Skip to main content
SpringerLink
Log in

Autophagy and Immunity

  • Chapter
  • First Online:
Autophagy and Cancer

Part of the book series: Current Cancer Research ((CUCR,volume 8))

  • 1968 Accesses

Abstract

Autophagy is a highly conserved and regulated process in eukaryotic cells by which components of the cytoplasm, such as damaged organelles and foreign pathogens, become enveloped into double-membrane autophagosome vesicles that fuse with the lysosome for degradation. Autophagy has recently been implicated in modulation of both host innate and adaptive immune systems in response to infection. This chapter discusses how the autophagy pathway becomes activated upon bacterial or viral infection, the role of autophagy proteins in regulating innate immune signaling pathways, and the importance of autophagy in antigen presentation. Specifically, this chapter examines how pathogen-encoded virulence factors evade degradation by blocking the induction, nucleation, elongation, or maturation steps in the autophagy pathway. We also discuss how certain pathogens enhance autophagy induction or usurp autophagic machinery for their own replication. A comprehensive understanding of autophagic response to foreign pathogens may enable the discovery of novel antibiotic and antiviral drug targets.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Andrade RM, Wessendarp M, Gubbels MJ, Striepen B, Subauste CS (2006) CD40 induced macrophage anti-Toxoplasma gondii activity by triggering autophagy-dependent fusion of pathogen-­containing vacuoles and lysosomes. J Clin Invest 116(9):2366–2377

    PubMed  CAS  Google Scholar 

  • Barozzi P, Riva G, Vallerini D, Bosco R, Quadrelli C, Zanetti E, Potenza L, Forghieri F, Torelli G, Luppi M (2009) Indirect antitumor effects of mammalian target of rapamycin inhibitors against Kaposi sarcoma in transplant patients. Transplantation 88(4):597–598

    PubMed  Google Scholar 

  • Birmingham CL, Smith AC, Bakowski MA, Yoshimori T, Brumell JH (2006) Autophagy controls Salmonella infection in response to damage to the Salmonella-containing vacuole. J Biol Chem 281(16):11374–11383

    PubMed  CAS  Google Scholar 

  • Blanchet FP, Moris A, Nikolic DS, Lehmann M, Cardinaud S, Stalder R, Garcia E, Ninkins C, Leuba F, Wu L, Schwartz O, Deretic V, Piguet V (2010) Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune response. Immunity 32(5):654–669

    PubMed  CAS  Google Scholar 

  • Bryant P, Ploegh H (2004) Class II MHC peptide loading by the professionals. Curr Opin Immunol 16(1):96–102

    PubMed  CAS  Google Scholar 

  • Carpenter JE, Jackson W, Benetti L, Grose C (2011) Autophagosome formation during varicella-­zoster virus infection following endoplasmic reticulum stress and the unfolded protein response. J Virol 85(18):9414–9424

    PubMed  CAS  Google Scholar 

  • Cassady KA, Gross M (2002) The herpes simplex virus type 1 U(S)11 protein interacts with protein kinase R in infected cells and requires a 30-amino-acid sequence adjacent to a kinase substrate domain. J Virol 76(5):2029–2035

    PubMed  CAS  Google Scholar 

  • Cemma M, Kim PK, Brumell JH (2011) The ubiquitin-binding adaptor proteins p62/SQSTM1 and NDP52 are recruited independently to bacteria-associated microdomains to target Salmonella to the autophagy pathway. Autophagy 7(3):341–345

    PubMed  CAS  Google Scholar 

  • Chaumorcel M, Souquère S, Pierron G, Codogno P, Esclatine A (2008) Human cytomegalovirus controls a new autophagy-dependent antiviral defense mechanism. Autophagy 4(1):46–53

    PubMed  CAS  Google Scholar 

  • Chaumorcel M, Lussignol M, Mouna L, Cavignac Y, Fahie K, Cotte-Laffitte J, Geballe A, Brune W, Beau I, Codogno P, Esclatine A (2012) The human cytomegalovirus protein TRS1 inhibits autophagy via its interaction with beclin 1. J Virol 86(5):2571–2584

