{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T14:53:52Z","timestamp":1778252032884,"version":"3.51.4"},"reference-count":96,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2007,10,1]],"date-time":"2007-10-01T00:00:00Z","timestamp":1191196800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Immunol"],"published-print":{"date-parts":[[2007,10]]},"DOI":"10.1038\/nri2161","type":"journal-article","created":{"date-parts":[[2007,9,3]],"date-time":"2007-09-03T09:55:16Z","timestamp":1188813316000},"page":"767-777","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":752,"title":["Unveiling the roles of autophagy in innate and adaptive immunity"],"prefix":"10.1038","volume":"7","author":[{"given":"Beth","family":"Levine","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vojo","family":"Deretic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","reference":[{"key":"BFnri2161_CR1","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1126\/science.290.5497.1717","volume":"290","author":"DJ Klionsky","year":"2000","unstructured":"Klionsky, D. J. & Emr, S. D. Autophagy as a regulated pathway of cellular degradation. Science 290, 1717\u20131721 (2000).","journal-title":"Science"},{"key":"BFnri2161_CR2","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1038\/nrm1660","volume":"6","author":"JJ Lum","year":"2005","unstructured":"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\u2013448 (2005).","journal-title":"Nature Rev. Mol. Cell. Biol."},{"key":"BFnri2161_CR3","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/S1534-5807(04)00099-1","volume":"6","author":"B Levine","year":"2004","unstructured":"Levine, B. & Klionsky, D. J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6, 463\u2013477 (2004).","journal-title":"Dev. Cell"},{"key":"BFnri2161_CR4","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1126\/science.1099993","volume":"306","author":"T Shintani","year":"2004","unstructured":"Shintani, T. & Klionsky, D. J. Autophagy in health and disease: a double-edged sword. Science 306, 990\u2013995 (2004). References 1\u20134 provide excellent general reviews on autophagy and its molecular mechanisms, physiological functions and roles in disease.","journal-title":"Science"},{"key":"BFnri2161_CR5","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.it.2005.08.003","volume":"26","author":"V Deretic","year":"2005","unstructured":"Deretic, V. Autophagy in innate and adaptive immunity. Trends. Immunol. 26, 523\u2013528 (2005).","journal-title":"Trends. Immunol."},{"key":"BFnri2161_CR6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00109-005-0014-4","volume":"84","author":"D Schmid","year":"2006","unstructured":"Schmid, D., Dengjel, J., Schoor, O., Stevanovic, S. & Munz, C. Autophagy in innate and adaptive immunity against intracellular pathogens. J. Mol. Med. 84, 1\u20139 (2006).","journal-title":"J. Mol. Med."},{"key":"BFnri2161_CR7","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.coi.2006.05.019","volume":"18","author":"V Deretic","year":"2006","unstructured":"Deretic, V. Autophagy as an immune defense mechanism. Curr. Opin. Immunol 18, 375\u2013382 (2006).","journal-title":"Curr. Opin. Immunol"},{"key":"BFnri2161_CR8","doi-asserted-by":"crossref","first-page":"2366","DOI":"10.1172\/JCI28796","volume":"116","author":"RM Andrade","year":"2006","unstructured":"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\u20132377 (2006).","journal-title":"J. Clin. Invest."},{"key":"BFnri2161_CR9","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1084\/jem.20061318","volume":"203","author":"YM Ling","year":"2006","unstructured":"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\u20132071 (2006). References 8\u20139 provide the first demonstrations that autophagy has a role in the elimination of parasites.","journal-title":"J. Exp. Med."},{"key":"BFnri2161_CR10","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1093\/jb\/mvj162","volume":"140","author":"A Amano","year":"2006","unstructured":"Amano, A., Nakagawa, I. & Yoshimori, T. Autophagy in innate immunity against intracellular bacteria. J. Biochem. 140, 161\u2013166 (2006).","journal-title":"J. Biochem."