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Autophagy regulates long-term cross-presentation by murine dendritic cells
- Source :
- European Journal of Immunology, European Journal of Immunology, 51(4), 835-847. WILEY, Eur J Immunology, European Journal of Immunology, 51, 4, pp. 835-847, European Journal of Immunology, 51, 835-847
- Publication Year :
- 2020
-
Abstract
- Autophagy has been reported to be involved in supporting antigen cross‐presentation by dendritic cells (DCs). We have shown that DCs have the ability to store antigen for a prolonged time in endolysosomal compartments and thereby sustain MHCI antigen cross‐presentation to CD8+ T cells. In the current study, we investigated the role of autophagy in long‐term antigen presentation. We show that the autophagy machinery has a negative impact on storage of antigen in DCs. Atg5–/–DCs which are deficient in autophagy or DCs treated with common autophagy inhibitors showed enhanced antigen storage and antigen cross‐presentation. This augmented antigen cross‐presentation effect is independent of altered proteasome enzyme activity or MHCI surface expression on DCs. We visualized that the storage compartments are in close proximity to LC3 positive autophagosomes. Our results indicate that autophagosomes disrupt antigen storage in DCs and thereby regulate long‐term MHCI cross‐presentation.<br />Protein antigen‐antibody complexes are efficiently taken up by dendritic cells and conserved in storage compartments for prolonged antigen cross‐presentation to CD8+ T cells. LC3‐positive autophagosomes can breakdown antigen storage compartments thereby regulating the cross‐presentation capacity of dendritic cells.
- Subjects :
- 0301 basic medicine
autophagy
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Antigen presentation
Immunology
Adaptive immunity
610 Medicine & health
Biology
CD8-Positive T-Lymphocytes
10263 Institute of Experimental Immunology
DC
Autophagy-Related Protein 5
Cell Line
03 medical and health sciences
0302 clinical medicine
Cross-Priming
Antigen
LC3
Immunology and Allergy
Animals
Basic
Mice, Knockout
2403 Immunology
Antigen Presentation
Microscopy, Confocal
Autophagy
Histocompatibility Antigens Class I
Autophagosomes
Cross-presentation
Dendritic Cells
Cell biology
Mice, Inbred C57BL
030104 developmental biology
Proteasome
cross‐presentation
2723 Immunology and Allergy
570 Life sciences
biology
Surface expression
Research Article|Basic
Wortmannin
MHCI
Nanomedicine Radboud Institute for Molecular Life Sciences [Radboudumc 19]
Microtubule-Associated Proteins
CD8
030215 immunology
Research Article
Subjects
Details
- ISSN :
- 15214141 and 00142980
- Volume :
- 51
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- European journal of immunology
- Accession number :
- edsair.doi.dedup.....24675a2a5c231057ff62bc8036640cd3