    PubMed  CAS  Google Scholar 

  • Checroun C, Wehrly TD, Fischer ER, Hayes SF, Celli J (2006) Autophagy-mediated reentry of Francisella tularensis into the endocytic compartments after cytoplasmic replication. Proc Natl Acad Sci USA 103(39):14578–14583

    PubMed  CAS  Google Scholar 

  • Chen N, Karantza V (2011) Autophagy as a therapeutic target in cancer. Cancer Biol Ther 11(2):157–168

    PubMed  Google Scholar 

  • Conney R, Baker J, Brain O, Danis B, Pichulik T, Allan P, Ferguson DJ, Campbell BJ, Jewell D, Simmons A (2010) NOD2 stimulation induces autophagy in dendritic cells influencing bacterial handling and antigen presentation. Nat Med 16(1):90–97

    Google Scholar 

  • Cuconati A, White E (2002) Viral homologs of BCL-2: role of apoptosis in the regulation of virus infection. Genes Dev 16(19):2465–2478

    PubMed  CAS  Google Scholar 

  • Davison AJ, Scott JE (1986) The complete DNA sequence of varicella-zoster virus. J Gen Virol 67(9):1759–1816

    PubMed  CAS  Google Scholar 

  • Delgado M, Elmaoued RA, Davis AS, Kyei G, Deretic V (2008) Toll-like receptors control autophagy. EMBO J 27(7):1110–1121

    PubMed  CAS  Google Scholar 

  • Dengjel J, Schoor O, Fischer R, Reich M, Kraus M, Müller M, Kreymborg K, Altenberend F, Brandenburg J, Kalbacher H, Brock R, Driessen C, Rammensee HG, Stevanovic S (2005) Autophagy promotes MHC class II presentation of peptides from intracellular source proteins. Proc Natl Acad Sci USA 102(22):7922–7927

    PubMed  CAS  Google Scholar 

  • Deretic V, Levine B (2009) Autophagy, immunity, and microbial adaptations. Cell Host Microbe 5(6):527–549

    PubMed  CAS  Google Scholar 

  • Dreux M, Gastaminza P, Wieland SF, Chisari FV (2009) The autophagy machinery is required to initiate hepatitis C virus replication. Proc Natl Acad Sci USA 106(33):14046–14051

    PubMed  CAS  Google Scholar 

  • English L, Chemali M, Duron J, Rondeau C, Laplante A, Gingras D, Alexander D, Leib D, Norbury C, Lippé R, Desjardins M (2009) Autophagy enhances the presentation of endogenous viral antigens on MHC class I molecules during HSV-1 infection. Nat Immunol 10(5):480–487

    PubMed  CAS  Google Scholar 

  • Espert L, Denizot M, Grimaldi M, Robert-Hebmann V, Gay B, Varbanov M, Codogno P, Biard-­Piechaczyk M (2006) Autophagy is involved in T cell death after binding of HIV-1 envelope proteins to CXCR4. J Clin Invest 116(8):2161–2172

    PubMed  CAS  Google Scholar 

  • Fernandez-Moreira E, Helbig JH, Swanson MS (2006) Membrane vesicles shed by Legionella pneumophila inhibit fusion of phagosomes with lysosomes. Infect Immun 74(6):3285–3295

    PubMed  CAS  Google Scholar 

  • Furuta N, Fujita N, Noda T, Yoshimori T, Amano A (2010) Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol Biol Cell 21(6):1001–1010

    PubMed  CAS  Google Scholar 

  • Gannagé M, Dormann D, Albrecht R, Dengjel J, Torossi T, Rämer PC, Lee M, Strowig T, Arrey F, Conenello G, Pypaert M, Andersen J, García-Sastre A, Münz C (2009) Matrix protein 2 of influenza A virus blocks autophagosome fusion with lysosomes. Cell Host Microbe 6(4):367–380

