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  • Review Article
  • Published:

Unveiling the roles of autophagy in innate and adaptive immunity

Nature Reviews Immunology volume 7, pages 767–777 (2007)Cite this article

Key Points

  • Autophagy has a role in degrading intracellular bacteria, parasites and viruses.

  • Intracellular pathogens have strategies to subvert or evade the autophagy pathway.

  • Autophagy has a role in innate immune signalling by delivering viral nucleic acids to endosomal Toll-like receptors.

  • Autophagy is active in antigen-presenting cells and is involved in MHC class II presentation of certain endogenous antigens.

  • Immune signalling molecules that are important in the control of viruses, parasites and intracellular bacteria activate autophagy.

  • Autophagy is involved in regulating T-cell homeostasis.

  • Autophagy genes are strongly linked to susceptibility to Crohn's disease, a form of inflammatory bowel disease.

Abstract

Cells digest portions of their interiors in a process known as autophagy to recycle nutrients, remodel and dispose of unwanted cytoplasmic constituents. This ancient pathway, conserved from yeast to humans, is now emerging as a central player in the immunological control of bacterial, parasitic and viral infections. The process of autophagy may degrade intracellular pathogens, deliver endogenous antigens to MHC-class-II-loading compartments, direct viral nucleic acids to Toll-like receptors and regulate T-cell homeostasis. This Review describes the mechanisms of autophagy and highlights recent advances relevant to the role of autophagy in innate and adaptive immunity.

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Figure 1: Cellular events in autophagy.
Figure 2: Molecular events in autophagy.
Figure 3: Autophagy eliminates intracellular microorganisms.
Figure 4: Functions of autophagy in innate and adaptive immunity during infection with intracellular pathogens.

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References

  1. Klionsky, D. J. & Emr, S. D. Autophagy as a regulated pathway of cellular degradation. Science 290, 1717–1721 (2000).

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Lum, J. J., DeBerardinis, R. J. & Thompson, C. B. Autophagy in metazoans: cell survival in the land of plenty. Nature Rev. Mol. Cell. Biol. 6, 439–448 (2005).

    CAS  Google Scholar 

  3. Levine, B. & Klionsky, D. J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463–477 (2004).

    CAS  PubMed  Google Scholar 

  4. Shintani, T. & Klionsky, D. J. Autophagy in health and disease: a double-edged sword. Science 306, 990–995 (2004). References 1–4 provide excellent general reviews on autophagy and its molecular mechanisms, physiological functions and roles in disease.

    CAS  PubMed Central  PubMed  Google Scholar 

  5. Deretic, V. Autophagy in innate and adaptive immunity. Trends. Immunol. 26, 523–528 (2005).

    CAS  PubMed  Google Scholar 

  6. Schmid, D., Dengjel, J., Schoor, O., Stevanovic, S. & Munz, C. Autophagy in innate and adaptive immunity against intracellular pathogens. J. Mol. Med. 84, 1–9 (2006).

    Google Scholar 

  7. Deretic, V. Autophagy as an immune defense mechanism. Curr. Opin. Immunol 18, 375–382 (2006).

    CAS  PubMed  Google Scholar 

  8. Andrade, R. M., Wessendarp, M., Gubbels, M. J., Striepen, B. & Subauste, C. S. CD40 induces macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-containing vacuoles and lysosomes. J. Clin. Invest. 116, 2366–2377 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  9. Ling, Y. M. et al. Vacuolar and plasma membrane stripping and autophagic elimination of Toxoplasma gondii in primed effector macrophages. J. Exp. Med. 203, 2063–2071 (2006). References 8–9 provide the first demonstrations that autophagy has a role in the elimination of parasites.

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Amano, A., Nakagawa, I. & Yoshimori, T. Autophagy in innate immunity against intracellular bacteria. J. Biochem. 140, 161–166 (2006).

    CAS  PubMed  Google Scholar 

  11. Menéndez-Benito, V. & Neefjes, J. Autophagy in MHC class II presentation: sampling from within. Immunity 26, 1–3 (2007).

