title: Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection.
abstract: Autophagy can mediate antiviral immunity. However, it remains unknown whether autophagy regulates the immune response of dendritic cells (DCs) to influenza A (H1N1) pdm09 infection. In this study, we found that infection with the H1N1 virus induced DC autophagy in an endocytosis-dependent manner. Compared with autophagy-deficient Beclin-1(+/-) mice, we found that bone-marrow-derived DCs from wild-type mice (WT BMDCs) presented a more mature phenotype on H1N1 infection. Wild-type BMDCs secreted higher levels of interleukin-6 (IL-6), tumour necrosis factor- α (TNF-α), interferon-β (IFN-β), IL-12p70 and IFN-γ than did Beclin-1(+/-) BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs exhibited increased activation of extracellular signal-regulated kinase, Jun N-terminal kinase, p38, and nuclear factor-κB as well as IFN regulatory factor 7 nuclear translocation. Blockade of autophagosomal and lysosomal fusion by bafilomycin A1 decreased the co-localization of H1N1 viruses, autophagosomes and lysosomes as well as the secretion of IL-6, TNF-α and IFN-β in H1N1-infected BMDCs. In contrast to Beclin-1(+/-) BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4(+) T-cell proliferation and driving T helper type 1, 2 and 17 cell differentiation while inhibiting CD4(+) Foxp3(+) regulatory T-cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the ovalbumin antigen to CD8(+) T cells. We consistently found that Beclin-1(+/-) BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4(+) and CD8(+) T-cell responses, which produced lower levels of IL-6, TNF-α and IFN-β in vivo. Our data indicate that autophagy is important in the regulation of the DC immune response to H1N1 infection, thereby extending our understanding of host immune responses to the virus.
authors.affiliation: Department of Respiration, The People's Hospital of Changxing County, Huzhou, China.
authors.forename: Farong
authors.initials: F
authors.lastname: Zang
authors.affiliation: Division of Infection Disease, Zhejiang Key Laboratory for Neonatal Diseases, Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Yinghu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Departments of Orthopedics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Infectious Diseases, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Respiratory Medicine, Affiliated Hangzhou Hospital (Hangzhou First People's Hospital), Nanjing Medical University, Hangzhou, China.
authors.forename: Jiaoli
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Cardiology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: Weiguo
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Respiration, The People's Hospital of Changxing County, Huzhou, China.
authors.forename: Huoquan
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D051017:Apoptosis Regulatory Proteins / Q000032:analysis; D001343:Autophagy; D000071186:Beclin-1; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D016207:Cytokines; D051193:Toll-Like Receptors
keywords: H1N1; autophagy; dendritic cells; toll-like receptor