期刊
IMMUNOLOGY
卷 148, 期 1, 页码 56-69出版社
WILEY
DOI: 10.1111/imm.12587
关键词
autophagy; dendritic cells; H1N1; toll-like receptor
类别
资金
- Public Welfare Technology Application Research Project of Zhejiang Province [2013C33146]
- National Natural Science Foundation of China [81200014, 81300203]
- Major Science and Technology Special Project of Zhejiang Province [2014C13G2010065]
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. Wildtype BMDCs secreted higher levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), interferon-beta (IFN-beta), IL-12p70 and IFN-gamma 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-kappa B 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-alpha and IFN-beta in H1N1-infected BMDCs. In contrast to Beclin1(+/-) 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-alpha and IFN-beta 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.
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