Browse > Article
http://dx.doi.org/10.4110/in.2013.13.1.1

Autophagy as an Innate Immune Modulator  

Oh, Ji Eun (Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))
Lee, Heung Kyu (Laboratory of Host Defenses, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST))
Publication Information
IMMUNE NETWORK / v.13, no.1, 2013 , pp. 1-9 More about this Journal
Abstract
Autophagy is a fundamental cellular process in eukaryotic cells for maintaining homeostasis by degrading cellular proteins and organelles. Recently, the roles of autophagy have been expanded to immune systems, which in turn modulate innate immune responses. More specifically, autophagy acts as a direct effector for protection against pathogens, as well as a modulator of pathogen recognition and downstream signaling in innate immune responses. In addition, autophagy controls autoimmunity and inflammatory disorders by negative regulation of immune signaling. In this review, we focus on recent advances in the role of autophagy in innate immune systems.
Keywords
Toll-like receptors; RIG-I-like receptors; NOD-like receptors;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 Klionsky, D. J. and S. D. Emr. 2000. Autophagy as a regulated pathway of cellular degradation. Science 290: 1717- 1721.   DOI
2 Mizushimam, N. and D. J. Klionsky. 2007. Protein turnover via autophagy: implications for metabolism. Annu. Rev. Nutr. 27: 19-40.   DOI
3 Massey, A. C., C. Zhang, and A. M. Cuervo. 2006. Chaperone- mediated autophagy in aging and disease. Curr. Top. Dev. Biol. 73: 205-235.   DOI
4 Cuervo, A. M. and J. H. Dice. 2000. Unique properties of lamp2a compared to other lamp2 isoforms. J. Cell Sci. 113 Pt24: 4441-4450.
5 Cuervo, A. M. and J. F. Dice. 1996. A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273: 501-503.   DOI
6 Chiang, H. L., S. R. Terlecky, C. P. Plant, and J. F. Dice. 1989. A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246: 382-385   DOI
7 Mizushima, N., Y. Ohsumi, and T. Yoshimori. 2002. Autophagosome formation in mammalian cells. Cell Struct. Funct. 27: 421-429.   DOI
8 Johansen, T. and T. Lamark. 2011. Selective autophagy mediated by autophagic adapter proteins Autophagy.7: 279-296.   DOI
9 Mizushima, N., T. Noda, T. Yoshimori, Y. Tanaka, T. Ishii, M. D. George, D. J. Klionsky, M. Ohsumi, and Y. Ohsumi. 1998. A protein conjugation system essential for autophagy. Nature 395: 395-398.   DOI
10 Ohsumi, Y. 2001. Molecular dissection of autophagy: two ubiquitin-like systems. Nat. Rev. Mol. Cell Biol. 2: 211-216.   DOI
11 Bjorkoy, G., T. Lamark, A. Brech, H. Outzen, M. Perander, A. Overvatn, H. Stenmark, and T. Johansen. 2005. p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J. Cell Biol. 171: 603-614.   DOI
12 Levine, B. and D. J. Klionsky. 2004. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 6: 463-477.   DOI
13 Levine, B. and G. Kroemer. 2008. Autophagy in the pathogenesis of disease. Cell 132: 27-42.   DOI
14 Shintani, T. and D. J. Klionsky. 2004. Autophagy in health and disease: a double-edged sword. Science 306: 990-995.   DOI
