biomed Res Fdn, Lab Mol Biol, Ctr Basic Res, Athens 11527, Greece

[3] ZymoGenetics Inc, Seattle, WA 98102 USA

[4] State Univ New Jersey, Dept Microbiol Biochem & Mol Genet, Ctr Immunity & Inflammat, Univ Hosp Canc Ctr,New Jersey Med Sch, Newark, NJ 07103 USA

来源：

IMMUNITY | 2017年 / 46卷 / 05期

关键词：

HEPATITIS-C VIRUS; III INTERFERONS; T-CELLS; IFN; IMMUNITY; EXPRESSION; INDUCTION; REVEALS; COMPLEX; IL-29;

D O I：

10.1016/j.immuni.2017.04.025

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Lambda interferons (IFN lambda s) or type III IFNs share homology, expression patterns, signaling cascades, and antiviral functions with type I IFNs. This has complicated the unwinding of their unique non-redundant roles. Through the systematic study of influenza virus infection in mice, we herein show that IFN lambda s are the first IFNs produced that act at the epithelial barrier to suppress initial viral spread without activating inflammation. If infection progresses, type I IFNs come into play to enhance viral resistance and induce pro-inflammatory responses essential for confronting infection but causing immunopathology. Central to this are neutrophils which respond to both cytokines to upregulate antimicrobial functions but exhibit pro-inflammatory activation only to type I IFNs. Accordingly, Ifnlr1(-/-) mice display enhanced type I IFN production, neutrophilia, lung injury, and lethality, while therapeutic administration of PEG-IFN lambda potently suppresses these effects. IFN lambda s therefore constitute the front line of antiviral defense in the lung without compromising host fitness.

引用

页码：875 / +

页数：22