    PubMed  Google Scholar 

  • Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo ML, Deretic V (2004) Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 119(6):753–766

    PubMed  CAS  Google Scholar 

  • He B, Gross M, Roizman B (1997) The γ-34.5 protein of herpes simplex virus 1 complexes with protein phosphatase 1α to dephosphorylate the α subunit of the eukaryotic translation initiation factor 2 and preclude the shutoff of protein synthesis by double-stranded RNA-activated protein kinase. Proc Natl Acad Sci USA 94(3):843–848

    PubMed  CAS  Google Scholar 

  • Huang J, Canadien V, Lam GY, Steinberg BE, Dinauer MC, Magalhaes MA, Glogauer M, Grinstein S, Brumell JH (2009) Activation of antibacterial autophagy by NADPH oxidase. Proc Natl Acad Sci USA 106(15):6226–6231

    PubMed  CAS  Google Scholar 

  • Ingmundson A, Delprato A, Lambright DG, Roy CR (2007) Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 450(7168):365–369

    PubMed  CAS  Google Scholar 

  • Ishikawa H, Barber GN (2008) STING is an endoplasmic reticulum adaptor that facilitates innate immune signaling. Nature 455(7213):674–678

    PubMed  CAS  Google Scholar 

  • Jensen PE (2007) Recent advances in antigen processing and presentation. Nat Immunol 8(10):1041–1048

    PubMed  CAS  Google Scholar 

  • Joshi AD, Swanson MS (2011) Secrets of a successful pathogen: Legionella resistance to progression along the autophagic pathway. Front Microbiol 2:138

    PubMed  CAS  Google Scholar 

  • Joubert PE, Meiffren G, Grégoire IP, Pontini G, Richetta C, Flacher M, Azocar O, Vidalain PO, Vidal M, Lotteau V, Codogno P, Rabourdin-Combe C, Faure M (2009) Autophagy induction by the pathogen receptor CD46. Cell Host Microbe 6(4):354–366

    PubMed  Google Scholar 

  • Jounai N, Takeshita F, Kobiyama K, Sawano A, Miyawaki A, Xin KQ, Ishii KJ, Kawai T, Akira S, Suzuki K, Okuda K (2007) The Atg5-Atg12 conjugate associates with innate antiviral immune responses. Proc Natl Acad Sci USA 104(35):14050–14055

    PubMed  CAS  Google Scholar 

  • Kawai T, Takahashi K, Sato S, Coban C, Kumar H, Kato H, Ishii KJ, Takeuchi O, Akira S (2005) IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nat Immunol 6(10):981–988

    PubMed  CAS  Google Scholar 

  • Ke PY, Chen SS (2011) Activation of the unfolded protein response and autophagy after hepatitis C virus infection suppresses innate antiviral immunity in vitro. J Clin Invest 121(1):37–56

    PubMed  CAS  Google Scholar 

  • Khakpoor A, Panyasrivanit M, Wikan N, Smith DR (2009) A role for autophagolysosomes in dengue virus 3 production in HepG2 cells. J Gen Virol 90(5):1093–1103

    PubMed  CAS  Google Scholar 

  • Kim HJ, Lee S, Jung JU (2010) When autophagy meets viruses: a double-edge sword with functions in defense and offense. Semin Immunopathol 32(4):323–341

    PubMed  Google Scholar 

  • Ku B, Woo JS, Liang C, Lee KH, Hong HS, Xiaofei E, Kim KS, Jung JU, Oh BH (2008) Structural and biochemical basis for the inhibition of autophagy and apoptosis by viral BCL-2 of murine gamma-herpesvirus 68. PLoS Pathog 4(2):e25

    PubMed  Google Scholar 

  • Kudchodkar SB, Yu Y, Maguire TG, Alwine JC (2004) Human cytomegalovirus infection induces rapamycin-insensitive phosphorylation of downstream effectors of mTOR kinase. J Virol 78(20):11030–11039

