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PMID: 17663981 Published · ppublish English Comparative Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Innate and adaptive immunity through autophagy.

Immunity ·Vol. 27 ·No. 1 ·2007-07-00 ·Pages 11-21

Schmid D, Münz C

Abstract

The two main proteolytic machineries of eukaryotic cells, lysosomes and proteasomes, receive substrates by different routes. Polyubiquitination targets proteins for proteasomal degradation, whereas autophagy delivers intracellular material for lysosomal hydrolysis. The importance of autophagy for cell survival has long been appreciated, but more recently, its essential role in both innate and adaptive immunity has been characterized. Autophagy is now recognized to restrict viral infections and replication of intracellular bacteria and parasites. Additionally, this pathway delivers cytoplasmic antigens for MHC class II presentation to the adaptive immune system, which then in turn is able to regulate autophagy. At the same time, autophagy plays a role in the survival and the cell death of T cells. Thus, the immune system utilizes autophagic degradation of cytoplasmic material, to both restrict intracellular pathogens and regulate adaptive immunity.

MeSH Terms
Animals Autophagy/immunology Humans Immunity, Cellular Immunity, Innate
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Schmid Dorothee
Laboratory of Viral Immunobiology and Christopher H. Browne Center for Immunology and Immune Diseases, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.
Münz Christian
References (106)
106 references, click to expand
  1. Functional specificity of the mammalian Beclin-Vps34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking.
    J Cell Sci. 2006 Jan 15;119(Pt 2):259-70 PMID: 16390869
  2. Autophagy induction favours the generation and maturation of the Coxiella-replicative vacuoles.
    Cell Microbiol. 2005 Jul;7(7):981-93 PMID: 15953030
  3. Cytoplasmic processing is a prerequisite for presentation of an endogenous antigen by major histocompatibility complex class II proteins.
    J Exp Med. 2000 May 1;191(9):1513-24 PMID: 10790426
  4. A Salmonella protein causes macrophage cell death by inducing autophagy.
    J Cell Biol. 2003 Dec 8;163(5):1123-31 PMID: 14662750
  5. Subversion of cellular autophagosomal machinery by RNA viruses.
    PLoS Biol. 2005 May;3(5):e156 PMID: 15884975
  6. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death.
    J Biol Chem. 2005 May 27;280(21):20722-9 PMID: 15778222
  7. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy.
    Proc Natl Acad Sci U S A. 2007 Apr 3;104(14):6031-6 PMID: 17389386
  8. Antigen-specific memory B cell development.
    Annu Rev Immunol. 2005;23:487-513 PMID: 15771579
  9. Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1.
    J Exp Med. 2000 May 15;191(10):1649-60 PMID: 10811859
  10. Cytoplasmic bacteria can be targets for autophagy.
    Cell Microbiol. 2003 Jul;5(7):455-68 PMID: 12814436
  11. Open reading frame 1a-encoded subunits of the arterivirus replicase induce endoplasmic reticulum-derived double-membrane vesicles which carry the viral replication complex.
    J Virol. 1999 Mar;73(3):2016-26 PMID: 9971782
  12. Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death.
    J Immunol. 2006 Oct 15;177(8):5163-8 PMID: 17015701
  13. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein.
    J Virol. 1998 Nov;72(11):8586-96 PMID: 9765397
  14. Ubiquitin dependence of selective protein degradation demonstrated in the mammalian cell cycle mutant ts85.
    Cell. 1984 May;37(1):57-66 PMID: 6327060
  15. A statistical analysis of the relationship between degradative rates and molecular weights of proteins.
    Arch Biochem Biophys. 1975 Sep;170(1):213-9 PMID: 1164028
  16. Selective inactivation of a Fas-associated death domain protein (FADD)-dependent apoptosis and autophagy pathway in immortal epithelial cells.
    Mol Biol Cell. 2005 Mar;16(3):1189-99 PMID: 15635090
  17. Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape.
    Immunity. 2005 Feb;22(2):221-33 PMID: 15723810
  18. Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro-transcribed MUC1 RNA.
    Blood. 2005 Apr 15;105(8):3199-205 PMID: 15618468
  19. Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication.
    Proc Natl Acad Sci U S A. 2006 Sep 26;103(39):14578-83 PMID: 16983090
  20. Tolerogenic dendritic cells.
    Annu Rev Immunol. 2003;21:685-711 PMID: 12615891
  21. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes.
