Increased translocation of antigens to endosomes and TLR4 mediated endosomal recruitment of TAP contribute to nicotine augmented cross-presentation

// Yan Yan Wang 1 , Chun Fang Hu 1 , Juan Li 1 , Xiang You 1 , Feng Guang Gao 1, 2 1 Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen, People’s Republic of China 2 State Key Laboratory of Oncogenes and Related Genes, Shang Hai Jiao Tong University, Shanghai, People’s Republic of China Correspondence to: Feng Guang Gao, e-mail: gfengguang@xmu.edu.cn Keywords: mannose receptor, cross-presentation, α7 nicotinic acetylcholine receptor, dendritic cells, Toll-like receptor 4 Received: March 03, 2016     Accepted: May 02, 2016     Published: May 20, 2016 ABSTRACT Cross-presentation by dendritic cells (DCs) requires surface molecules such as lectin, CD40, langerin, heat shock protein, mannose receptor, mediated endocytosis, the endosomal translocation of internalized antigen, and the relocation of transporter associated with antigen processing (TAP). Although the activation of α7 nicotinic acetylcholine receptor (α7 nAchR) up-regulate surface molecule expression, augment endocytosis, and enhance cross-presentation, the molecular mechanism of α7 nAchR activation-increased cross-presentation is still poorly understood. In this study, we investigated the role of mannose receptor in nicotine-increased cross-presentation and the mechanism that endotoxins orchestrating the recruitment of TAP toward endosomes. We demonstrated that nicotine increase the expressiones of mannose receptor and Toll-like receptor 4 (TLR4) via PI3K-Akt-mTOR-p70S6 pathway. Both endosomal translocation of mannose receptor-internalized antigens and TLR4 sig- naling are necessary for nicotine-augmented cross-presentation and cross-priming. Importantly, the recruitment of TAP toward endosomes via TLR4-MyD88-IRAK4 signaling contributes to nicotine-increased cross-presentation and cross-activation of T cells. Thus, these data suggest that increased recruitment of TAP to Ag-containing vesicles contributes to the superior cross-presentation efficacy of α7 nAchR activated DCs.