15 Nakagawa, I., A. Amano, N. Mizushima, A. Yamamoto, H. Yamaguchi, T. Kamimoto, A. Nara, J. Funao, M. Nakata, K. Tsuda, S. Hamada, and T. Yoshimori. 2004. Autophagy defends cells against invading group A Streptococcus. Science 306: 1037-1040.   DOI
16 Gutierrez, M. G., S. S. Master, S. B. Singh, G. A. Taylor, M. I. Colombo, and V. Deretic. 2004. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119: 753-766.   DOI
17 Xu, Y., C. Jagannath, X. D. Liu, A. Sharafkhaneh, K. E. Kolodziejska, and N. T. Eissa. 2007. Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27: 135-144.   DOI
18 Delgado, M. A., R. A. Elmaoued, A. S. Davis, G. Kyei, and V. Deretic. 2008. Toll-like receptors control autophagy. EMBO J. 27: 1110-1121.   DOI
19 Sanjuan, M. A., C. P. Dillon, S. W. Tait, S. Moshiach, F. Dorsey, S. Connell, M. Komatsu, K. Tanaka, J. L. Cleveland, S. Withoff, and D. R. Green. 2007. Toll-like receptor signalling in macrophages links the autophagy pathway to phago cytosis. Nature 450: 1253-1257.   DOI
20 Saitoh, T., N. Fujita, M. H. Jang, S. Uematsu, B. G. Yang, T. Satoh, H. Omori, T. Noda, N. Yamamoto, M. Komatsu, K. Tanaka, T. Kawai, T. Tsujimura, O. Takeuchi, T. Yoshimori, and S. Akira. 2008. Loss of the autophagy protein Atg16L1 enhances endotoxin-induced IL-1beta production. Nature 456: 264-268.   DOI
21 Dengjel, J., O. Schoor, R. Fischer, M. Reich, M. Kraus, M. Muller, K. Kreymborg, F. Altenberend, J. Brandenburg, H. Kalbacher, R. Brock, C. Driessen, H. G. Rammensee, and S. Stevanovic. 2005. Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc. Natl. Acad. Sci. U. S. A. 102: 7922-7927.   DOI
22 Pua, H. H. and Y. W. He. 2007. Maintaining T lymphocyte homeostasis: another duty of autophagy. Autophagy 3: 266-267   DOI
23 Paludan, C., D. Schmid, M. Landthaler, M. Vockerodt, D. Kube, T. Tuschl, and C. Münz. 2005. Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 307: 593-596.   DOI
24 Schmid, D., M. Pypaert, and C. Münz. 2007. Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26: 79-92.   DOI
25 Pua, H. H., I. Dzhagalov, M. Chuck, N. Mizushima, and Y. W. He. 2007. A critical role for the autophagy gene Atg5 in T cell survival and proliferation. J. Exp. Med. 204: 25-31.   DOI
26 Miller, B. C., Z. Zhao, L. M. Stephenson, K. Cadwell, H. H. Pua, H. K. Lee, N. N. Mizushima, A. Iwasaki, Y. W. He, W. Swat, H. W. Virgin, 4th. 2008. The autophagy gene ATG5 plays an essential role in B lymphocyte development. Autophagy 4: 309-314.   DOI
27 Schmid, D. and C. Münz. 2007. Innate and adaptive immunity through autophagy. Immunity 27: 11-21.   DOI
28 Yuk, J. M., D. M. Shin, H. M. Lee, C. S. Yang, H. S. Jin, K. K. Kim, Z. W. Lee, S. H. Lee, J. M. Kim, and E. K. Jo. 2009. Vitamin D3 induces autophagy in human monocytes/ macrophages via cathelicidin. Cell Host Microbe 6: 231-243.   DOI
29 Watson, R. O., P. S. Manzanillo, and J. S. Cox. 2012. Extracellular M. tuberculosis DNA targets bacteria for autophagy by activating the host DNA-sensing pathway. Cell 150: 803-815.   DOI
30 Mahairas, G. G., P. J. Sabo, M. J. Hickey, D. C. Singh, and C. K. Stover. 1996. Molecular analysis of genetic differences between Mycobacterium bovis BCG and virulent M. bovis. J. Bacteriol. 178: 1274-1282.   DOI