},{"key":"BFnri2161_CR11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.immuni.2007.01.005","volume":"26","author":"V Men\u00e9ndez-Benito","year":"2007","unstructured":"Men\u00e9ndez-Benito, V. & Neefjes, J. Autophagy in MHC class II presentation: sampling from within. Immunity 26, 1\u20133 (2007).","journal-title":"Immunity"},{"key":"BFnri2161_CR12","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1126\/science.1136880","volume":"315","author":"HK Lee","year":"2007","unstructured":"Lee, H. K., Lund, J. M., Ramanathan, B., Mizushima, N. & Iwasaki, A. Autophagy-dependent viral recognition by plasmacytoid dendritic cell. Science 315, 1398\u20131401 (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.","journal-title":"Science"},{"key":"BFnri2161_CR13","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1084\/jem.20061303","volume":"204","author":"HH Pua","year":"2007","unstructured":"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\u201331 (2007).","journal-title":"J. Exp. Med."},{"key":"BFnri2161_CR14","doi-asserted-by":"crossref","first-page":"5163","DOI":"10.4049\/jimmunol.177.8.5163","volume":"177","author":"C Li","year":"2006","unstructured":"Li, C. et al. Autophagy is induced in CD4+ T cells and important for the growth factor-withdrawal cell death. J. Immunol. 177, 5163\u20135168 (2006).","journal-title":"J. Immunol."},{"key":"BFnri2161_CR15","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1016\/j.cell.2006.12.044","volume":"128","author":"X Qu","year":"2007","unstructured":"Qu, X. et al. Autophagy gene-dependent clearance of apoptotic cells during embryonic development. Cell 128, 931\u2013946 (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.","journal-title":"Cell"},{"key":"BFnri2161_CR16","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1038\/ng1954","volume":"39","author":"J Hampe","year":"2007","unstructured":"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\u2013211 (2007).","journal-title":"Nature Genet."},{"key":"BFnri2161_CR17","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1038\/ng2032","volume":"39","author":"JD Rioux","year":"2007","unstructured":"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\u2013604 (2007).","journal-title":"Nature Genet."},{"key":"BFnri2161_CR18","doi-asserted-by":"crossref","first-page":"1665","DOI":"10.1053\/j.gastro.2007.03.034","volume":"132","author":"NJ Prescott","year":"2007","unstructured":"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\u20131671 (2007).","journal-title":"Gastroenterology"},{"key":"BFnri2161_CR19","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1038\/nature05911","volume":"447","author":"Wellcome The","year":"2007","unstructured":"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\u2013678 (2007).","journal-title":"Nature"},{"key":"BFnri2161_CR20","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1038\/ng2061","volume":"39","author":"M Parkes","year":"2007","unstructured":"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\u2013832 (2007). References 15\u201320 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.","journal-title":"Nature Genet."},{"key":"BFnri2161_CR21","doi-asserted-by":"crossref","first-page":"2445","DOI":"10.1016\/j.biocel.2004.02.002","volume":"36","author":"AJ Meijer","year":"2004","unstructured":"Meijer, A. J. & Codogno, P. Regulation and role of autophagy in mammalian cells. Int. J. Biochem. Cell. Biol. 36, 2445\u20132462 (2004).","journal-title":"Int. J. Biochem. Cell. Biol."},{"key":"BFnri2161_CR22","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1016\/j.mam.2006.08.002","volume":"27","author":"AJ Meijer","year":"2006","unstructured":"Meijer, A. J. & Codogno, P. Signalling and autophagy regulation in health and disease. Mol. Aspects. Med. 27, 411\u2013425 (2006). References 21\u201322 provide excellent, comprehensive reviews of the signalling pathways that regulate autophagy.","journal-title":"Mol. Aspects. Med."