Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation.
Cell Rep
; 24(13): 3568-3581, 2018 09 25.
Article
in En
| MEDLINE
| ID: mdl-30257216
ABSTRACT
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Endosomes
/
Histocompatibility Antigens Class I
/
Cross-Priming
/
Immunity, Innate
Limits:
Animals
Language:
En
Journal:
Cell Rep
Year:
2018
Document type:
Article
Affiliation country:
France