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Intranasal Introduction of Fc-Fused Interleukin-7 Provides Long-Lasting Prophylaxis against Lethal Influenza Virus Infection.
Kang, Moon Cheol; Choi, Dong-Hoon; Choi, Young Woo; Park, Seong Jeong; Namkoong, Hong; Park, Ki Seok; Ahn, So-Shin; Surh, Charles D; Yoon, Sun-Woo; Kim, Doo-Jin; Choi, Jung-ah; Park, Yunji; Sung, Young Chul; Lee, Seung-Woo.
Afiliação
  • Kang MC; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Choi DH; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Choi YW; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Park SJ; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Namkoong H; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Park KS; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Ahn SS; Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Surh CD; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Yoon SW; Viral Infectious Disease Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
  • Kim DJ; Viral Infectious Disease Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
  • Choi JA; Molecular Vaccinology Section, Laboratory Science Division, International Vaccine Institute, Seoul, Republic of Korea.
  • Park Y; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea.
  • Sung YC; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea ycsung@postech.ac.kr sw_lee@postech.ac.kr.
  • Lee SW; Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea Department of Life Sciences, Pohang University of Science and Technology, Pohang, Gyeongbuk, Republic of Korea ycsung@postech.ac.kr sw_lee@postech.ac.kr.
J Virol ; 90(5): 2273-84, 2015 Dec 09.
Article em En | MEDLINE | ID: mdl-26656713
ABSTRACT
UNLABELLED Influenza 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. IMPORTANCE The major consequence of a highly pathogenic IAV infection is severe pulmonary inflammation, which can result in organ failure and death at worst. Although vaccines for seasonal IAVs are effective, frequent variation of surface viral proteins hampers development of protective immunity. In this study, we demonstrated that intranasal IL-7-mFc pretreatment protected immunologically naive mice from lethal IAV infections. Intranasal pretreatment with IL-7-mFc induced an infiltration of T cells in the lung, which reside as effector/memory T cells with lung-retentive markers. Those IL-7-primed pulmonary T cells contributed to development of protective immunity upon IAV infection, reducing pulmonary immunopathology while increasing IAV-specific cytotoxic T lymphocytes. Since a single treatment with IL-7-mFc was effective in the protection against multiple strains of IAV for an extended period of time, our findings suggest a possibility that IL-7-mFc treatment, as a potential prophylaxis, can be developed for controlling highly pathogenic IAV infections.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Influenza A / Fragmentos Fc das Imunoglobulinas / Interleucina-7 / Infecções por Orthomyxoviridae / Fatores Imunológicos / Pulmão Limite: Animals Idioma: En Revista: J Virol Ano de publicação: 2015 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Vírus da Influenza A / Fragmentos Fc das Imunoglobulinas / Interleucina-7 / Infecções por Orthomyxoviridae / Fatores Imunológicos / Pulmão Limite: Animals Idioma: En Revista: J Virol Ano de publicação: 2015 Tipo de documento: Article