},{"key":"BFnri2161_CR23","doi-asserted-by":"crossref","first-page":"33076","DOI":"10.1074\/jbc.M507201200","volume":"280","author":"MP Byfield","year":"2005","unstructured":"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\u201333082 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR24","doi-asserted-by":"crossref","first-page":"14238","DOI":"10.1073\/pnas.0506925102","volume":"102","author":"T Nobukuni","year":"2005","unstructured":"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\u201314243 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2161_CR25","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1093\/embo-reports\/kve061","volume":"2","author":"A Kihara","year":"2001","unstructured":"Kihara, A., Kabeya, Y., Ohsumi, Y. & Yoshimori, T. Beclin\u2013phosphatidylinositol 3-kinase complex functions at the trans-Golgi network. EMBO Rep. 2, 330\u2013335 (2001).","journal-title":"EMBO Rep."},{"key":"BFnri2161_CR26","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1038\/ncb1426","volume":"8","author":"C Liang","year":"2006","unstructured":"Liang, C. et al. Autophagic and tumour suppressor activity of a novel Beclin 1-binding protein UVRAG. Nature Cell Biol. 8, 688\u2013699 (2006).","journal-title":"Nature Cell Biol."},{"key":"BFnri2161_CR27","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/nature05925","volume":"447","author":"GM Fimia","year":"2007","unstructured":"Fimia, G. M. et al. Ambra1 regulates autophagy and development of the nervous system. Nature 447, 1121\u20131125 (2007).","journal-title":"Nature"},{"key":"BFnri2161_CR28","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cell.2005.07.002","volume":"122","author":"S Pattingre","year":"2005","unstructured":"Pattingre, S. et al. Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122, 927\u2013939 (2005).","journal-title":"Cell"},{"key":"BFnri2161_CR29","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","volume":"124","author":"S Wullschleger","year":"2006","unstructured":"Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471\u2013484 (2006).","journal-title":"Cell"},{"key":"BFnri2161_CR30","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1073\/pnas.79.6.1889","volume":"79","author":"PO Seglen","year":"1982","unstructured":"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\u20131892 (1982).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2161_CR31","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S1534-5807(03)00296-X","volume":"5","author":"DJ Klionsky","year":"2003","unstructured":"Klionsky, D. J. et al. A unified nomenclature for yeast autophagy-related genes. Dev. Cell 5, 539\u2013545 (2003).","journal-title":"Dev. Cell"},{"key":"BFnri2161_CR32","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/35056522","volume":"2","author":"Y Ohsumi","year":"2001","unstructured":"Ohsumi, Y. Molecular dissection of autophagy: two ubiquitin-like systems. Nature Rev. Mol. Cell Biol. 2, 211\u2013216 (2001).","journal-title":"Nature Rev. Mol. Cell Biol."},{"issue":"Suppl. 2","key":"BFnri2161_CR33","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1038\/sj.cdd.4401765","volume":"12","author":"T Yorimitsu","year":"2005","unstructured":"Yorimitsu, T. & Klionsky, D. J. Autophagy: molecular machinery for self-eating. Cell Death Differ. 12 (Suppl. 2), 1542\u20131552 (2005).","journal-title":"Cell Death Differ."},{"key":"BFnri2161_CR34","doi-asserted-by":"crossref","first-page":"2156","DOI":"10.1016\/j.febslet.2007.01.096","volume":"581","author":"K Suzuki","year":"2007","unstructured":"Suzuki, K. & Ohsumi, Y. Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett. 581, 2156\u201361.(2007).","journal-title":"FEBS Lett."},{"key":"BFnri2161_CR35","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1083\/jcb.200507002","volume":"171","author":"G Bjorkoy","year":"2005","unstructured":"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\u2013614 (2005).","journal-title":"J. Cell. Biol."},{"key":"BFnri2161_CR36","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/ar.1092080302","volume":"208","author":"Y Rikihisa","year":"1984","unstructured":"Rikihisa, Y. Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae. Anat. Rec. 208, 319\u2013327 (1984).","journal-title":"Anat. Rec."