Home LiteratureArticle Details
PMID: 25654553 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

Immunologic manifestations of autophagy.

The Journal of clinical investigation ·Vol. 125 ·No. 1 ·2015-01-00 ·Pages 75-84

Deretic V, Kimura T, Timmins G, Moseley P, Chauhan S, Mandell M

Abstract

The broad immunologic roles of autophagy span innate and adaptive immunity and are often manifested in inflammatory diseases. The immune effects of autophagy partially overlap with its roles in metabolism and cytoplasmic quality control but typically expand further afield to encompass unique immunologic adaptations. One of the best-appreciated manifestations of autophagy is protection against microbial invasion, but this is by no means limited to direct elimination of intracellular pathogens and includes a stratified array of nearly all principal immunologic processes. This Review summarizes the broad immunologic roles of autophagy. Furthermore, it uses the autophagic control of Mycobacterium tuberculosis as a paradigm to illustrate the breadth and complexity of the immune effects of autophagy.

MeSH Terms
Adaptive Immunity Animals Autophagy Host-Pathogen Interactions Humans Immunity, Innate Inflammation/pathology Mycobacterium tuberculosis/immunology Phagocytosis Tuberculosis/immunology,microbiology,pathology
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Deretic Vojo
Kimura Tomonori
Timmins Graham
Moseley Pope
Chauhan Santosh
Mandell Michael
References (151)
151 references, click to expand
  1. TRAF6 and A20 regulate lysine 63-linked ubiquitination of Beclin-1 to control TLR4-induced autophagy.
    Sci Signal. 2010;3(123):ra42 PMID: 20501938
  2. TLR-induced PAI-2 expression suppresses IL-1β processing via increasing autophagy and NLRP3 degradation.
    Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):16079-84 PMID: 24043792
  3. Regulation of innate immune signalling pathways by the tripartite motif (TRIM) family proteins.
    EMBO Mol Med. 2011 Sep;3(9):513-27 PMID: 21826793
  4. Regulation of Toll-like receptor signaling by NDP52-mediated selective autophagy is normally inactivated by A20.
    Cell Mol Life Sci. 2012 Mar;69(6):963-79 PMID: 21964925
  5. A role for mitochondria in NLRP3 inflammasome activation.
    Nature. 2011 Jan 13;469(7329):221-5 PMID: 21124315
  6. Autophagy enhances the efficacy of BCG vaccine by increasing peptide presentation in mouse dendritic cells.
    Nat Med. 2009 Mar;15(3):267-76 PMID: 19252503
  7. Human IRGM induces autophagy to eliminate intracellular mycobacteria.
    Science. 2006 Sep 8;313(5792):1438-41 PMID: 16888103
  8. Autophagy is essential for mitochondrial clearance in mature T lymphocytes.
    J Immunol. 2009 Apr 1;182(7):4046-55 PMID: 19299702
  9. Host cell autophagy promotes BK virus infection.
    Virology. 2014 May;456-457:87-95 PMID: 24889228
  10. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages.
    J Cell Biol. 2009 Jul 27;186(2):255-68 PMID: 19635843
  11. In vivo requirement for Atg5 in antigen presentation by dendritic cells.
    Immunity. 2010 Feb 26;32(2):227-39 PMID: 20171125
  12. Low serum vitamin D levels and tuberculosis: a systematic review and meta-analysis.
    Int J Epidemiol. 2008 Feb;37(1):113-9 PMID: 18245055
  13. Structural mechanism of cytosolic DNA sensing by cGAS.
    Nature. 2013 Jun 20;498(7454):332-7 PMID: 23722159
  14. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages.
    Sci Transl Med. 2011 Oct 12;3(104):104ra102 PMID: 21998409
  15. Amino acid starvation induced by invasive bacterial pathogens triggers an innate host defense program.
    Cell Host Microbe. 2012 Jun 14;11(6):563-75 PMID: 22704617
  16. Meta-analysis followed by replication identifies loci in or near CDKN1B, TET3, CD80, DRAM1, and ARID5B as associated with systemic lupus erythematosus in Asians.
    Am J Hum Genet. 2013 Jan 10;92(1):41-51 PMID: 23273568
  17. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway.
    Cell. 2012 Aug 17;150(4):803-15 PMID: 22901810
  18. Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2.