    PubMed  Google Scholar 

  12. Lee, H. K., Lund, J. M., Ramanathan, B., Mizushima, N. & Iwasaki, A. Autophagy-dependent viral recognition by plasmacytoid dendritic cell. Science 315, 1398–1401 (2007). This is a landmark paper describing a new function of autophagy in innate immunity; this paper provides the first evidence that the autophagic machinery delivers viral genetic material to endosomal TLRs.

    CAS  PubMed  Google Scholar 

  13. Pua, H. H., Dzhagalov, I., Chuck, M., Mizushima, N. & He, Y. W. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med. 204, 25–31 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Li, C. et al. Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J. Immunol. 177, 5163–5168 (2006).

    CAS  PubMed  Google Scholar 

  15. Qu, X. et al. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128, 931–946 (2007). This paper describes a cell-autonomous essential role for autophagy in generating signals for apoptotic cell corpse removal, raising the possibility that autophagy may help to prevent inflammation and autoimmunity.

    CAS  PubMed  Google Scholar 

  16. Hampe, J. et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nature Genet. 39, 207–211 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Rioux, J. D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genet. 39, 596–604 (2007).

    CAS  PubMed  Google Scholar 

  18. Prescott, N. J. et al. A nonsynonymous SNP in ATG16L predisposes to ileal Crohn's disease and is independent of CARD15 and IBD5. Gastroenterology 132, 1665–1671 (2007).

    CAS  PubMed  Google Scholar 

  19. The Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447, 661–678 (2007).

    Google Scholar 

  20. Parkes, M. et al. Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility. Nature Genet. 39, 830–832 (2007). References 15–20 provide the first genetic evidence that human autophagy genes are linked to susceptibility to inflammatory disease. They demonstrate that polymorphisms in IRGM and ATG16L are strongly associated with Crohn's disease.

    Article  CAS  PubMed  Google Scholar 

  21. Meijer, A. J. & Codogno, P. Regulation and role of autophagy in mammalian cells. Int. J. Biochem. Cell. Biol. 36, 2445–2462 (2004).

    CAS  PubMed  Google Scholar 

  22. Meijer, A. J. & Codogno, P. Signalling and autophagy regulation in health and disease. Mol. Aspects. Med. 27, 411–425 (2006). References 21–22 provide excellent, comprehensive reviews of the signalling pathways that regulate autophagy.

    CAS  PubMed  Google Scholar 

  23. Byfield, M. P., Murray, J. T. & Backer, J. M. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J. Biol. Chem. 280, 33076–33082 (2005).

    CAS  PubMed  Google Scholar 

  24. Nobukuni, T. et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc. Natl Acad. Sci. USA 102, 14238–14243 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Kihara, A., Kabeya, Y., Ohsumi, Y. & Yoshimori, T. Beclin–phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2, 330–335 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  26. Liang, C. et al. Autophagic and tumour suppressor activity of a novel Beclin 1-binding protein UVRAG. Nature Cell Biol. 8, 688–699 (2006).

    CAS  PubMed  Google Scholar 

  27. Fimia, G. M. et al. Ambra1 regulates autophagy and development of the nervous system. Nature 447, 1121–1125 (2007).

    CAS  PubMed  Google Scholar 

  28. Pattingre, S. et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927–939 (2005).

    CAS  PubMed  Google Scholar 

  29. Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471–484 (2006).

    CAS  PubMed  Google Scholar 

  30. Seglen, P. O. & Gordon, P. B. 3-Methyladenine: specific inhibitor of autophagic/lysosomal protein degradation in isolated rat hepatocytes. Proc. Natl Acad. Sci. USA 79, 1889–1892 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Klionsky, D. J. et al. A unified nomenclature for yeast autophagy-related genes. Dev. Cell 5, 539–545 (2003).

    CAS  PubMed  Google Scholar 

  32. Ohsumi, Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nature Rev. Mol. Cell Biol. 2, 211–216 (2001).

    CAS  Google Scholar 

  33. Yorimitsu, T. & Klionsky, D. J. Autophagy: molecular machinery for self-eating. Cell Death Differ. 12 (Suppl. 2), 1542–1552 (2005).

    CAS  PubMed  Google Scholar 

  34. Suzuki, K. & Ohsumi, Y. Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett. 581, 2156–61.(2007).

    CAS  PubMed  Google Scholar 

  35. Bjorkoy, G., Lamark, T. & Johansen, T. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell. Biol. 171, 603–614 (2005).