    J Clin Invest. 2006 Sep;116(9):2366-77 PMID: 16955139
  22. Interaction of Chlamydia trachomatis serovar L2 with the host autophagic pathway.
    Infect Immun. 2004 Aug;72(8):4751-62 PMID: 15271937
  23. A critical role for the autophagy gene Atg5 in T cell survival and proliferation.
    J Exp Med. 2007 Jan 22;204(1):25-31 PMID: 17190837
  24. Ultrastructural characterization of the delimiting membranes of isolated autophagosomes and amphisomes by freeze-fracture electron microscopy.
    Eur J Cell Biol. 2000 Dec;79(12):871-82 PMID: 11152279
  25. In vivo MHC class II presentation of cytosolic proteins revealed by rapid automated tandem mass spectrometry and functional analyses.
    Eur J Immunol. 2001 May;31(5):1485-94 PMID: 11465105
  26. Autophagy-dependent viral recognition by plasmacytoid dendritic cells.
    Science. 2007 Mar 9;315(5817):1398-401 PMID: 17272685
  27. Virulent Brucella abortus prevents lysosome fusion and is distributed within autophagosome-like compartments.
    Infect Immun. 1998 May;66(5):2387-92 PMID: 9573138
  28. A ubiquitin-like system mediates protein lipidation.
    Nature. 2000 Nov 23;408(6811):488-92 PMID: 11100732
  29. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1.
    Nat Genet. 2007 Feb;39(2):207-11 PMID: 17200669
  30. The UBA2 domain functions as an intrinsic stabilization signal that protects Rad23 from proteasomal degradation.
    Mol Cell. 2005 Apr 15;18(2):225-35 PMID: 15837425
  31. An intralysosomal hsp70 is required for a selective pathway of lysosomal protein degradation.
    J Cell Biol. 1997 May 19;137(4):825-34 PMID: 9151685
  32. Human IRGM induces autophagy to eliminate intracellular mycobacteria.
    Science. 2006 Sep 8;313(5792):1438-41 PMID: 16888103
  33. ELECTRON MICROSCOPIC STUDY OF THE FORMATION OF POLIOVIRUS.
    Virology. 1965 Jul;26:379-89 PMID: 14319710
  34. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles.
    J Exp Med. 1993 Jul 1;178(1):27-47 PMID: 8315383
  35. Viral subversion of the immune system.
    Annu Rev Immunol. 2000;18:861-926 PMID: 10837078
  36. Cytokine-induced, nitric oxide-dependent, intracellular antirickettsial activity of mouse endothelial cells.
    Lab Invest. 1997 Jan;76(1):129-38 PMID: 9010456
  37. Parasitophorous vacuoles of Leishmania mexicana acquire macromolecules from the host cell cytosol via two independent routes.
    J Cell Sci. 1999 Mar;112 ( Pt 5):681-93 PMID: 9973603
  38. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death.
    J Cell Biol. 2002 Apr 29;157(3):455-68 PMID: 11980920
  39. A protein conjugation system essential for autophagy.
    Nature. 1998 Sep 24;395(6700):395-8 PMID: 9759731
  40. Loss of autophagy in the central nervous system causes neurodegeneration in mice.
    Nature. 2006 Jun 15;441(7095):880-4 PMID: 16625205
  41. Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole.
    J Biol Chem. 2006 Apr 21;281(16):11374-83 PMID: 16495224
  42. Rotavirus NSP4 induces a novel vesicular compartment regulated by calcium and associated with viroplasms.
    J Virol. 2006 Jun;80(12):6061-71 PMID: 16731945
  43. Escape of intracellular Shigella from autophagy.
    Science. 2005 Feb 4;307(5710):727-31 PMID: 15576571
  44. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice.
    Nature. 2006 Jun 15;441(7095):885-9 PMID: 16625204
  45. Purification and characterization of autophagosomes from rat hepatocytes.
    Biochem J. 1998 Oct 15;335 ( Pt 2):217-24 PMID: 9761717
  46. Identification and characterization of severe acute respiratory syndrome coronavirus replicase proteins.
    J Virol. 2004 Sep;78(18):9977-86 PMID: 15331731
  47. Brucella evades macrophage killing via VirB-dependent sustained interactions with the endoplasmic reticulum.
    J Exp Med. 2003 Aug 18;198(4):545-56 PMID: 12925673
  48. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.
    Cell. 2004 Dec 17;119(6):753-66 PMID: 15607973
  49. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes.
    Immunity. 2007 Jan;26(1):79-92 PMID: 17182262
  50. Protective role of autophagy against Vibrio cholerae cytolysin, a pore-forming toxin from V. cholerae.
    Proc Natl Acad Sci U S A. 2007 Feb 6;104(6):1829-34 PMID: 17267617
  51. Cell biology of antigen processing in vitro and in vivo.
    Annu Rev Immunol. 2005;23:975-1028 PMID: 15771591
  52. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4.
