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: Farong Zang, Yinghu Chen, Zhendong Lin, Zhijian Cai, Lei Yu, Feng Xu, Jiaoli Wang, Weiguo Zhu, Huoquan Lu
• Journal: Immunology (Immunology) Vol. 148 Issue 1 Pg. 56-69 (May 2016) ISSN: 1365-2567 [Electronic] England
• PMID: 26800655 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

• Apoptosis Regulatory Proteins
• Beclin-1
• Becn1 protein, mouse
• Cytokines
• Toll-Like Receptors

Topics

• Animals
• Antigen Presentation
• Apoptosis Regulatory Proteins (analysis)
• Autophagy
• Beclin-1
• Cytokines (biosynthesis)
• Dendritic Cells (immunology)
• Female
• Influenza A Virus, H1N1 Subtype (immunology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Orthomyxoviridae Infections (immunology)
• Signal Transduction
• Toll-Like Receptors (physiology)