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Toll-like receptor 4 engagement on dendritic cells restrains phago-lysosome fusion and promotes cross-presentation of antigens

(2015) IMMUNITY. 43(6). p.1087-1100
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Abstract
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.
Keywords
PH, CROSSPRESENTATION, MATURATION, ACTIVATION, PRESENTING CELLS, PHAGOCYTOSIS, COMPARTMENT, CAPTURE, LIGANDS, RAB34

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Citation

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MLA
Alloatti, Andrés, et al. “Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens.” IMMUNITY, vol. 43, no. 6, 2015, pp. 1087–100.
APA
Alloatti, A., Kotsias, F., Pauwels, A.-M., Carpier, J.-M., Jouve, M., Timmerman, E., … Amigorena, S. (2015). Toll-like receptor 4 engagement on dendritic cells restrains phago-lysosome fusion and promotes cross-presentation of antigens. IMMUNITY, 43(6), 1087–1100.
Chicago author-date
Alloatti, Andrés, Fiorlla Kotsias, Anne-Marie Pauwels, Jean-Marie Carpier, Mabel Jouve, Evy Timmerman, Luigia Pace, et al. 2015. “Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens.” IMMUNITY 43 (6): 1087–1100.
Chicago author-date (all authors)
Alloatti, Andrés, Fiorlla Kotsias, Anne-Marie Pauwels, Jean-Marie Carpier, Mabel Jouve, Evy Timmerman, Luigia Pace, Pablo Vargas, Mathieu Maurin, Ulf Gehrmann, Leonel Joannas, Omar I Vivar, Ana-Maria Lennon-Duménil, Ariel Savina, Kris Gevaert, Rudi Beyaert, Eik Hoffmann, and Sebastian Amigorena. 2015. “Toll-like Receptor 4 Engagement on Dendritic Cells Restrains Phago-Lysosome Fusion and Promotes Cross-Presentation of Antigens.” IMMUNITY 43 (6): 1087–1100.
Vancouver
1.
Alloatti A, Kotsias F, Pauwels A-M, Carpier J-M, Jouve M, Timmerman E, et al. Toll-like receptor 4 engagement on dendritic cells restrains phago-lysosome fusion and promotes cross-presentation of antigens. IMMUNITY. 2015;43(6):1087–100.
IEEE
[1]
A. Alloatti et al., “Toll-like receptor 4 engagement on dendritic cells restrains phago-lysosome fusion and promotes cross-presentation of antigens,” IMMUNITY, vol. 43, no. 6, pp. 1087–1100, 2015.
@article{7039174,
  abstract     = {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.},
  author       = {Alloatti, Andrés and Kotsias, Fiorlla and Pauwels, Anne-Marie and Carpier, Jean-Marie and Jouve, Mabel and Timmerman, Evy and Pace, Luigia and Vargas, Pablo and Maurin, Mathieu and Gehrmann, Ulf and Joannas, Leonel and Vivar, Omar I and Lennon-Duménil, Ana-Maria and Savina, Ariel and Gevaert, Kris and Beyaert, Rudi and Hoffmann, Eik and Amigorena, Sebastian},
  issn         = {1074-7613},
  journal      = {IMMUNITY},
  keywords     = {PH,CROSSPRESENTATION,MATURATION,ACTIVATION,PRESENTING CELLS,PHAGOCYTOSIS,COMPARTMENT,CAPTURE,LIGANDS,RAB34},
  language     = {eng},
  number       = {6},
  pages        = {1087--1100},
  title        = {Toll-like receptor 4 engagement on dendritic cells restrains phago-lysosome fusion and promotes cross-presentation of antigens},
  url          = {http://dx.doi.org/10.1016/j.immuni.2015.11.006},
  volume       = {43},
  year         = {2015},
}

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