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PMID: 24747745 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Essential role for autophagy in the maintenance of immunological memory against influenza infection.

Nature medicine ·Vol. 20 ·No. 5 ·2014-05-00 ·Pages 503-10

Chen M, Hong MJ, Sun H, Wang L, Shi X, Gilbert BE, Corry DB, Kheradmand F, Wang J

Abstract

Vaccination has been the most widely used strategy to protect against viral infections for centuries. However, the molecular mechanisms governing the long-term persistence of immunological memory in response to vaccines remain unclear. Here we show that autophagy has a critical role in the maintenance of memory B cells that protect against influenza virus infection. Memory B cells displayed elevated levels of basal autophagy with increased expression of genes that regulate autophagy initiation or autophagosome maturation. Mice with B cell-specific deletion of Atg7 (B/Atg7(-/-) mice) showed normal primary antibody responses after immunization against influenza but failed to generate protective secondary antibody responses when challenged with influenza viruses, resulting in high viral loads, widespread lung destruction and increased fatality. Our results suggest that autophagy is essential for the survival of virus-specific memory B cells in mice and the maintenance of protective antibody responses required to combat infections.

MeSH Terms
Animals Antibodies, Viral/biosynthesis,immunology Autophagy/immunology B-Lymphocytes/immunology Humans Immunization Immunologic Memory Influenza A Virus, H1N1 Subtype/immunology Influenza Vaccines/therapeutic use Influenza, Human/immunology Mice
Chemicals
Antibodies, Viral Influenza Vaccines
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chen Min
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Hong Monica Jeongsoo
Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Sun Huanhuan
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Wang Lei
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Shi Xiurong
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
Gilbert Brian E
Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.
Corry David B
1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. [3] Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas, USA. [4] Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Kheradmand Farrah
1] Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Medicine, Baylor College of Medicine, Houston, Texas, USA. [3] Biology of Inflammation Center, Baylor College of Medicine, Houston, Texas, USA. [4] Center for Translational Research on Inflammatory Diseases, Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas, USA.
Wang Jin
Department of Pathology and Immunology, Baylor College of Medicine, Houston, Texas, USA.
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Article Info
Journal
Nature medicine
Abbr.
Nat Med
ISSN
1546-170X
DOI
10.1038/nm.3521
Published
2014-05-00
Epub
2014-00-20
Pages
503-10
Language
English
Region
United States
NLM ID
9502015
PMCID
PMC4066663
Subset
IM
Grants
CSRD VA · I01 CX000104 · United States
BLRD VA · I01 BX002221 · United States
NHLBI NIH HHS · R01HL117181 · United States
NHLBI NIH HHS · R01 HL117181 · United States
NIDDK NIH HHS · R01DK083164 · United States
External Links
PubMed source DOI: 10.1038/nm.3521 PMC Full Text View journal details
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