    Mol Cell. 2007 Jan 26;25(2):193-205 PMID: 17244528
  19. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity.
    Immunity. 2007 Jul;27(1):135-44 PMID: 17658277
  20. Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade.
    PLoS Pathog. 2012 Feb;8(2):e1002517 PMID: 22319449
  21. NOD2 enhances the innate response of alveolar macrophages to Mycobacterium tuberculosis in humans.
    Eur J Immunol. 2012 Apr;42(4):880-9 PMID: 22531915
  22. Regulation of SIV antigen-specific CD4+ T cellular immunity via autophagosome-mediated MHC II molecule-targeting antigen presentation in mice.
    PLoS One. 2014;9(3):e93143 PMID: 24671203
  23. ULK1 induces autophagy by phosphorylating Beclin-1 and activating VPS34 lipid kinase.
    Nat Cell Biol. 2013 Jul;15(7):741-50 PMID: 23685627
  24. M. tuberculosis and M. leprae translocate from the phagolysosome to the cytosol in myeloid cells.
    Cell. 2007 Jun 29;129(7):1287-98 PMID: 17604718
  25. Phosphoprotein of human parainfluenza virus type 3 blocks autophagosome-lysosome fusion to increase virus production.
    Cell Host Microbe. 2014 May 14;15(5):564-77 PMID: 24832451
  26. Selective autophagy mediated by autophagic adapter proteins.
    Autophagy. 2011 Mar;7(3):279-96 PMID: 21189453
  27. Autophagy and the effects of its inhibition on varicella-zoster virus glycoprotein biosynthesis and infectivity.
    J Virol. 2014 Jan;88(2):890-902 PMID: 24198400
  28. Selective autophagy of the adaptor protein Bcl10 modulates T cell receptor activation of NF-κB.
    Immunity. 2012 Jun 29;36(6):947-58 PMID: 22658522
  29. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages.
    Cell. 2004 Dec 17;119(6):753-66 PMID: 15607973
  30. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation.
    Immunity. 2012 Aug 24;37(2):223-34 PMID: 22921120
  31. ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages.
    BMC Immunol. 2008;9:35 PMID: 18627610
  32. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway.
    Science. 2013 Feb 15;339(6121):786-91 PMID: 23258413
  33. Crosstalk between the cGAS DNA sensor and Beclin-1 autophagy protein shapes innate antimicrobial immune responses.
    Cell Host Microbe. 2014 Feb 12;15(2):228-38 PMID: 24528868
  34. A LC3-interacting motif in the influenza A virus M2 protein is required to subvert autophagy and maintain virion stability.
    Cell Host Microbe. 2014 Feb 12;15(2):239-47 PMID: 24528869
  35. The class III kinase Vps34 promotes T lymphocyte survival through regulating IL-7Rα surface expression.
    J Immunol. 2011 Nov 15;187(10):5051-61 PMID: 22021616
  36. Organelle membrane proteomics reveals differential influence of mycobacterial lipoglycans on macrophage phagosome maturation and autophagosome accumulation.
    J Proteome Res. 2011 Jan 7;10(1):339-48 PMID: 21105745
  37. p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways.
    J Biol Chem. 2011 Jul 29;286(30):26987-95 PMID: 21646350
  38. Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    Nature. 2012 Nov 1;491(7422):119-24 PMID: 23128233
  39. ESX-1 dependent impairment of autophagic flux by Mycobacterium tuberculosis in human dendritic cells.
    Autophagy. 2012 Sep;8(9):1357-70 PMID: 22885411
  40. Autophagy of intracellular microbes and mitochondria: two sides of the same coin?
    F1000 Biol Rep. 2010 Jun 23;2:null PMID: 20948788
  41. Conditional ablation of HMGB1 in mice reveals its protective function against endotoxemia and bacterial infection.
    Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20699-704 PMID: 24302768
  42. 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
  43. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy.
    Cell. 2013 Jan 17;152(1-2):290-303 PMID: 23332761
  44. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins.
    Mol Cell. 2011 Oct 21;44(2):279-89 PMID: 22017874
  45. Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes.
    J Immunol. 2011 Feb 1;186(3):1564-74 PMID: 21191072
  46. Mycobacterium tuberculosis-driven targeted recalibration of macrophage lipid homeostasis promotes the foamy phenotype.