31 Pym, A. S., P. Brodin, L. Majlessi, R. Brosch, C. Demangel, A. Williams, K. E. Griffiths, G. Marchal, C. Leclerc, and S. T. Cole. 2003. Recombinant BCG exporting ESAT-6 confers enhanced protection against tuberculosis. Nat. Med. 9: 533-   DOI
32 Thurston, T. L., G. Ryzhakov, S. Bloor, N. von Muhlinen, and F. Randow. 2009. The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat. Immunol. 10: 1215-1221.   DOI
33 Smith, J., J. Manoranjan, M. Pan, A. Bohsali, J. Xu, J. Liu, K. L. McDonald, A. Szyk, N. LaRonde-LeBlanc, and L. Y. Gao. 2008. Evidence for pore formation in host cell membranes by ESX-1-secreted ESAT-6 and its role in Mycobacterium marinum escape from the vacuole. Infect. Immun. 76: 5478-5487.   DOI
34 Rich, K. A., C. Burkett, and P. Webster. 2003. Cytoplasmic bacteria can be targets for autophagy. Cell. Microbiol. 5: 455-468.   DOI
35 Zheng, Y. T., S. Shahnazari, A. Brech, T. Lamark, T. Johansen, and J. H. Brumell. 2009. The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J. Immunol. 183: 5909-5916.   DOI
36 Yuk, J. M., T. Yoshimori, and E. K. Jo. 2012. Autophagy and bacterial infectious diseases. Exp. Mol. Med. 44: 99-108.   DOI
37 Iwasaki, A. and R. Medzhitov. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987-995.   DOI
38 Oh, J. E. and H. K. Lee. 2012. Modulation of pathogen recognition by autophagy. Front Immunol. 3: 44.
39 Lee, M. S. and Y. J. Kim. 2007. Signaling pathways downstream of pattern-recognition receptors and their cross talk. Annu. Rev. Biochem. 76: 447-480.   DOI
40 Cooney, R., J. Baker, O. Brain, B. Danis, T. Pichulik, P. Allan, D. J. Ferguson, B. J. Campbell, D. Jewell, and A. Simmons. 2010. NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat. Med. 16: 90-97.   DOI
41 Travassos, L. H., L. A. Carneiro, M. Ramjeet, S. Hussey, Y. G. Kim, J. G. Magalhaes, L. Yuan, F. Soares, E. Chea, L. Le Bourhis, I. G. Boneca, A. Allaoui, N. L. Jones, G. Nunez, S. E. Girardin, and D. J. Philpott. 2010. Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11: 55-62.   DOI
42 Liang, X. H., L. K. Kleeman, H. H. Jiang, G. Gordon, J. E. Goldman, G. Berry, B. Herman, and B. Levine. 1998. Protection against fatal Sindbis virus encephalitis by beclin, a novel Bcl-2-interacting protein. J. Virol. 72: 8586-8596.
43 Cho, J. H. and C. T. Weaver. 2007. The genetics of inflammatory bowel disease. Gastroenterology 133: 1327-1339.   DOI
44 Hampe, J., A. Franke, P. Rosenstiel, A. Till, M. Teuber, K. Huse, M. Albrecht, G. Mayr, F. M. De La Vega, J. Briggs, S. Gunther, N. J. Prescott, C. M. Onnie, R. Hasler, B. Sipos, U. R. Folsch, T. Lengauer, M. Platzer, C. G. Mathew, M. Krawczak, and S. Schreiber. 2007. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat. Genet. 39: 207-211   DOI
45 Rioux, J. D., R. J. Xavier, K. D. Taylor, M. S. Silverberg, P. Goyette, A. Huett, T. Green, P. Kuballa, M. M. Barmada, L. W. Datta, Y. Y. Shugart, A. M. Griffiths, S. R. Targan, A. F. Ippoliti, E. J. Bernard, L. Mei, D. L. Nicolae, M. Regueiro, L. P. Schumm, A. H. Steinhart, J. I. Rotter, R. H. Duerr, J. H. Cho, M. J. Daly, and S. R. Brant. 2007. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat. Genet. 39: 596-604.   DOI