    PubMed  CAS  Google Scholar 

  • Kumar D, Nath L, Kamal MA, Varshney A, Jain A, Singh S, Rao KV (2010) Genome-wide analysis of the host intracellular network that regulates survival of Mycobacterium tuberculosis. Cell 140(5):731–743

    PubMed  CAS  Google Scholar 

  • Kyei GB, Dinkins C, Davis AS, Roberts E, Singh SB, Dong C, Wu L, Kominami E, Ueno T, Yamamoto A, Federico M, Panganiban A, Vergne I, Deretic V (2009) Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186(2):255–268

    PubMed  CAS  Google Scholar 

  • Lauer GM, Walker BD (2001) Hepatitis C virus infection. N Engl J Med 345(1):41–52

    PubMed  CAS  Google Scholar 

  • Lee HK, Lund JM, Ramanathan B, Mizushima N, Iwasaki A (2007) Autophagy-dependent viral recognition by plasmacytoid dendritic cells. Science 315(5817):1398–1401

    PubMed  CAS  Google Scholar 

  • Lee JS, Li Q, Lee JY, Lee SH, Jeong JH, Lee HR, Chang H, Zhou FC, Gao SJ, Liang C, Jung JU (2009) FLIP-mediated autophagy regulation in cell death control. Nat Cell Biol 11(11):1355–1362

    PubMed  CAS  Google Scholar 

  • Lee HK, Mattei LM, Steinberg BE, Alberts P, Lee YH, Chervonsky A, Mizushima N, Grinstein S, Iwasaki A (2010) In vivo requirement for Atg5 in antigen presentation by dendritic cells. Immunity 32(2):227–239

    PubMed  CAS  Google Scholar 

  • Lei Y, Wen H, Yu Y, Taxman DJ, Zhang L, Widman DG, Swanson KV, Wen KW, Damania B, Moore CB, Giguère PM, Siderovski DP, Hiscott J, Razani B, Semenkovich CF, Chen X, Ting JPY (2012) The mitochondrial proteins NLRX1 and TUFM form a complex that regulates type I interferon and autophagy. Immunity 36(6):933–946

    PubMed  CAS  Google Scholar 

  • Leung CS, Haigh TA, Mackay LK, Rickinson AB, Taylor GS (2010) Nuclear location of an endogenously expressed antigen, EBNA1, restricts access to macroautophagy and the range of CD4 epitope display. Proc Natl Acad Sci USA 107(5):2165–2170

    PubMed  CAS  Google Scholar 

  • Levine B, Deretic V (2007) Unveiling the roles of autophagy in innate and adaptive immunity. Nat Rev Immunol 7(10):767–777

    PubMed  CAS  Google Scholar 

  • Matsunaga K, Saitoh T, Tabata K, Omori H, Satoh T, Kurotori N, Maejima I, Shirahama-Noda K, Ichimura T, Isobe T, Akira S, Noda T, Yoshimori T (2009) Two Beclin 1-binding proteins, Atg14L and Rubicon, reciprocally regulate autophagy at different stages. Nat Cell Biol 11(4):385–396

    PubMed  CAS  Google Scholar 

  • Meylan E, Curran J, Hofmann K, Moradpour D, Binder M, Bartenschlager R, Tschopp J (2005) Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437(7062):1167–1172

    PubMed  CAS  Google Scholar 

  • Mostowy S, Bonazzi M, Hamon MA, Tham TN, Mallet A, Lelek M, Gouin E, Demangel C, Brosch R, Zimmer C, Sartori A, Kinoshita M, Lecuit M, Cossart P (2010) Entrapment of intracytosolic bacteria by septin cage-like structures. Cell Host Microbe 8(5):433–444

    PubMed  CAS  Google Scholar 

  • Mostowy S, Sancho-Shimizu V, Hamon MA, Simeone R, Brosch R, Johansen T, Cossart P (2011) p62 and NDP52 proteins target intracytosolic Shigella and Listeria to different autophagy pathways. J Biol Chem 286(30):26987–26995