},{"key":"BFnri2161_CR37","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/nrmicro865","volume":"2","author":"K Kirkegaard","year":"2004","unstructured":"Kirkegaard, K., Taylor, M. P. & Jackson, W. T. Cellular autophagy: surrender, avoidance and subversion by microorganisms. Nature Rev. Microbiol. 2, 301\u2013314 (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.","journal-title":"Nature Rev. Microbiol."},{"key":"BFnri2161_CR38","first-page":"159","volume":"120","author":"B Levine","year":"2005","unstructured":"Levine, B. Eating oneself and uninvited guests; autophagy-related pathways in cellular defense. Cell 120, 159\u2013162 (2005).","journal-title":"Cell"},{"key":"BFnri2161_CR39","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1083\/jcb.200106049","volume":"154","author":"RA Fratti","year":"2001","unstructured":"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\u2013644 (2001).","journal-title":"J. Cell. Biol."},{"key":"BFnri2161_CR40","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1034\/j.1600-0854.2003.00120.x","volume":"4","author":"I Vergne","year":"2003","unstructured":"Vergne, I., Chua, J. & Deretic, V. Mycobacterium tuberculosis phagosome maturation arrest: selective targeting of PI3P-dependent membrane trafficking. Traffic 4, 600\u2013606 (2003).","journal-title":"Traffic"},{"key":"BFnri2161_CR41","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1091\/mbc.e03-05-0307","volume":"15","author":"I Vergne","year":"2004","unstructured":"Vergne, I. et al. Mycobacterium tuberculosis phagosome maturation arrest: mycobacterial phosphatidylinositol analog phosphatidylinositol mannoside stimulates early endosomal fusion. Mol. Biol. Cell 15, 751\u2013760 (2004).","journal-title":"Mol. Biol. Cell"},{"key":"BFnri2161_CR42","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1016\/j.cell.2004.11.038","volume":"119","author":"MG Gutierrez","year":"2004","unstructured":"Gutierrez, M. G. et al. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119, 753\u2013766 (2004).","journal-title":"Cell"},{"key":"BFnri2161_CR43","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1126\/science.1106036","volume":"307","author":"M Ogawa","year":"2005","unstructured":"Ogawa, M. et al. Escape of intracellular Shigella from autophagy. Science 307, 727\u2013731 (2005).","journal-title":"Science"},{"key":"BFnri2161_CR44","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1126\/science.1103966","volume":"306","author":"I Nakagawa","year":"2004","unstructured":"Nakagawa, I. et al. Autophagy defends cells against invading group A Streptococcus. Science 306, 1037\u20131040 (2004). References 42\u201344 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).","journal-title":"Science"},{"key":"BFnri2161_CR45","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1126\/science.1129577","volume":"313","author":"SB Singh","year":"2006","unstructured":"Singh, S. B., Davis, A. S., Taylor, G. A. & Deretic, V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313, 1438\u20131441 (2006). This paper identified an important signalling mechanism (involving IRGM) that activates autophagy-dependent control of mycobacteria.","journal-title":"Science"},{"key":"BFnri2161_CR46","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1046\/j.1462-5822.2003.00292.x","volume":"5","author":"KA Rich","year":"2003","unstructured":"Rich, K. A., Burkett, C. & Webster, P. Cytoplasmic bacteria can be targets for autophagy. Cell. Microbiol. 5, 455\u2013468 (2003).","journal-title":"Cell. Microbiol."},{"key":"BFnri2161_CR47","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4161\/auto.3618","volume":"3","author":"BF Py","year":"2007","unstructured":"Py, B. F., Lipinski, M. M. & Yuan, J. Autophagy limits Listeria monocytogenes intracellular growth in the early phase of primary infection. Autophagy 3, 117\u2013125 (2007).","journal-title":"Autophagy"},{"key":"BFnri2161_CR48","doi-asserted-by":"crossref","first-page":"11374","DOI":"10.1074\/jbc.M509157200","volume":"281","author":"CL Birmingham","year":"2006","unstructured":"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\u201311383 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR49","doi-asserted-by":"crossref","first-page":"14578","DOI":"10.1073\/pnas.0601838103","volume":"103","author":"C Checroun","year":"2006","unstructured":"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\u201314583 (2006).