    PubMed Central  PubMed  Google Scholar 

  36. Rikihisa, Y. Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae. Anat. Rec. 208, 319–327 (1984).

    CAS  PubMed  Google Scholar 

  37. Kirkegaard, K., Taylor, M. P. & Jackson, W. T. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nature Rev. Microbiol. 2, 301–314 (2004). This is an excellent review of the complex relationships between autophagy and microorganisms, with in-depth coverage of the topic of subversion of autophagy by microbial pathogens.

    CAS  Google Scholar 

  38. Levine, B. Eating oneself and uninvited guests; autophagy-related pathways in cellular defense. Cell 120, 159–162 (2005).

    CAS  PubMed  Google Scholar 

  39. Fratti, R. A., Backer, J. M., Gruenberg, J., Corvera, S. & Deretic, V. Role of phosphatidylinositol 3-kinase and Rab5 effectors in phagosomal biogenesis and mycobacterial phagosome maturation arrest. J. Cell. Biol. 154, 631–644 (2001).

    CAS  PubMed Central  PubMed  Google Scholar 

  40. Vergne, I., Chua, J. & Deretic, V. Mycobacterium tuberculosis phagosome maturation arrest: selective targeting of PI3P-dependent membrane trafficking. Traffic 4, 600–606 (2003).

    CAS  PubMed  Google Scholar 

  41. Vergne, I. et al. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol. Biol. Cell 15, 751–760 (2004).

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Gutierrez, M. G. et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753–766 (2004).

    CAS  PubMed  Google Scholar 

  43. Ogawa, M. et al. Escape of intracellular Shigella from autophagy. Science 307, 727–731 (2005).

    CAS  PubMed  Google Scholar 

  44. Nakagawa, I. et al. Autophagy defends cells against invading group A Streptococcus. Science 306, 1037–1040 (2004). References 42–44 are landmark papers that formed the foundation for the principle that autophagy is important in defence against intracellular bacterial pathogens (such as M. tuberculosis and Shigella spp.) and extracellular bacterial pathogens that invade the cytosol (such as group A Streptococcus).

    CAS  PubMed  Google Scholar 

  45. Singh, S. B., Davis, A. S., Taylor, G. A. & Deretic, V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438–1441 (2006). This paper identified an important signalling mechanism (involving IRGM) that activates autophagy-dependent control of mycobacteria.

    CAS  PubMed  Google Scholar 

  46. Rich, K. A., Burkett, C. & Webster, P. Cytoplasmic bacteria can be targets for autophagy. Cell. Microbiol. 5, 455–468 (2003).

    CAS  PubMed  Google Scholar 

  47. Py, B. F., Lipinski, M. M. & Yuan, J. Autophagy limits Listeria monocytogenes intracellular growth in the early phase of primary infection. Autophagy 3, 117–125 (2007).

    CAS  PubMed  Google Scholar 

  48. Birmingham, C. L., Smith, A. C., Bakowski, M. A., Yoshimori, T. & Brumell, J. H. Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J. Biol. Chem. 281, 11374–11383 (2006).

    CAS  PubMed  Google Scholar 

  49. Checroun, C., Wehrly, T. D., Fischer, E. R., Hayes, S. F. & Celli, J. Autophagy-mediated reentry of Francisella tularensis into the endocytic compartment after cytoplasmic replication. Proc. Natl Acad. Sci. USA 103, 14578–14583 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  50. Yamamoto, A., Cremona, M. L. & Rothman, J. E. Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway. J. Cell Biol. 172, 719–731 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  51. Ogawa, M. & Sasakawa, C. Intracellular survival of Shigella. Cell. Microbiol. 8, 177–184 (2006).

    CAS  PubMed  Google Scholar 

  52. Balachandran, P. et al. The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence. J. Clin. Invest. 117, 419–427 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

  53. Djavaheri-Mergny, M. et al. NF-κB activation represses tumor necrosis factor-α-induced autophagy. J. Biol. Chem. 281, 30373–30382 (2006).