    Cell Host Microbe. 2012 Nov 15;12(5):669-81 PMID: 23159056
  47. TRIM proteins regulate autophagy and can target autophagic substrates by direct recognition.
    Dev Cell. 2014 Aug 25;30(4):394-409 PMID: 25127057
  48. Sterical hindrance promotes selectivity of the autophagy cargo receptor NDP52 for the danger receptor galectin-8 in antibacterial autophagy.
    Sci Signal. 2013 Feb 5;6(261):ra9 PMID: 23386746
  49. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth.
    Science. 2011 Jul 8;333(6039):228-33 PMID: 21617041
  50. A role for NBR1 in autophagosomal degradation of ubiquitinated substrates.
    Mol Cell. 2009 Feb 27;33(4):505-16 PMID: 19250911
  51. Noncanonical autophagy is required for type I interferon secretion in response to DNA-immune complexes.
    Immunity. 2012 Dec 14;37(6):986-97 PMID: 23219390
  52. Regulatory coordination between two major intracellular homeostatic systems: heat shock response and autophagy.
    J Biol Chem. 2013 May 24;288(21):14959-72 PMID: 23576438
  53. The Atg5 Atg12 conjugate associates with innate antiviral immune responses.
    Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5 PMID: 17709747
  54. Essential role for autophagy in the maintenance of immunological memory against influenza infection.
    Nat Med. 2014 May;20(5):503-10 PMID: 24747745
  55. Autophagy attenuates the adaptive immune response by destabilizing the immunologic synapse.
    Gastroenterology. 2012 Jun;142(7):1493-503.e6 PMID: 22370477
  56. Autophagy proteins stabilize pathogen-containing phagosomes for prolonged MHC II antigen processing.
    J Cell Biol. 2013 Dec 9;203(5):757-66 PMID: 24322427
  57. Autophagy in infection, inflammation and immunity.
    Nat Rev Immunol. 2013 Oct;13(10):722-37 PMID: 24064518
  58. c-di-AMP secreted by intracellular Listeria monocytogenes activates a host type I interferon response.
    Science. 2010 Jun 25;328(5986):1703-5 PMID: 20508090
  59. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria.
    Nat Immunol. 2009 Nov;10(11):1215-21 PMID: 19820708
  60. Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses.
    Immunity. 2010 May 28;32(5):654-69 PMID: 20451412
  61. Endogenous MHC class II processing of a viral nuclear antigen after autophagy.
    Science. 2005 Jan 28;307(5709):593-6 PMID: 15591165
  62. Autophagy regulates phagocytosis by modulating the expression of scavenger receptors.
    Immunity. 2013 Sep 19;39(3):537-47 PMID: 24035364
  63. FOXO3A directs a protective autophagy program in haematopoietic stem cells.
    Nature. 2013 Feb 21;494(7437):323-7 PMID: 23389440
  64. A role for c-FLIP(L) in the regulation of apoptosis, autophagy, and necroptosis in T lymphocytes.
    Cell Death Differ. 2013 Feb;20(2):188-97 PMID: 23175183
  65. Autophagy in thymic epithelium shapes the T-cell repertoire and is essential for tolerance.
    Nature. 2008 Sep 18;455(7211):396-400 PMID: 18701890
  66. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production.
    Nature. 2008 Nov 13;456(7219):264-8 PMID: 18849965
  67. Diverse autophagosome membrane sources coalesce in recycling endosomes.
    Cell. 2013 Sep 12;154(6):1285-99 PMID: 24034251
  68. Vitamin D rescues impaired Mycobacterium tuberculosis-mediated tumor necrosis factor release in macrophages of HIV-seropositive individuals through an enhanced Toll-like receptor signaling pathway in vitro.
    Infect Immun. 2013 Jan;81(1):2-10 PMID: 23071135
  69. A comprehensive analysis of shared loci between systemic lupus erythematosus (SLE) and sixteen autoimmune diseases reveals limited genetic overlap.
    PLoS Genet. 2011 Dec;7(12):e1002406 PMID: 22174698
  70. TBK1 kinase addiction in lung cancer cells is mediated via autophagy of Tax1bp1/Ndp52 and non-canonical NF-κB signalling.
    PLoS One. 2012;7(11):e50672 PMID: 23209807
  71. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1.