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2161_CR50","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1083\/jcb.200510065","volume":"172","author":"A Yamamoto","year":"2006","unstructured":"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\u2013731 (2006).","journal-title":"J. Cell Biol."},{"key":"BFnri2161_CR51","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1462-5822.2005.00652.x","volume":"8","author":"M Ogawa","year":"2006","unstructured":"Ogawa, M. & Sasakawa, C. Intracellular survival of Shigella. Cell. Microbiol. 8, 177\u2013184 (2006).","journal-title":"Cell. Microbiol."},{"key":"BFnri2161_CR52","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1172\/JCI28792","volume":"117","author":"P Balachandran","year":"2007","unstructured":"Balachandran, P. et al. The ubiquitin ligase Cbl-b limits Pseudomonas aeruginosa exotoxin T-mediated virulence. J. Clin. Invest. 117, 419\u2013427 (2007).","journal-title":"J. Clin. Invest."},{"key":"BFnri2161_CR53","doi-asserted-by":"crossref","first-page":"30373","DOI":"10.1074\/jbc.M602097200","volume":"281","author":"M Djavaheri-Mergny","year":"2006","unstructured":"Djavaheri-Mergny, M. et al. NF-\u03baB activation represses tumor necrosis factor-\u03b1-induced autophagy. J. Biol. Chem. 281, 30373\u201330382 (2006).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR54","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1038\/sj.emboj.7601623","volume":"26","author":"R Scherz-Shouvai","year":"2007","unstructured":"Scherz-Shouvai, R. et al. Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J. 26, 1749\u20131760 (2007).","journal-title":"EMBO J."},{"key":"BFnri2161_CR55","doi-asserted-by":"crossref","first-page":"24","DOI":"10.4161\/auto.2176","volume":"2","author":"Z Talloczy","year":"2006","unstructured":"Talloczy, Z., Virgin, H. W. & Levine, B. PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2, 24\u201329 (2006).","journal-title":"Autophagy"},{"key":"BFnri2161_CR56","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1371\/journal.pbio.0030156","volume":"3","author":"WT Jackson","year":"2005","unstructured":"Jackson, W. T. et al. Subversion of cellular autophagosomal machinery by RNA viruses. PLoS Biol. 3, e156 (2005).","journal-title":"PLoS Biol."},{"key":"BFnri2161_CR57","doi-asserted-by":"crossref","first-page":"10136","DOI":"10.1074\/jbc.M306124200","volume":"279","author":"E Prentice","year":"2004","unstructured":"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\u201310141 (2004). References 56\u201357 indicate a role for components of the autophagic machinery in the establishment of viral replication complexes.","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR58","doi-asserted-by":"crossref","first-page":"e102","DOI":"10.1371\/journal.ppat.0020102","volume":"2","author":"S Cherry","year":"2006","unstructured":"Cherry, S. et al. COPI activity coupled with fatty acid biosynthesis is required for viral replication. PLoS Pathog. 2, e102 (2006).","journal-title":"PLoS Pathog."},{"key":"BFnri2161_CR59","doi-asserted-by":"crossref","first-page":"91","DOI":"10.4161\/auto.2.2.2297","volume":"2","author":"H Zhang","year":"2006","unstructured":"Zhang, H. et al. Cellular autophagy machinery is not required for vaccinia virus replication and maturation. Autophagy 2, 91\u201395 (2006).","journal-title":"Autophagy"},{"key":"BFnri2161_CR60","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.cell.2005.03.007","volume":"121","author":"Y Liu","year":"2005","unstructured":"Liu, Y. et al. Autophagy regulates programmed cell death during the plant innate immune response. Cell 121, 567\u2013577 (2005). This paper provided the first demonstration that loss-of-function mutations of autophagy genes increases susceptibility to microbial infection  in vivo.","journal-title":"Cell"},{"key":"BFnri2161_CR61","doi-asserted-by":"crossref","first-page":"8586","DOI":"10.1128\/JVI.72.11.8586-8596.1998","volume":"72","author":"XH Liang","year":"1998","unstructured":"Liang, X. H. et al. Protection against fatal Sindbis virus encephalitis by Beclin, a novel Bcl-2-interacting protein. J. Virol. 