Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection

作者：Zang, Farong; Chen, Yinghu; Lin, Zhendong; Cai, Zhijian; Yu, Lei; Xu, Feng; Wang, Jiaoli; Zhu, Weiguo^*; Lu, Huoquan^*

来源：Immunology, 2016, 148(1): 56-69.

DOI：10.1111/imm.12587

• autophagy
• dendritic cells
• H1N1
• toll-like receptor

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.

• 出版日期2016-5
• 单位浙江大学; 杭州市第一人民医院