    Nat Cell Biol. 2011 Feb;13(2):132-41 PMID: 21258367
  72. Autophagy in antigen-presenting cells results in presentation of citrullinated peptides to CD4 T cells.
    J Exp Med. 2011 Dec 19;208(13):2625-32 PMID: 22162830
  73. The origin of the autophagosomal membrane.
    Nat Cell Biol. 2010 Sep;12(9):831-5 PMID: 20811355
  74. 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
  75. Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor.
    Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5514-9 PMID: 16540544
  76. Genetic variants at CD28, PRDM1 and CD2/CD58 are associated with rheumatoid arthritis risk.
    Nat Genet. 2009 Dec;41(12):1313-8 PMID: 19898481
  77. Genetic variation in the autophagy gene ULK1 and risk of Crohn's disease.
    Inflamm Bowel Dis. 2011 Jun;17(6):1392-7 PMID: 21560199
  78. 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
  79. Autophagy and cellular immune responses.
    Immunity. 2013 Aug 22;39(2):211-27 PMID: 23973220
  80. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism.
    Nat Cell Biol. 2011 Sep;13(9):1016-23 PMID: 21892142
  81. Plasma cells require autophagy for sustainable immunoglobulin production.
    Nat Immunol. 2013 Mar;14(3):298-305 PMID: 23354484
  82. Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection.
    Cell Host Microbe. 2014 Feb 12;15(2):214-27 PMID: 24528867
  83. STING is a direct innate immune sensor of cyclic di-GMP.
    Nature. 2011 Oct 27;478(7370):515-8 PMID: 21947006
  84. Genetic variants in autophagy-related genes and granuloma formation in a cohort of surgically treated Crohn's disease patients.
    J Crohns Colitis. 2012 Feb;6(1):43-50 PMID: 22261526
  85. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling.
    Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2770-5 PMID: 19196953
  86. Toll-like receptors control autophagy.
    EMBO J. 2008 Apr 9;27(7):1110-21 PMID: 18337753
  87. mTOR inhibits autophagy by controlling ULK1 ubiquitylation, self-association and function through AMBRA1 and TRAF6.
    Nat Cell Biol. 2013 Apr;15(4):406-16 PMID: 23524951
  88. Vitamin D3 induces autophagy in human monocytes/macrophages via cathelicidin.
    Cell Host Microbe. 2009 Sep 17;6(3):231-43 PMID: 19748465
  89. Antiviral autophagy restrictsRift Valley fever virus infection and is conserved from flies to mammals.
    Immunity. 2014 Jan 16;40(1):51-65 PMID: 24374193
  90. NDP52, a novel autophagy receptor for ubiquitin-decorated cytosolic bacteria.
    Autophagy. 2010 Feb;6(2):288-9 PMID: 20104023
  91. Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy.
    PLoS Pathog. 2012;8(5):e1002689 PMID: 22589721
  92. Defects in mitochondrial clearance predispose human monocytes to interleukin-1β hypersecretion.
    J Biol Chem. 2014 Feb 21;289(8):5000-12 PMID: 24356959
  93. Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response.
    Proc Natl Acad Sci U S A. 2009 Dec 8;106(49):20842-6 PMID: 19926846
  94. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome.
    Nat Immunol. 2011 Mar;12(3):222-30 PMID: 21151103
  95. NLRP6 inflammasome orchestrates the colonic host-microbial interface by regulating goblet cell mucus secretion.
    Cell. 2014 Feb 27;156(5):1045-59 PMID: 24581500
  96. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation.
    Nat Med. 2010 Jan;16(1):90-7 PMID: 19966812
  97. Cytoplasmic STAT3 represses autophagy by inhibiting PKR activity.
    Mol Cell. 2012 Dec 14;48(5):667-80 PMID: 23084476
  98. Functional variant in the autophagy-related 5 gene promotor is associated with childhood asthma.
    PLoS One. 2012;7(4):e33454 PMID: 22536318
  99. Endogenous HMGB1 regulates autophagy.
    J Cell Biol. 2010 Sep 6;190(5):881-92 PMID: 20819940
  100. Human papillomavirus infection is inhibited by host autophagy in primary human keratinocytes.
    Virology. 2013 Mar 1;437(1):12-9 PMID: 23290079
  101. Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria.
    Nat Cell Biol. 2010 Dec;12(12):1154-65 PMID: 21102437
  102. Rubella virus perturbs autophagy.
    Med Microbiol Immunol. 2014 Oct;203(5):323-31 PMID: 24824868
  103. Dectin-1 pathway activates robust autophagy-dependent unconventional protein secretion in human macrophages.
    J Immunol. 2014 Jun 15;192(12):5952-62 PMID: 24808366
  104. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.