    PubMed  CAS  Google Scholar 

  • Münz C, Bickham KL, Subklewe M, Tsang ML, Chahroudi A, Kurilla MG, Zhang D, O’Donnell M, Steinman RM (2000) Human CD4(+) T lymphocytes consistently respond to the latent Epstein-Barr virus nuclear antigen EBNA1. J Exp Med 191(10):1649–1660

    PubMed  Google Scholar 

  • Nakagawa I, Amano A, Mizushima N, Yamamoto A, Yamaguchi H, Kamimoto T, Nara A, Funao J, Makata M, Tsuda K, Hamada S, Yoshimori T (2004) Autophagy defends cells against invading group A Streptococcus. Science 306(5698):1037–1040

    PubMed  CAS  Google Scholar 

  • Neefjes J, Jongsma ML, Paul P, Bakke O (2011) Towards a systems understanding of MHC class I and MHC class II antigen presentation. Nat Rev Immunol 11(12):823–836

    PubMed  CAS  Google Scholar 

  • Nichols LA, Adang LA, Kedes DH (2011) Rapamycin blocks production of KSHV/HHV8: insight into the anti-tumor activity of an immunosuppressant drug. PLoS One 6(1):e14535

    PubMed  CAS  Google Scholar 

  • Ogata M, Hino S, Saito A, Morikawa K, Kondo S, Kanemoto S, Murakami T, Taniguchi M, Tanii I, Yoshinaga K, Shiosaka S, Hammarback JA, Urano F, Imaizumi K (2006) Autophagy is activated for cell survival after endoplasmic reticulum stress. Mol Cell Biol 26(24):9220–9231

    PubMed  CAS  Google Scholar 

  • Ogawa M, Yoshimori T, Suzuki T, Sagara H, Mizushima N, Sasakawa C (2005) Escape of intracellular Shigella from autophagy. Science 307(5710):727–731

    PubMed  CAS  Google Scholar 

  • Orvedahl A, Alexander D, Talloczy Z, Sun Q, Wei Y, Zhang W, Burns D, Leib D, Levine B (2007) HSV-1 ICP34.5 confers neurovirulence by targeting the Beclin 1 autophagy protein. Cell Host Microbe 1(1):23–35

    PubMed  CAS  Google Scholar 

  • Paludan C, Schmid D, Landthaler M, Vockerodt M, Kube D, Tuschl T, Münz C (2005) Endogenous MHC class II processing of a viral nuclear antigen after autophagy. Science 207(5709):593–596

    Google Scholar 

  • Panyasrivanit M, Khakpoor A, Wikan N, Smith DR (2009) Co-localization of constituents of the dengue virus translation and replication machinery with amphisomes. J Gen Virol 90(2):448–456

    PubMed  CAS  Google Scholar 

  • Pattingre S, Tassa A, Qu X, Garuit R, Liang XH, Mizushima N, Packer M, Schneider MD, Levine B (2005) Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy. Cell 122(6):927–939

    PubMed  CAS  Google Scholar 

  • Perrin AJ, Jiang X, Birmingham CL, So NS, Brumell JH (2004) Recognition of bacteria in the cytosol of mammalian cells by the ubiquitin system. Curr Biol 14(9):806–811

    PubMed  CAS  Google Scholar 

  • Pilli M, Arko-Mensah J, Ponpuak M, Roberts E, Master S, Mandell MA, Dupont N, Ornatowski W, Jiang S, Bradfute SB, Bruun JA, Hansen TE, Johansen T, Deretic V (2012) TBK-1 promotes autophagosome-mediated antimicrobial defense by controlling autophagosome maturation. Immunity 37:223–234