46 Orvedahl, A., S. MacPherson, R. Sumpter, Jr, Z. Tallóczy, Z. Zou, and B. Levine. 2010. Autophagy protects against Sindbis virus infection of the central nervous system. Cell Host Microbe 7: 115-127.   DOI
47 Orvedahl, A., D. Alexander, Z. Tallóczy, Q. Sun, Y. Wei, W. Zhang, D. Burns, D. A. Leib, and B. Levine. 2007. HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1: 23-35.   DOI
48 Alexander, D. E. and D. A. Leib. 2008. Xenophagy in herpes simplex virus replication and pathogenesis. Autophagy 4: 101-103.   DOI
49 Barton, G. M. 2007. Viral recognition by Toll-like receptors. Semin. Immunol. 19: 33-40.   DOI
50 Lee, H. K. and A. Iwasaki. 2008. Autophagy and antiviral immunity. Curr. Opin. Immunol. 20: 23-29.   DOI
51 Tal, M. C. and A. Iwasaki. 2009. Autophagy and innate recognition systems. Curr. Top. Microbiol. Immunol. 335: 107-121
52 Foy, E., K. Li, R. Sumpter, Jr, Y. M. Loo, C. L. Johnson, C. Wang, P. M. Fish, M. Yoneyama, T. Fujita, S. M. Lemon, M. Gale, Jr. 2005. Control of antiviral defenses through hepatitis C virus disruption of retinoic acid-inducible gene-I signaling. Proc. Natl. Acad. Sci. U. S. A. 102: 2986-2991.   DOI
53 Yordy, B. and A. Iwasaki. 2011. Autophagy in the control and pathogenesis of viral infection. Curr. Opin. Virol. 1: 196-203.   DOI
54 Yoneyama, M., M. Kikuchi, T. Natsukawa, N. Shinobu, T. Imaizumi, M. Miyagishi, K. Taira, S. Akira, and T. Fujita. 2004. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 5: 730-737.   DOI
55 Yoneyama, M., M. Kikuchi, K. Matsumoto, T. Imaizumi, M. Miyagishi, K. Taira, E. Foy, Y. M. Loo, M. Gale, Jr, S. Akira, S. Yonehara, A. Kato, and T. Fujita. 2005. Shared and unique functions of the DExD/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity. J. Immunol. 175: 2851- 2858.   DOI
56 Jounai, N., F. Takeshita, K. Kobiyama, A. Sawano, A. Miyawaki, K. Q. Xin, K. J. Ishii, T. Kawai, S. Akira, K. Suzuki, and K. Okuda. 2007. The Atg5 Atg12 conjugate associates with innate antiviral immune responses. Proc. Natl. Acad. Sci. U. S. A. 104: 14050-14055.   DOI
57 Tal, M. C., M. Sasai, H. K. Lee, B. Yordy, G. S. Shadel, and A. Iwasaki. 2009. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc. Natl. Acad. Sci. U. S. A. 106: 2770-2775.   DOI
58 Schroder, K. and J. Tschopp. 2010. The inflammasomes. Cell 140: 821-832.   DOI
59 Shi, C. S., K. Shenderov, N. N. Huang, J. Kabat, M. Abu-Asab, K. A. Fitzgerald, A. Sher, and J. H. Kehrl. 2012. Activation of autophagy by inflammatory signals limits IL-1$\beta$ production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol. 13: 255-263.   DOI
60 Bodemann, B. O., A. Orvedahl, T. Cheng, R. R. Ram, Y. H. Ou, E. Formstecher, M. Maiti, C. C. Hazelett, E. M. Wauson, M. Balakireva, J. H. Camonis, C. Yeaman, B. Levine, and M. A. White. 2011. RalB and the exocyst mediate the cellular starvation response by direct activation of autophagosome assembly. Cell 144: 253-267.   DOI