    Nature. 2007 Jun 7;447(7145):661-78 PMID: 17554300
  105. Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion.
    Nature. 2012 Feb 16;482(7385):414-8 PMID: 22246324
  106. Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.
    Nat Genet. 2009 Nov;41(11):1234-7 PMID: 19838193
  107. The LRR and RING domain protein LRSAM1 is an E3 ligase crucial for ubiquitin-dependent autophagy of intracellular Salmonella Typhimurium.
    Cell Host Microbe. 2012 Dec 13;12(6):778-90 PMID: 23245322
  108. The autophagy regulator Rubicon is a feedback inhibitor of CARD9-mediated host innate immunity.
    Cell Host Microbe. 2012 Mar 15;11(3):277-89 PMID: 22423967
  109. Costimulatory blockade-induced allograft survival requires Beclin1.
    Am J Transplant. 2014 Mar;14(3):545-53 PMID: 24502356
  110. Mycobacterium tuberculosis eis regulates autophagy, inflammation, and cell death through redox-dependent signaling.
    PLoS Pathog. 2010;6(12):e1001230 PMID: 21187903
  111. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy.
    Science. 2011 Jan 28;331(6016):456-61 PMID: 21205641
  112. Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.
    Science. 2014 Jan 17;343(6168):313-7 PMID: 24310610
  113. The role of Atg proteins in autophagosome formation.
    Annu Rev Cell Dev Biol. 2011;27:107-32 PMID: 21801009
  114. Specific T cells restore the autophagic flux inhibited by Mycobacterium tuberculosis in human primary macrophages.
    J Infect Dis. 2012 May 1;205(9):1425-35 PMID: 22457295
  115. T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis.
    Immunity. 2007 Sep;27(3):505-17 PMID: 17892853
  116. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes.
    Immunity. 2007 Jan;26(1):79-92 PMID: 17182262
  117. NLRP4 negatively regulates autophagic processes through an association with beclin1.
    J Immunol. 2011 Feb 1;186(3):1646-55 PMID: 21209283
  118. cGAS produces a 2'-5'-linked cyclic dinucleotide second messenger that activates STING.
    Nature. 2013 Jun 20;498(7454):380-4 PMID: 23722158
  119. Autophagy is essential for effector CD8(+) T cell survival and memory formation.
    Nat Immunol. 2014 Dec;15(12):1152-61 PMID: 25362489
  120. Cyclic dinucleotides trigger ULK1 (ATG1) phosphorylation of STING to prevent sustained innate immune signaling.
    Cell. 2013 Oct 24;155(3):688-98 PMID: 24119841
  121. Genome-wide association scan in women with systemic lupus erythematosus identifies susceptibility variants in ITGAM, PXK, KIAA1542 and other loci.
    Nat Genet. 2008 Feb;40(2):204-10 PMID: 18204446
  122. Autophagy controls IL-1beta secretion by targeting pro-IL-1beta for degradation.
    J Biol Chem. 2011 Mar 18;286(11):9587-97 PMID: 21228274
  123. The B cell receptor governs the subcellular location of Toll-like receptor 9 leading to hyperresponses to DNA-containing antigens.
    Immunity. 2008 Jun;28(6):799-809 PMID: 18513998
  124. Autophagy protects against active tuberculosis by suppressing bacterial burden and inflammation.
    Proc Natl Acad Sci U S A. 2012 Nov 13;109(46):E3168-76 PMID: 23093667
  125. Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties.
    Immunity. 2010 Mar 26;32(3):329-41 PMID: 20206555
  126. Cell biology of mycobacterium tuberculosis phagosome.
    Annu Rev Cell Dev Biol. 2004;20:367-94 PMID: 15473845
  127. Mycobacterial induction of autophagy varies by species and occurs independently of mammalian target of rapamycin inhibition.
    J Biol Chem. 2012 Apr 13;287(16):12668-78 PMID: 22275355
  128. A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells.
    Nature. 2008 Nov 13;456(7219):259-63 PMID: 18849966
  129. Autophagy-based unconventional secretory pathway for extracellular delivery of IL-1β.
    EMBO J. 2011 Nov 30;30(23):4701-11 PMID: 22068051
  130. Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls.