    CAS  PubMed  Google Scholar 

  54. Scherz-Shouvai, R. et al. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 26, 1749–1760 (2007).

    Google Scholar 

  55. Talloczy, Z., Virgin, H. W. & Levine, B. PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2, 24–29 (2006).

    CAS  PubMed  Google Scholar 

  56. Jackson, W. T. et al. Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol. 3, e156 (2005).

    PubMed Central  PubMed  Google Scholar 

  57. Prentice, E., Jerome, W. G., Yoshimori, T., Mizushima, N. & Denison, M. R. Coronavirus replication complex formation utilizes components of cellular autophagy. J. Biol. Chem. 279, 10136–10141 (2004). References 56–57 indicate a role for components of the autophagic machinery in the establishment of viral replication complexes.

    CAS  PubMed  Google Scholar 

  58. Cherry, S. et al. COPI activity coupled with fatty acid biosynthesis is required for viral replication. PLoS Pathog. 2, e102 (2006).

    PubMed Central  PubMed  Google Scholar 

  59. Zhang, H. et al. Cellular autophagy machinery is not required for vaccinia virus replication and maturation. Autophagy 2, 91–95 (2006).

    PubMed  Google Scholar 

  60. Liu, Y. et al. Autophagy regulates programmed cell death during the plant innate immune response. Cell 121, 567–577 (2005). This paper provided the first demonstration that loss-of-function mutations of autophagy genes increases susceptibility to microbial infection in vivo.

    CAS  PubMed  Google Scholar 

  61. Liang, X. H. et al. Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J. Virol. 72, 8586–8596 (1998). This paper provided the first demonstration of an antimicrobial effect of an autophagy gene.

    CAS  PubMed Central  PubMed  Google Scholar 

  62. Orvedahl, A. et al. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1, 23–35 (2007). This paper provided the first evidence suggesting that autophagy inhibition is a mechanism by which viruses evade innate immunity and cause disease.

    CAS  PubMed  Google Scholar 

  63. Levine, B. in Autophagy in Immunity and Infection: a novel immune effector (ed. Deretic, V.) 227–241 (Wiley-VCH Weinheim, Germany 2006).

    Google Scholar 

  64. Kawai, T. & Akira, S. Innate immune recognition of viral infection. Nature Immunol. 7, 131–137 (2006).

    CAS  Google Scholar 

  65. Lund, J., Sato, A., Akira, S., Medzhitov, R. & Iwasaki, A. Toll-like receptor 9-mediated recognition of herpes simplex virus-2 by plasmacytoid dendritic cells. J. Exp. Med. 198, 513–520 (2003).

    CAS  PubMed Central  PubMed  Google Scholar 

  66. Brazil, M. I., Weiss, S. & Stockinger, B. Excessive degradation of intracellular protein in macrophages prevents presentation in the context of major histocompatibility complex class II molecules. Eur. J. Immunol. 27, 1506–1514 (1997).

    CAS  PubMed  Google Scholar 

  67. Nimmerjahn, F. et al. Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy. Eur. J. Immunol. 33, 1250–1259 (2003).

    CAS  PubMed  Google Scholar 

  68. Dorfel, D. et al. Processing and presentation of HLA class I and II epitopes by dendritic cells after transfection with in vitro-transcribed MUC1 RNA. Blood 105, 3199–3205 (2005).

    PubMed  Google Scholar 

  69. Dengjel, J. et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc. Natl Acad. Sci. USA 102, 7922–7927 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Paludan, C. et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307, 593–596 (2005). This paper provided the first genetic evidence that autophagy components can be required for efficient MHC class II presentation of an endogenous antigen.

    CAS  PubMed  Google Scholar 

  71. Mizushima, N., Yamamoto, A., Matsui, M., Yoshimori, T. & Ohsumi, Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol. Biol. Cell 15, 1101–1111 (2004). This paper describes the characterization of transgenic autophagy reporter mice (a tool that has greatly facilitated the study of autophagy in vivo ) and the presence of high levels of autophagy in neonatal thymic epithelial cells.

    CAS  PubMed Central  PubMed  Google Scholar 

  72. Taylor, G. S. et al. A role for intercellular antigen transfer in the recognition of EBV-transformed B cell lines by EBV nuclear antigen-specific CD4+ T cells. J. Immunol. 177, 3746–3756 (2006).