    J Clin Invest. 2006 Aug;116(8):2161-72 PMID: 16886061
  53. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis.
    Nat Genet. 2007 May;39(5):596-604 PMID: 17435756
  54. Helping the CD8(+) T-cell response.
    Nat Rev Immunol. 2004 Aug;4(8):595-602 PMID: 15286726
  55. The autophagic and endocytic pathways converge at the nascent autophagic vacuoles.
    J Cell Biol. 1997 Jan 13;136(1):61-70 PMID: 9008703
  56. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.
    Cell. 2005 Sep 23;122(6):927-39 PMID: 16179260
  57. Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy.
    Eur J Immunol. 2003 May;33(5):1250-9 PMID: 12731050
  58. Macrophages rapidly transfer pathogens from lipid raft vacuoles to autophagosomes.
    Autophagy. 2005 Apr;1(1):53-8 PMID: 16874021
  59. CD8 T cell recognition of endogenously expressed epstein-barr virus nuclear antigen 1.
    J Exp Med. 2004 May 17;199(10):1409-20 PMID: 15148339
  60. SYFPEITHI: database for MHC ligands and peptide motifs.
    Immunogenetics. 1999 Nov;50(3-4):213-9 PMID: 10602881
  61. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is required for induction of autophagy during lumen formation in vitro.
    Proc Natl Acad Sci U S A. 2004 Mar 9;101(10):3438-43 PMID: 14993595
  62. Methods for monitoring autophagy.
    Int J Biochem Cell Biol. 2004 Dec;36(12):2491-502 PMID: 15325587
  63. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death.
    J Cell Biol. 2005 Nov 21;171(4):603-14 PMID: 16286508
  64. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein.
    Cell Host Microbe. 2007 Mar 15;1(1):23-35 PMID: 18005679
  65. Degradation of short- and long-lived proteins in perfused liver and in isolated autophagic vacuoles--lysosomes.
    Exp Mol Pathol. 1987 Feb;46(1):1-14 PMID: 3803535
  66. Virus-specific CD4+ T cells: ready for direct attack.
    J Exp Med. 2006 Apr 17;203(4):805-8 PMID: 16549599
  67. Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1.
    Proc Natl Acad Sci U S A. 1997 Nov 11;94(23):12616-21 PMID: 9356498
  68. Excessive degradation of intracellular protein in macrophages prevents presentation in the context of major histocompatibility complex class II molecules.
    Eur J Immunol. 1997 Jun;27(6):1506-14 PMID: 9209504
  69. Functions of lysosomes.
    Annu Rev Physiol. 1966;28:435-92 PMID: 5322983
  70. Endogenous MHC class II processing of a viral nuclear antigen after autophagy.
    Science. 2005 Jan 28;307(5709):593-6 PMID: 15591165
  71. Beclin-phosphatidylinositol 3-kinase complex functions at the trans-Golgi network.
    EMBO Rep. 2001 Apr;2(4):330-5 PMID: 11306555
  72. Glycine-alanine repeats impair proper substrate unfolding by the proteasome.
    EMBO J. 2006 Apr 19;25(8):1720-9 PMID: 16601692
  73. Regulation of starvation- and virus-induced autophagy by the eIF2alpha kinase signaling pathway.
    Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):190-5 PMID: 11756670
  74. Presentation of a cytosolic antigen by major histocompatibility complex class II molecules requires a long-lived form of the antigen.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14692-7 PMID: 8962116
  75. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker.
    Mol Biol Cell. 2004 Mar;15(3):1101-11 PMID: 14699058
  76. A receptor for the selective uptake and degradation of proteins by lysosomes.
    Science. 1996 Jul 26;273(5274):501-3 PMID: 8662539
  77. Survival of parvovirus B19-infected cells by cellular autophagy.
    Virology. 2006 Jun 5;349(2):254-63 PMID: 16643977
  78. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins.
    Science. 1989 Oct 20;246(4928):382-5 PMID: 2799391
  79. The bare lymphocyte syndrome and the regulation of MHC expression.
    Annu Rev Immunol. 2001;19:331-73 PMID: 11244040
  80. Unique properties of lamp2a compared to other lamp2 isoforms.
    J Cell Sci. 2000 Dec;113 Pt 24:4441-50 PMID: 11082038
  81. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes.
    Proc Natl Acad Sci U S A. 1982 Mar;79(6):1889-92 PMID: 6952238
  82. Autophagosome-associated variant isoforms of cytosolic enzymes.
    Biochem J. 2000 Dec 15;352 Pt 3:773-81 PMID: 11104685
  83. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity.
