tetano
Editor, Senior Moderator
Immunology. 2016 Jan 23. doi: 10.1111/imm.12587. [Epub ahead of print]
[h=1]Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection.[/h] Zang F[SUP]1[/SUP], Chen Y[SUP]2[/SUP], Lin Z[SUP]3[/SUP], Cai Z[SUP]4[/SUP], Yu L[SUP]4[/SUP], Xu F[SUP]5[/SUP], Wang J[SUP]6[/SUP], Zhu W[SUP]7[/SUP], Lu H[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+/-[/SUP] mice, we found that bone marrow-derived DCs from wild type mice (WT BMDCs) presented a more mature phenotype upon H1N1 infection. WT BMDCs secreted higher levels of IL-6, TNF-α, IFN-β, IL-12p70 and IFN-γ than did Beclin-1[SUP]+/-[/SUP] BMDCs. In contrast to Beclin-1[SUP]+/-[/SUP] BMDCs, H1N1-infected WT BMDCs exhibited increased activation of ERK, JNK, p38, and NF-κB as well as IRF7 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[SUP]+/-[/SUP] BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4[SUP]+[/SUP] T cell proliferation and driving Th1, Th2 and Th17 cell differentiation while inhibiting CD4[SUP]+[/SUP] Foxp3[SUP]+[/SUP] regulatory T cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the OVA antigen to CD8[SUP]+[/SUP] T cells. We consistently found that Beclin-1[SUP]+/-[/SUP] BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses, which produced lower levels of IL-6, TNF-α and IFN-β in vivo. Altogether, 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Autophagy; H1N1; Toll-like receptor; dendritic cells
PMID: 26800655 [PubMed - as supplied by publisher]
[h=1]Autophagy is involved in regulating the immune response of dendritic cells to influenza A (H1N1) pdm09 infection.[/h] Zang F[SUP]1[/SUP], Chen Y[SUP]2[/SUP], Lin Z[SUP]3[/SUP], Cai Z[SUP]4[/SUP], Yu L[SUP]4[/SUP], Xu F[SUP]5[/SUP], Wang J[SUP]6[/SUP], Zhu W[SUP]7[/SUP], Lu H[SUP]1[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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[SUP]+/-[/SUP] mice, we found that bone marrow-derived DCs from wild type mice (WT BMDCs) presented a more mature phenotype upon H1N1 infection. WT BMDCs secreted higher levels of IL-6, TNF-α, IFN-β, IL-12p70 and IFN-γ than did Beclin-1[SUP]+/-[/SUP] BMDCs. In contrast to Beclin-1[SUP]+/-[/SUP] BMDCs, H1N1-infected WT BMDCs exhibited increased activation of ERK, JNK, p38, and NF-κB as well as IRF7 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[SUP]+/-[/SUP] BMDCs, H1N1-infected WT BMDCs were more efficient in inducing allogeneic CD4[SUP]+[/SUP] T cell proliferation and driving Th1, Th2 and Th17 cell differentiation while inhibiting CD4[SUP]+[/SUP] Foxp3[SUP]+[/SUP] regulatory T cell differentiation. Moreover, WT BMDCs were more efficient at cross-presenting the OVA antigen to CD8[SUP]+[/SUP] T cells. We consistently found that Beclin-1[SUP]+/-[/SUP] BMDCs were inferior in their inhibition of H1N1 virus replication and their induction of H1N1-specific CD4[SUP]+[/SUP] and CD8[SUP]+[/SUP] T cell responses, which produced lower levels of IL-6, TNF-α and IFN-β in vivo. Altogether, 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. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
[h=4]KEYWORDS:[/h] Autophagy; H1N1; Toll-like receptor; dendritic cells
PMID: 26800655 [PubMed - as supplied by publisher]