    CAS  PubMed  Google Scholar 

  73. Schmid, D., Pypaert, M. & Munz, C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26, 79–92 (2007). This paper provided the first evidence that autophagy occurs constitutively in antigen-presenting cells and also demonstrated that presentation of an influenza virus antigen can be enhanced by specifically targeting it to autophagosomes. The latter finding has important implications for vaccine design.

    CAS  PubMed  Google Scholar 

  74. Massey, A. C., Zhang, C. & Cuervo, A. M. Chaperone-mediated autophagy in aging and disease. Curr. Top. Dev. Biol. 73, 205–235 (2006).

    CAS  PubMed  Google Scholar 

  75. Cuervo, A. M. Autophagy: many paths to the same end. Mol. Cell. Biochem. 263, 55–72 (2004).

    CAS  PubMed  Google Scholar 

  76. Zhou, D. et al. Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity 22, 571–581 (2005).

    CAS  PubMed  Google Scholar 

  77. Talloczy, Z. et al. Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway. Proc. Natl Acad. Sci. USA 99, 190–195 (2002). This paper demonstrated that the IFN-inducible, antiviral signalling molecule PKR is required for virus-induced autophagy.

    CAS  PubMed  Google Scholar 

  78. Inbal, B., Bialik, S., Sabanay, I., Shani, G. & Kimchi, A. DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death. J. Cell. Biol. 157, 455–468 (2002).

    CAS  PubMed Central  PubMed  Google Scholar 

  79. Pyo, J. O. et al. Essential roles of Atg5 and FADD in autophagic cell death: dissection of autophagic cell death into vacuole formation and cell death. J. Biol. Chem. 280, 20722–20729 (2005).

    CAS  PubMed  Google Scholar 

  80. Jia, G., Cheng, G., Gangahar, D. M. & Agrawal, D. K. Insulin-like growth factor-1 and TNF-α regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells. Immunol. Cell Biol. 84, 448–454 (2006).

    CAS  PubMed  Google Scholar 

  81. Subauste, C., Andrade, R. & Wessendarp, M. CD40–TRAF6 and autophagy-dependent anti-microbial activity in macrophages. Autophagy 3, 245–248 (2007).

    CAS  PubMed  Google Scholar 

  82. Wright, K., Ward, S. G., Kolios, G. & Westwick, J. Activation of phosphatidylinositol 3-kinase by interleukin-13. An inhibitory signal for inducible nitric-oxide synthase expression in epithelial cell line HT-29. J. Biol. Chem. 272, 12626–12633 (1997).

    CAS  PubMed  Google Scholar 

  83. Arico, S. et al. The tumor suppressor PTEN positively regulates macroautophagy by inhibiting the phosphatidylinositol 3-kinase/protein kinase B pathway. J. Biol. Chem. 276, 35243–35246 (2001).

    CAS  PubMed  Google Scholar 

  84. Petiot, A., Ogier-Denis, E., Blommaart, E. F., Meijer, A. J. & Codogno, P. Distinct classes of phosphatidylinositol 3′-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J. Biol. Chem. 275, 992–998 (2000).

    CAS  PubMed  Google Scholar 

  85. Gale, M. Jr & Katze, M. G. Molecular mechanisms of interferon resistance mediated by viral-directed inhibition of PKR, the interferon-induced protein kinase. Pharmacol. Ther. 78, 29–46 (1998).

    CAS  PubMed  Google Scholar 

  86. Harris, J. et al. Autophagy is an effector of Th1–Th2 polarization: Th2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity (in the press).

  87. Taylor, G. A., Feng, C. G. & Sher, A. p47 GTPases: regulators of immunity to intracellular pathogens. Nature Rev. Immunol. 4, 100–109 (2004).

    CAS  Google Scholar 

  88. Levine, B. & Yuan, J. Autophagy in cell death: an innocent convict? J. Clin. Invest. 115, 2679–2688 (2005).

    CAS  PubMed Central  PubMed  Google Scholar 

  89. Yoshimori, T. Autophagy: paying Charon's toll. Cell 128, 833–836 (2007).

    CAS  PubMed  Google Scholar 

  90. Espert, L. et al. Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J. Clin. Invest. 116, 2161–2172 (2006).

    CAS  PubMed Central  PubMed  Google Scholar 

  91. Maderna, P. & Godson, C. Phagocytosis of apoptotic cells and the resolution of inflammation. Biochim. Biophys. Acta 1639, 141–151 (2003).

