Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation

• Published in: Cell reports (Cambridge) 2018-09, Vol.24 (13), p.3568-3581
• Main Authors: Weimershaus, Mirjana, Mauvais, François-Xavier, Saveanu, Loredana, Adiko, Cézaire, Babdor, Joël, Abramova, Anastasia, Montealegre, Sebastian, Lawand, Myriam, Evnouchidou, Irini, Huber, Katharina Julia, Chadt, Alexandra, Zwick, Markus, Vargas, Pablo, Dussiot, Michael, Lennon-Dumenil, Ana Maria, Brocker, Thomas, Al-Hasani, Hadi, van Endert, Peter
• Format: Article
• Language: English
• Subjects: Animals; antigen presentation; Cells, Cultured; Cellular Biology; cross-presentation; Cross-Priming; dendritic cell; endosome; Endosomes - metabolism; Female; Histocompatibility Antigens Class I - immunology; Immunity, Innate; kinesin; Kinesin - metabolism; Life Sciences; Male; MHC class I; Mice; Microtubules - metabolism; Phagosomes - immunology; Protein Transport; rab GTP-Binding Proteins - metabolism; Rab14; Receptors, Fc - metabolism; small GTPase; Subcellular Processes; Toll-Like Receptor 4 - metabolism
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2018.08.041

Both cross-presentation of antigens by dendritic cells, a key pathway triggering T cell immunity and immune tolerance, and survival of several pathogens residing in intracellular vacuoles are intimately linked to delayed maturation of vesicles containing internalized antigens and microbes. However, how early endosome or phagosome identity is maintained is incompletely understood. We show that Toll-like receptor 4 (TLR4) and Fc receptor ligation induces interaction of the GTPase Rab14 with the kinesin KIF16b mediating plus-end-directed microtubule transport of endosomes. As a result, Rab14 recruitment to phagosomes delays their maturation and killing of an internalized pathogen. Enhancing anterograde transport by overexpressing Rab14, promoting the GTP-bound Rab14 state, or inhibiting retrograde transport upregulates cross-presentation. Conversely, reducing Rab14 expression, destabilizing Rab14 endosomes, and inhibiting anterograde microtubule transport by Kif16b knockdown compromise cross-presentation. Therefore, regulation of early endosome trafficking by innate immune signals is a critical parameter in cross-presentation by dendritic cells. [Display omitted] •Innate immune signals induce formation of a complex of Rab14 with the kinesin KIF16B•This complex promotes anterograde microtubule transport of endosomes and phagosomes•Plus-end transport favors efficient cross-presentation of internalized antigens•Disruption of the complex accelerates phagosome maturation and microbial killing Weimershaus et al. identify a molecular complex that controls the intracellular trafficking along microtubules of antigens internalized by dendritic cells. They show that this trafficking is regulated by innate immune signals and regulates presentation of internalized antigens to T lymphocytes.