Trif/Myd88-Dependent the Formation of Akt+Ikkα/Β+ Signalosome on Rab5+ Endosomes Contributes to the Cross-Presentation of Antigen Activated Dendritic Cell

Cross-presentation by dendritic cell (DC) requires the endosomal relocations of internalized exogenous antigens and endoplasmic reticulum protein Sec61. In despite that the treatment with antigens activates Akt and NF-κB pathways, the exact roles of Akt phosphorylation and NF-κB activation in cross-presentation are still poorly understood. In this study, we investigate the roles of Akt phosphorylation, IKKα/β activation and the mechanism that the antigens orchestrating the recruitment of Sec61 toward endosomes in cross-presentation. We demonstrate that the treatment with exogenous antigens increases the formation of Akt+IKKα/β+ signalosome on Rab5+ endosomes and augments the endosomal recruitment of Sec61 in the process of DC cross-presentation. Interestingly, TRIF/MyD88-dependent the formation of Akt+IKKα/β+ signalosomes mediates the relocation of Sec61 toward endosomes. Importantly, the MyD88-IRAK4 signaling contributes to exogenous ovalbumin-derived cross-presentation by recruiting Akt+IKKα/β+ signalosomes toward endosomes. Thus, these data suggest that TRIF/MyD88-dependent the formation of Akt+IKKα/β+ signalosome on Rab5+ endosomes contributes to the endosomal recruitment of Sec61 and the superior cross-presentation efficacy of antigen activated DC.