    Nature. 2010 Apr 1;464(7289):713-20 PMID: 20360734
  131. Toll-like receptor signalling in macrophages links the autophagy pathway to phagocytosis.
    Nature. 2007 Dec 20;450(7173):1253-7 PMID: 18097414
  132. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction.
    Nat Immunol. 2012 Mar;13(3):255-63 PMID: 22286270
  133. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4.
    EMBO J. 2007 Apr 4;26(7):1749-60 PMID: 17347651
  134. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry.
    Nat Immunol. 2010 Jan;11(1):55-62 PMID: 19898471
  135. Shigella phagocytic vacuolar membrane remnants participate in the cellular response to pathogen invasion and are regulated by autophagy.
    Cell Host Microbe. 2009 Aug 20;6(2):137-49 PMID: 19683680
  136. Neutral lipid stores and lipase PNPLA5 contribute to autophagosome biogenesis.
    Curr Biol. 2014 Mar 17;24(6):609-20 PMID: 24613307
  137. The autophagy protein Atg7 is essential for hematopoietic stem cell maintenance.
    J Exp Med. 2011 Mar 14;208(3):455-67 PMID: 21339326
  138. Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis.
    Cell. 2010 Mar 5;140(5):731-43 PMID: 20211141
  139. Macroautophagy substrates are loaded onto MHC class II of medullary thymic epithelial cells for central tolerance.
    J Exp Med. 2013 Feb 11;210(2):287-300 PMID: 23382543
  140. Receptor interacting protein kinase 2-mediated mitophagy regulates inflammasome activation during virus infection.
    Nat Immunol. 2013 May;14(5):480-8 PMID: 23525089
  141. Autophagy in immunity and inflammation.
    Nature. 2011 Jan 20;469(7330):323-35 PMID: 21248839
  142. IL-10 inhibits the starvation induced autophagy in macrophages via class I phosphatidylinositol 3-kinase (PI3K) pathway.
    Mol Immunol. 2011 Jan;48(4):720-7 PMID: 21095008
  143. Autophagosomes, phagosomes, autolysosomes, phagolysosomes, autophagolysosomes... wait, I'm confused.
    Autophagy. 2014 Apr;10(4):549-51 PMID: 24657946
  144. Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes.
    Cell Host Microbe. 2009 Oct 22;6(4):367-80 PMID: 19837376
  145. Association between variants of PRDM1 and NDP52 and Crohn's disease, based on exome sequencing and functional studies.
    Gastroenterology. 2013 Aug;145(2):339-47 PMID: 23624108
  146. Amphisomal route of MHC class I cross-presentation in bacteria-infected dendritic cells.
    J Immunol. 2013 Mar 15;190(6):2791-806 PMID: 23418629
  147. Autophagy-dependent viral recognition by plasmacytoid dendritic cells.
    Science. 2007 Mar 9;315(5817):1398-401 PMID: 17272685
  148. Autophagy defends cells against invading group A Streptococcus.
    Science. 2004 Nov 5;306(5698):1037-40 PMID: 15528445
  149. The ubiquitin ligase parkin mediates resistance to intracellular pathogens.
    Nature. 2013 Sep 26;501(7468):512-6 PMID: 24005326
  150. Recessive mutations in EPG5 cause Vici syndrome, a multisystem disorder with defective autophagy.
    Nat Genet. 2013 Jan;45(1):83-7 PMID: 23222957
  151. Autophagy adaptor protein p62/SQSTM1 and autophagy-related gene Atg5 mediate autophagosome formation in response to Mycobacterium tuberculosis infection in dendritic cells.
    PLoS One. 2013;8(12):e86017 PMID: 24376899
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
1558-8238
DOI
10.1172/JCI73945
Published
2015-01-00
Epub
2015-00-02
Pages
75-84
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC4350422
Subset
IM
Grants
NIAID NIH HHS · R01 AI042999 · United States
NCATS NIH HHS · UL1 TR001449 · United States
NIAID NIH HHS · R37 AI042999 · United States
NIAID NIH HHS · R01 AI111935 · United States
NIAID NIH HHS · AI111935 · United States
NIAID NIH HHS · AI042999 · United States
NCATS NIH HHS · UL1 TR000041 · United States
External Links
PubMed source DOI: 10.1172/JCI73945 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2