期刊
IMMUNITY
卷 43, 期 6, 页码 1087-1100出版社
CELL PRESS
DOI: 10.1016/j.immuni.2015.11.006
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资金
- French National Research Agency through the Investments for the Future'' program (France-BioImaging) [ANR-10-INSB-04, ANR-11-LABX-0043]
- CelTisPhyBio Labex, IDEX PSL [ANR-10-LBX-0038, ANR-10-IDEX-0001-02 PSL]
- European Research Council [340046]
- La Ligue Nationale contre le Cancer [EL2014.LNCC/SA]
- Fonds Wetenschappelijk Onderzoek (FWO)
- Interuniversity Attraction Poles'' (IAP7)
- Ghent University Concerted Research Actions'' (GOA)
- Ghent University Group-ID MRP
- EMBO long-term fellowship [ALTF 883-2011]
- FWO [11W8415N, 1526615N]
- La Ligue contre le Cancer
- Fondation Recherche Medicale [SPF20101221176]
- omics@VIB program (Marie Curie FP7 People)
- European Research Council (ERC) [340046] Funding Source: European Research Council (ERC)
The initiation of cytotoxic immune responses by dendritic cells (DCs) requires the presentation of antigenic peptides derived from phagocytosed microbes and infected or dead cells to CD8(+) T cells, a process called cross-presentation. Antigen cross-presentation by non-activated DCs, however, is not sufficient for the effective induction of immune responses. Additionally, DCs need to be activated through innate receptors, like Toll-like receptors (TLRs). During DC maturation, cross-presentation efficiency is first upregulated and then turned off. Here we show that during this transient phase of enhanced cross-presentation, phago-lysosome fusion was blocked by the topological re-organization of lysosomes into perinuclear clusters. LPS-induced lysosomal clustering, inhibition of phago-lysosome fusion and enhanced cross-presentation, all required expression of the GTPase Rab34. We conclude that TLR4 engagement induces a Rab34-dependent re-organization of lysosomal distribution that delays antigen degradation to transiently enhance cross- presentation, thereby optimizing the priming of CD8(+) T cell responses against pathogens.
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