    Immunity. 2007 Jul;27(1):135-44 PMID: 17658277
  84. Uptake and degradation of glyceraldehyde-3-phosphate dehydrogenase by rat liver lysosomes.
    J Biol Chem. 1993 May 15;268(14):10463-70 PMID: 8486700
  85. Coronavirus replication complex formation utilizes components of cellular autophagy.
    J Biol Chem. 2004 Mar 12;279(11):10136-41 PMID: 14699140
  86. Positive and negative selection of T cells.
    Annu Rev Immunol. 2003;21:139-76 PMID: 12414722
  87. Autophagy: a forty-year search for a missing membrane source.
    PLoS Biol. 2006 Feb;4(2):e36 PMID: 16464128
  88. Inhibition of antigen processing by the internal repeat region of the Epstein-Barr virus nuclear antigen-1.
    Nature. 1995 Jun 22;375(6533):685-8 PMID: 7540727
  89. An endogenous processing pathway in vaccinia virus-infected cells for presentation of cytoplasmic antigens to class II-restricted T cells.
    J Exp Med. 1990 Sep 1;172(3):947-54 PMID: 2388037
  90. Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages.
    J Exp Med. 2006 Sep 4;203(9):2063-71 PMID: 16940170
  91. Lysosomes and autophagy in cell death control.
    Nat Rev Cancer. 2005 Nov;5(11):886-97 PMID: 16239905
  92. Autophagy defends cells against invading group A Streptococcus.
    Science. 2004 Nov 5;306(5698):1037-40 PMID: 15528445
  93. Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes.
    J Cell Sci. 2004 Aug 15;117(Pt 18):4239-51 PMID: 15292400
  94. Isolation and characterization of rat liver amphisomes. Evidence for fusion of autophagosomes with both early and late endosomes.
    J Biol Chem. 1998 Aug 21;273(34):21883-92 PMID: 9705327
  95. Autophagy is an immediate macrophage response to Legionella pneumophila.
    Cell Microbiol. 2005 Jun;7(6):765-78 PMID: 15888080
  96. Protein turnover via autophagy: implications for metabolism.
    Annu Rev Nutr. 2007;27:19-40 PMID: 17311494
  97. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing.
    EMBO J. 2000 Nov 1;19(21):5720-8 PMID: 11060023
  98. Molecular dissection of autophagy: two ubiquitin-like systems.
    Nat Rev Mol Cell Biol. 2001 Mar;2(3):211-6 PMID: 11265251
  99. Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens.
    Immunity. 2005 May;22(5):571-81 PMID: 15894275
  100. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins.
    Proc Natl Acad Sci U S A. 2005 May 31;102(22):7922-7 PMID: 15894616
  101. Insertion of a sequence encoding light chain 3 of microtubule-associated proteins 1A and 1B in a pestivirus genome: connection with virus cytopathogenicity and induction of lethal disease in cattle.
    J Virol. 1998 May;72(5):4139-48 PMID: 9557703
  102. Autophagy regulates programmed cell death during the plant innate immune response.
    Cell. 2005 May 20;121(4):567-577 PMID: 15907470
  103. Porphyromonas gingivalis traffics to autophagosomes in human coronary artery endothelial cells.
    Infect Immun. 2001 Sep;69(9):5698-708 PMID: 11500446
  104. Protein translocation across membranes.
    Biochim Biophys Acta. 2001 Jul 2;1513(1):1-24 PMID: 11427190
  105. NF-kappaB activation represses tumor necrosis factor-alpha-induced autophagy.
    J Biol Chem. 2006 Oct 13;281(41):30373-82 PMID: 16857678
  106. Targeting of EBNA1 for rapid intracellular degradation overrides the inhibitory effects of the Gly-Ala repeat domain and restores CD8+ T cell recognition.
    J Biol Chem. 2001 Sep 7;276(36):33353-60 PMID: 11435434
Article Info
Journal
Immunity
Abbr.
Immunity
ISSN
1074-7613
DOI
10.1016/j.immuni.2007.07.004
Published
2007-07-00
Pages
11-21
Language
English
Region
United States
NLM ID
9432918
PMCID
PMC7118777
Subset
IM
Grants
NCI NIH HHS · R01 CA101741 · United States
NCI NIH HHS · R01 CA108609 · United States
NCI NIH HHS · R01CA108609 · United States
NCI NIH HHS · R01CA101741 · United States
External Links
PubMed source DOI: 10.1016/j.immuni.2007.07.004 PMC Full Text View journal details
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