    PubMed  CAS  Google Scholar 

  • Portillo JA, Okenka G, Reed E, Subauste A, Van Grol J, Gentil K, Komatsu M, Tanaka K, Landreth G, Levine B, Subauste CS (2010) The CD40-autophagy pathway is needed for host protection despite IFN-gamma-dependent immunity and CD40 induces autophagy via control of p21 levels. PLoS One 5(12):e14472

    PubMed  CAS  Google Scholar 

  • Ritthipichai K, Nan Y, Bossis I, Zhang Y (2012) Viral FLICE inhibitory protein of rhesus monkey rhadinovirus inhibits apoptosis by enhancing autophagosome formation. PLoS One 7(6):e39438

    PubMed  CAS  Google Scholar 

  • Saitoh T, Fujita N, Hayashi T, Takahara K, Satoh T, Lee H, Matsunaga K, Kageyama S, Omori H, Noda T, Yamamoto N, Kawai T, Ishii K, Takeuchi O, Yoshimori T, Akira S (2009) Atg9a controls dsDNA-driven dynamic translocation of STING and the innate immune response. Proc Natl Acad Sci USA 106(49):20842–20846

    PubMed  CAS  Google Scholar 

  • Scherz-Shouval R, Elazar Z (2011) Regulation of autophagy by ROS: physiology and pathology. Trends Biochem Sci 36(1):30–38

    PubMed  CAS  Google Scholar 

  • Schmid D, Pypaert M, Münz C (2007) Antigen-loading compartments for major histocompatibility complex class II molecules continuously receive input from autophagosomes. Immunity 26(1):79–92

    PubMed  CAS  Google Scholar 

  • Schröder M (2008) Endoplasmic reticulum stress responses. Cell Mol Life Sci 65(6):862–894

    PubMed  Google Scholar 

  • Seth RB, Sun L, Ea CK, Chen ZJ (2005) Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 122(5):669–682

    PubMed  CAS  Google Scholar 

  • Shi CS, Kehrl JH (2008) MyD88 and Trif target beclin 1 to trigger autophagy in macrophages. J Biol Chem 283(48):33175–33182

    PubMed  CAS  Google Scholar 

  • Shin DM, Jeon BY, Lee HM, Jin HS, Yuk JM, Song CH, Lee SH, Lee ZW, Cho SN, Kim JM, Friedman RL, Jo EK (2010) Mycobacterium tuberculosis Eis regulates autophagy, inflammation, and cell death through redox-dependent signaling. PLoS Pathog 6(12):e1001230

    PubMed  CAS  Google Scholar 

  • Shrivastava S, Raychoudhuri A, Steele R, Ray R, Ray RB (2011) Knockdown of autophagy enhances the innate immune response in hepatitis C virus-infected hepatocytes. Hepatology 53(2):406–414

    PubMed  CAS  Google Scholar 

  • Sin SH, Roy D, Wang L, Staudt MR, Fakhari FD, Patel DD, Henry D, Harrington WJ Jr, Damania BA, Dittmer DP (2007) Rapamycin is efficacious against primary effusion lymphoma (PEL) cell lines in vivo by inhibiting autocrine signaling. Blood 109(5):2165–2173

    PubMed  CAS  Google Scholar 

  • Singh SB, Davis AS, Taylor GA, Deretic V (2006) Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313(5792):438–441

    Google Scholar 

  • Sir D, Chen WL, Choi J, Wakita T, Yen TS, Ou JH (2008) Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response. Hepatology 48(4):1054–1061

    PubMed  CAS  Google Scholar 

  • Sir D, Tian Y, Chen WL, Ann DK, Yen TS, Ou JH (2010) The early autophagic pathway is activated by hepatitis B virus and required for viral DNA replication. Proc Natl Acad Sci USA 107(9):4383–4388

    PubMed  Google Scholar 

  • Sir D, Kuo CF, Tian Y, Liu HM, Huang EJ, Jung JU, Machida K, Ou JH (2012) Replication of hepatitis C virus RNA on autophagosomal membranes. J Biol Chem 287(22):18036–18043

