Intranasal introduction of Fc-fused interleukin-7 provides long-lasting prophylaxis against lethal influenza virus infection

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dc.contributor.authorM C Kang-
dc.contributor.authorD H Choi-
dc.contributor.authorY W Choi-
dc.contributor.authorS J Park-
dc.contributor.authorH Namkoong-
dc.contributor.authorK S Park-
dc.contributor.authorS S Ahn-
dc.contributor.authorC D Surh-
dc.contributor.authorSun Woo Yoon-
dc.contributor.authorDoo-Jin Kim-
dc.contributor.authorJ A Choi-
dc.contributor.authorY Park-
dc.contributor.authorY C Sung-
dc.contributor.authorS W Lee-
dc.date.accessioned2017-04-19T10:23:41Z-
dc.date.available2017-04-19T10:23:41Z-
dc.date.issued2016-
dc.identifier.issn0022538X-
dc.identifier.uri10.1128/JVI.02768-15ko
dc.identifier.urihttps://oak.kribb.re.kr/handle/201005/13317-
dc.description.abstractInfluenza A virus (IAV) infection frequently causes hospitalization and mortality due to severe immunopathology. Annual vaccination and antiviral drugs are the current countermeasures against IAV infection, but they have a limited efficacy against new IAV variants. Here, we show that intranasal pretreatment with Fc-fused interleukin-7 (IL-7-mFc) protects mice from lethal IAV infections. The protective activity of IL-7-mFc relies on transcytosis via neonatal Fc receptor (FcRn) in the lung and lasts for several weeks. Introduction of IL-7-mFc alters pulmonary immune environments, leading to recruitment of T cells from circulation and their subsequent residency as tissue-resident memory-like T (TRM-like) cells. IL-7-mFc-primed pulmonary TRM-like cells contribute to protection upon IAV infection by dual modes. First, TRM-like cells, although not antigen specific but polyclonal, attenuate viral replication at the early phase of IAV infection. Second, TRM-like cells augment expansion of IAV-specific cytotoxic T lymphocytes (CTLs), in particular at the late phase of infection, which directly control viruses. Thus, accelerated viral clearance facilitated by pulmonary T cells, which are either antigen specific or not, alleviates immunopathology in the lung and mortality from IAV infection. Depleting a subset of pulmonary T cells indicates that both CD4 and CD8 T cells contribute to protection from IAV, although IL-7-primed CD4 T cells have a more prominent role. Collectively, we propose intranasal IL-7-mFc pretreatment as an effective means for generating protective immunity against IAV infections, which could be applied to a potential prophylaxis for influenza pandemics in the future.-
dc.publisherAmer Soc Microb-
dc.titleIntranasal introduction of Fc-fused interleukin-7 provides long-lasting prophylaxis against lethal influenza virus infection-
dc.title.alternativeIntranasal introduction of Fc-fused interleukin-7 provides long-lasting prophylaxis against lethal influenza virus infection-
dc.typeArticle-
dc.citation.titleJournal of Virology-
dc.citation.number5-
dc.citation.endPage2284-
dc.citation.startPage2273-
dc.citation.volume90-
dc.contributor.affiliatedAuthorSun Woo Yoon-
dc.contributor.affiliatedAuthorDoo-Jin Kim-
dc.contributor.alternativeName강문철-
dc.contributor.alternativeName최동훈-
dc.contributor.alternativeName최영우-
dc.contributor.alternativeName박성정-
dc.contributor.alternativeName남궁홍-
dc.contributor.alternativeName박기석-
dc.contributor.alternativeName안소신-
dc.contributor.alternativeNameSurh-
dc.contributor.alternativeName윤선우-
dc.contributor.alternativeName김두진-
dc.contributor.alternativeName최정아-
dc.contributor.alternativeName박윤지-
dc.contributor.alternativeName성영철-
dc.contributor.alternativeName이승우-
dc.identifier.bibliographicCitationJournal of Virology, vol. 90, no. 5, pp. 2273-2284-
dc.identifier.doi10.1128/JVI.02768-15-
dc.description.journalClassY-
Appears in Collections:
Division of Research on National Challenges > Infectious Disease Research Center > 1. Journal Articles
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