72, 8586\u20138596 (1998). This paper provided the first demonstration of an antimicrobial effect of an autophagy gene.","journal-title":"J. Virol."},{"key":"BFnri2161_CR62","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.chom.2006.12.001","volume":"1","author":"A Orvedahl","year":"2007","unstructured":"Orvedahl, A. et al. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1, 23\u201335 (2007). This paper provided the first evidence suggesting that autophagy inhibition is a mechanism by which viruses evade innate immunity and cause disease.","journal-title":"Cell Host Microbe"},{"key":"BFnri2161_CR63","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/352760880X.ch13","volume-title":"Autophagy in Immunity and Infection: a novel immune effector","author":"B Levine","year":"2006","unstructured":"Levine, B. in Autophagy in Immunity and Infection: a novel immune effector (ed. Deretic, V.) 227\u2013241 (Wiley-VCH Weinheim, Germany 2006)."},{"key":"BFnri2161_CR64","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/ni1303","volume":"7","author":"T Kawai","year":"2006","unstructured":"Kawai, T. & Akira, S. Innate immune recognition of viral infection. Nature Immunol. 7, 131\u2013137 (2006).","journal-title":"Nature Immunol."},{"key":"BFnri2161_CR65","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1084\/jem.20030162","volume":"198","author":"J Lund","year":"2003","unstructured":"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\u2013520 (2003).","journal-title":"J. Exp. Med."},{"key":"BFnri2161_CR66","doi-asserted-by":"crossref","first-page":"1506","DOI":"10.1002\/eji.1830270629","volume":"27","author":"MI Brazil","year":"1997","unstructured":"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\u20131514 (1997).","journal-title":"Eur. J. Immunol."},{"key":"BFnri2161_CR67","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.1002\/eji.200323730","volume":"33","author":"F Nimmerjahn","year":"2003","unstructured":"Nimmerjahn, F. et al. Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy. Eur. J. Immunol. 33, 1250\u20131259 (2003).","journal-title":"Eur. J. Immunol."},{"key":"BFnri2161_CR68","doi-asserted-by":"crossref","first-page":"3199","DOI":"10.1182\/blood-2004-09-3556","volume":"105","author":"D Dorfel","year":"2005","unstructured":"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\u20133205 (2005).","journal-title":"Blood"},{"key":"BFnri2161_CR69","doi-asserted-by":"crossref","first-page":"7922","DOI":"10.1073\/pnas.0501190102","volume":"102","author":"J Dengjel","year":"2005","unstructured":"Dengjel, J. et al. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc. Natl Acad. Sci. USA 102, 7922\u20137927 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2161_CR70","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1126\/science.1104904","volume":"307","author":"C Paludan","year":"2005","unstructured":"Paludan, C. et al. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307, 593\u2013596 (2005). This paper provided the first genetic evidence that autophagy components can be required for efficient MHC class II presentation of an endogenous antigen.","journal-title":"Science"},{"key":"BFnri2161_CR71","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1091\/mbc.e03-09-0704","volume":"15","author":"N Mizushima","year":"2004","unstructured":"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\u20131111 (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.","journal-title":"Mol. Biol. Cell"},{"key":"BFnri2161_CR72","doi-asserted-by":"crossref","first-page":"3746","DOI":"10.4049\/jimmunol.177.6.3746","volume":"177","author":"GS Taylor","year":"2006","unstructured":"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\u20133756 (2006).","journal-title":"J. Immunol."},{"key":"BFnri2161_CR73","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.immuni.2006.10.018","volume":"26","author":"D Schmid","year":"2007","unstructured":"Schmid, D., Pypaert, M. & Munz, C. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26, 79\u201392 (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.","journal-title":"Immunity"},{"key":"BFnri2161_CR74","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0070-2153(05)73007-6","volume":"73","author":"AC Massey","year":"2006","unstructured":"Massey, A. C., Zhang, C. & Cuervo, A. M. Chaperone-mediated autophagy in aging and disease. Curr. Top. Dev. Biol. 73, 205\u2013235 (2006).","journal-title":"Curr. Top. Dev. Biol."},{"key":"BFnri2161_CR75","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1023\/B:MCBI.0000041848.57020.57","volume":"263","author":"AM Cuervo","year":"2004","unstructured":"Cuervo, A. M. Autophagy: many paths to the same end. Mol. Cell. Biochem. 263, 55\u201372 (2004).","journal-title":"Mol. Cell. Biochem."},{"key":"BFnri2161_CR76","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.immuni.2005.03.009","volume":"22","author":"D Zhou","year":"2005","unstructured":"Zhou, D. et al. Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity 22, 571\u2013581 (2005).","journal-title":"Immunity"},{"key":"BFnri2161_CR77","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1073\/pnas.012485299","volume":"99","author":"Z Talloczy","year":"2002","unstructured":"Talloczy, Z. et al. Regulation of starvation- and virus-induced autophagy by the eIF2\u03b1 kinase signaling pathway. Proc. Natl Acad. Sci. USA 99, 190\u2013195 (2002). This paper demonstrated that the IFN-inducible, antiviral signalling molecule PKR is required for virus-induced autophagy.","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFnri2161_CR78","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1083\/jcb.200109094","volume":"157","author":"B Inbal","year":"2002","unstructured":"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\u2013468 (2002).","journal-title":"J. Cell. Biol."},{"key":"BFnri2161_CR79","doi-asserted-by":"crossref","first-page":"20722","DOI":"10.1074\/jbc.M413934200","volume":"280","author":"JO Pyo","year":"2005","unstructured":"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\u201320729 (2005).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR80","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1111\/j.1440-1711.2006.01454.x","volume":"84","author":"G Jia","year":"2006","unstructured":"Jia, G., Cheng, G., Gangahar, D. M. & Agrawal, D. K. Insulin-like growth factor-1 and TNF-\u03b1 regulate autophagy through c-jun N-terminal kinase and Akt pathways in human atherosclerotic vascular smooth cells. Immunol. Cell Biol. 84, 448\u2013454 (2006).","journal-title":"Immunol. Cell Biol."},{"key":"BFnri2161_CR81","doi-asserted-by":"crossref","first-page":"245","DOI":"10.4161\/auto.3717","volume":"3","author":"C Subauste","year":"2007","unstructured":"Subauste, C., Andrade, R. & Wessendarp, M. CD40\u2013TRAF6 and autophagy-dependent anti-microbial activity in macrophages. Autophagy 3, 245\u2013248 (2007).","journal-title":"Autophagy"},{"key":"BFnri2161_CR82","doi-asserted-by":"crossref","first-page":"12626","DOI":"10.1074\/jbc.272.19.12626","volume":"272","author":"K Wright","year":"1997","unstructured":"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\u201312633 (1997).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR83","doi-asserted-by":"crossref","first-page":"35243","DOI":"10.1074\/jbc.C100319200","volume":"276","author":"S Arico","year":"2001","unstructured":"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\u201335246 (2001).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR84","doi-asserted-by":"crossref","first-page":"992","DOI":"10.1074\/jbc.275.2.992","volume":"275","author":"A Petiot","year":"2000","unstructured":"Petiot, A., Ogier-Denis, E., Blommaart, E. F., Meijer, A. J. & Codogno, P. Distinct classes of phosphatidylinositol 3\u2032-kinases are involved in signaling pathways that control macroautophagy in HT-29 cells. J. Biol. Chem. 275, 992\u2013998 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFnri2161_CR85","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/S0163-7258(97)00165-4","volume":"78","author":"M Gale Jr","year":"1998","unstructured":"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\u201346 (1998).","journal-title":"Pharmacol. Ther."