    CAS  PubMed  Google Scholar 

  92. Grossmayer, G. E. et al. Removal of dying cells and systemic lupus erythematosus. Mod. Rheumatol. 15, 383–390 (2005).

    PubMed  Google Scholar 

  93. Gaipl, U. S. et al. Inefficient clearance of dying cells and autoreactivity. Curr. Top. Microbiol. Immunol. 305, 161–176 (2006).

    CAS  PubMed  Google Scholar 

  94. Sartor, R. S. Mechanisms of disease pathogenesis: pathogenesis of Crohn's disease and ulcerative colitis. Nature Clin. Pract. Gastroenterol. Hepatol. 3, 390–407 (2006).

    CAS  Google Scholar 

  95. Baumgart, D. C. & Carding, S. R. Inflammatory bowel disease: cause and immunobiology. Lancet 369, 1627–1640 (2007).

    CAS  PubMed  Google Scholar 

  96. Xu, Y. et al. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27, 135–144 (2007).

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

The original work from the authors' laboratories was supported by the National Institutes of Health, USA (V.D. and B.L.) and the Ellison Medical Foundation (B.L.).

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Authors and Affiliations

  1. Departments of Internal Medicine and Microbiology, University of Texas Southwestern Medical Center, Dallas, 75390, Texas, USA

    Beth Levine

  2. Departments of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, 87131, New Mexico, USA

    Vojo Deretic

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Glossary

Lysosomal degradation

The digestion of macromolecules in lysosomal organelles, which are the terminal organelles of degradative pathways, such as phagosomal or endosomal and autophagy pathways.

Autophagy

Any process involving degradative delivery of a portion of the cytoplasm to the lysosome that does not involve direct transport through the endocytic or vacuolar protein sorting pathways.

Xenophagy

The selective degradation of microorganisms (such as bacteria, fungi, parasites or viruses) through an autophagy-related mechanism.

Macroautophagy

(Also known as autophagy). The largely non-specific autophagic sequestration of cytoplasm into a double- or multiple-membrane-delimited compartment (an autophagosome) of non-lysosomal origin. Note that certain proteins, organelles and pathogens may be selectively degraded via macroautophagy.

Microautophagy

The uptake and degradation of cytoplasm by invagination of the lysosomal membrane.

Chaperone-mediated autophagy

The import and degradation of soluble cytosolic proteins by chaperone-dependent, direct translocation across the lysosomal membrane.

Small interfering RNA

(siRNA). Synthetic RNA molecules of 19–23 nucleotides that are used to 'knockdown' (that is, silence the expression of) a specific gene. This is known as RNA interference (RNAi) and is mediated by the sequence-specific degradation of mRNA.

Proteasome

A giant multicatalytic protease resident to the cytosol and the nucleus.

Peptidome

The repertoire of peptides that is presented by antigen-presenting molecules.

Positive selection

The process in the thymus that selects thymocytes expressing T-cell receptors that have the ability to interact with self MHC molecules.

Negative selection

The process in the thymus that eliminates T cells that express T-cell receptors with high affinity for self antigens.

T helper 1 cell

(TH1 cell). The term used for a CD4+ T cell that has differentiated into a cell that produces the cytokines interferon-γ, lymphotoxin-α and tumour-necrosis factor, and supports cell-mediated immunity.

T helper 2 cell

(TH2 cell). The term used for a CD4+ T cell that has differentiated into a cell that produces interleukin-4 (IL-4), IL-5 and IL1-3, supports humoral immunity and downregulates TH1-cell responses.

p47 GTPase family

A group of 47–48-kDa proteins that are produced in response to interferons (IFNs) and that are involved in resistance to intracellular protozoa, bacteria and viruses. Members of this family include IFNγ-induced GTPase (IGTP), immunity-related GTPase family, M (IRGM; also known as LRG47) and T-cell-specific GTPase (TGTP).

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Levine, B., Deretic, V. Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7, 767–777 (2007). https://doi.org/10.1038/nri2161

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