Abstract
Autophagy is a homeostatic process that enables eukaryotic cells to deliver cytoplasmic constituents for lysosomal degradation, to recycle nutrients and to survive during starvation. In addition to these primordial functions, autophagy has emerged as a key mechanism in orchestrating innate and adaptive immune responses to intracellular pathogens. Autophagy restricts viral infections as well as replication of intracellular bacteria and parasites and delivers pathogenic determinants for TLR stimulation and for MHC class II presentation to the adaptive immune system. Apart from its role in defense against pathogens, autophagy-mediated presentation of self-antigens in the steady state could have a crucial role in the induction and maintenance of CD4+ T-cell tolerance. This review describes the mechanisms by which the immune system utilizes autophagic degradation of cytoplasmic material to regulate adaptive immune responses.
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Abbreviations
- CMA:
-
chaperone-mediated autophagy
- Atg:
-
autophagy-related gene
- TLR:
-
Toll-like receptor
- TNF:
-
tumor necrosis factor
- MHC:
-
major histocompatibility complex
- DRiPs:
-
defective ribosomal products
- TAP:
-
transporter associated with antigen processing
- Ii:
-
invariant chain
- CLIP:
-
class II-associated Ii peptide
- APC:
-
antigen-presenting cell
- MIIC:
-
MHC class II containing compartment
- HLA:
-
human leukocyte antigen
- DC:
-
dendritic cell
- EBV:
-
Epstein–Barr virus
- LAMP:
-
lysosome-associated membrane protein
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Acknowledgements
JDL is a recipient of the Dana Foundation and Irvington Institute's Human Immunology Fellowship from the Cancer Research Institute and is supported by a Pilot Grant from the National Multiple Sclerosis Society (PP1145) and an Institutional Clinical and Translational Science Pilot and Collaborative Project Grant (to the Rockefeller University Hospital). CM is supported by the Dana Foundation's Neuroimmunology program, the Arnold and Mabel Beckman Foundation, the Alexandrine and Alexander Sinsheimer Foundation, the Burroughs Wellcome Fund, the Starr Foundation, the National Cancer Institute (R01CA108609 and R01CA101741), the National Institute of Allergy and Infectious Diseases (RFP-NIH-NIAID-DAIDS-BAA-06-19), the Foundation for the National Institutes of Health (Grand Challenges in Global Health), and an Institutional Clinical and Translational Science Award (to the Rockefeller University Hospital).
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Lünemann, J., Münz, C. Autophagy in CD4+ T-cell immunity and tolerance. Cell Death Differ 16, 79–86 (2009). https://doi.org/10.1038/cdd.2008.113
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