},{"key":"BFnri2161_CR86","unstructured":"Harris, J. et al. Autophagy is an effector of Th1\u2013Th2 polarization: Th2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. Immunity (in the press)."},{"key":"BFnri2161_CR87","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nri1270","volume":"4","author":"GA Taylor","year":"2004","unstructured":"Taylor, G. A., Feng, C. G. & Sher, A. p47 GTPases: regulators of immunity to intracellular pathogens. Nature Rev. Immunol. 4, 100\u2013109 (2004).","journal-title":"Nature Rev. Immunol."},{"key":"BFnri2161_CR88","doi-asserted-by":"crossref","first-page":"2679","DOI":"10.1172\/JCI26390","volume":"115","author":"B Levine","year":"2005","unstructured":"Levine, B. & Yuan, J. Autophagy in cell death: an innocent convict? J. Clin. Invest. 115, 2679\u20132688 (2005).","journal-title":"J. Clin. Invest."},{"key":"BFnri2161_CR89","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.cell.2007.02.023","volume":"128","author":"T Yoshimori","year":"2007","unstructured":"Yoshimori, T. Autophagy: paying Charon's toll. Cell 128, 833\u2013836 (2007).","journal-title":"Cell"},{"key":"BFnri2161_CR90","doi-asserted-by":"crossref","first-page":"2161","DOI":"10.1172\/JCI26185","volume":"116","author":"L Espert","year":"2006","unstructured":"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\u20132172 (2006).","journal-title":"J. Clin. Invest."},{"key":"BFnri2161_CR91","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.bbadis.2003.09.004","volume":"1639","author":"P Maderna","year":"2003","unstructured":"Maderna, P. & Godson, C. Phagocytosis of apoptotic cells and the resolution of inflammation. Biochim. Biophys. Acta 1639, 141\u2013151 (2003).","journal-title":"Biochim. Biophys. Acta"},{"key":"BFnri2161_CR92","doi-asserted-by":"crossref","first-page":"383","DOI":"10.3109\/s10165-005-0430-x","volume":"15","author":"GE Grossmayer","year":"2005","unstructured":"Grossmayer, G. E. et al. Removal of dying cells and systemic lupus erythematosus. Mod. Rheumatol. 15, 383\u2013390 (2005).","journal-title":"Mod. Rheumatol."},{"key":"BFnri2161_CR93","first-page":"161","volume":"305","author":"US Gaipl","year":"2006","unstructured":"Gaipl, U. S. et al. Inefficient clearance of dying cells and autoreactivity. Curr. Top. Microbiol. Immunol. 305, 161\u2013176 (2006).","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"BFnri2161_CR94","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1038\/ncpgasthep0528","volume":"3","author":"RS Sartor","year":"2006","unstructured":"Sartor, R. S. Mechanisms of disease pathogenesis: pathogenesis of Crohn's disease and ulcerative colitis. Nature Clin. Pract. Gastroenterol. Hepatol. 3, 390\u2013407 (2006).","journal-title":"Nature Clin. Pract. Gastroenterol. Hepatol."},{"key":"BFnri2161_CR95","doi-asserted-by":"crossref","first-page":"1627","DOI":"10.1016\/S0140-6736(07)60750-8","volume":"369","author":"DC Baumgart","year":"2007","unstructured":"Baumgart, D. C. & Carding, S. R. Inflammatory bowel disease: cause and immunobiology. Lancet 369, 1627\u20131640 (2007).","journal-title":"Lancet"},{"key":"BFnri2161_CR96","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.immuni.2007.05.022","volume":"27","author":"Y Xu","year":"2007","unstructured":"Xu, Y. et al. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27, 135\u2013144 (2007).","journal-title":"Immunity"}],"container-title":["Nature Reviews Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/nri2161.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nri2161","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/nri2161.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,10]],"date-time":"2025-04-10T13:09:48Z","timestamp":1744290588000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/nri2161"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,10]]},"references-count":96,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2007,10]]}},"alternative-id":["BFnri2161"],"URL":"https:\/\/doi.org\/10.1038\/nri2161","relation":{},"ISSN":["1474-1733","1474-1741"],"issn-type":[{"value":"1474-1733","type":"print"},{"value":"1474-1741","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,10]]},"assertion":[{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}