    PubMed  CAS  Google Scholar 

  • Sodhi A, Montaner S, Patel V, Gómez-Román JJ, Li Y, Sausville EA, Sawai ET, Gutkind JS (2004) Akt plays a central role in sarcomagenesis induced by Kaposi’s sarcoma herpesvirus-encoded G protein coupled receptor. Proc Natl Acad Sci USA 101(14):4821–4826

    PubMed  CAS  Google Scholar 

  • Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, Ranieri E, Gesualdo L, Schena FP, Grandaliano G (2005) Sirolimus for Kaposi’s sarcoma in renal-transplant recipients. N Engl J Med 352(13):1317–1323

    PubMed  CAS  Google Scholar 

  • Takahashi MN, Jackson W, Laird DT, Culp TD, Grose C, Haynes JI II, Benetti L (2009) Varicella-­zoster virus infection induces autophagy in both cultured cells and human skin vesicles. J Virol 83(11):5466–5476

    PubMed  CAS  Google Scholar 

  • Takeda K, Akira S (2006) TLR signaling pathways. Semin Immunol 16(1):3–9

    Google Scholar 

  • Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A (2009) Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA 106(8):2770–2775

    PubMed  CAS  Google Scholar 

  • Tallóczy Z, Jiang W, Virgin HW IV, Leib DA, Scheuner D, Kaufman RJ, Eskelinen EL, Levine B (2002) Regulation of starvation- and virus-induced autophagy by the eIF2α kinase signaling pathway. Proc Natl Acad Sci USA 99(1):190–195

    PubMed  Google Scholar 

  • Tallóczy ZV, Virgin HW IV, Levine B (2006) PKR-dependent autophagic degradation of herpes simplex virus type 1. Autophagy 2(1):24–29

    PubMed  Google Scholar 

  • Tanida I, Fukasawa M, Ueno T, Kominami E, Wakita T, Hanada K (2009) Knockdown of autophagy-­related genes decreases the production of infectious hepatitis C virus particles. Autophagy 5(7):937–945

    PubMed  CAS  Google Scholar 

  • Thome M, Tschopp J (2001) Regulation of lymphocyte proliferation and death by FLIP. Nat Rev Immunol 1(1):50–58

    PubMed  CAS  Google Scholar 

  • Thurston TL, Ryzhakov G, Bloor S, von Muhlinen N, Randow F (2009) The TBK1 adaptor and autophagy receptor NDP52 restricts the proliferation of ubiquitin-coated bacteria. Nat Immunol 10(11):1215–1221

    PubMed  CAS  Google Scholar 

  • Tian Y, Sir D, Kuo CF, Ann DK, Ou JH (2011) Autophagy required for hepatitis B virus replication in transgenic mice. J Virol 85(24):13453–13456

    PubMed  CAS  Google Scholar 

  • Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, Magalhães JG, Yuan L, Soares F, Chea E, Le Bourhis L, Boneca IG, Allaoui A, Jones NL, Nuñez G, Girardin SE, Philpott DJ (2010) Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat Immunol 11(1):55–62

    PubMed  CAS  Google Scholar 

  • Vázquez CL, Colombo MI (2010) Coxiella burnetii modulates Beclin 1 and Bcl-2, preventing host cell apoptosis to generate a persistent bacterial infection. Cell Death Differ 17(3):421–438

    PubMed  Google Scholar 

  • Virgin HW, Levine B (2009) Autophagy genes in immunity. Nat Immunol 10(5):461–470

    PubMed  CAS  Google Scholar 

  • Watt KD, Dierkhising R, Heimbach JK, Charlton MR (2012) Impact of sirolimus and tacrolimus on mortality and graft loss in liver transplant recipients with or without hepatitis C virus: an analysis of the Scientific Registry of Transplant Recipients Database. Liver Transpl 18(9):1029–1036

    PubMed  Google Scholar 

  • Wei Y, Pattingre S, Sinha S, Bassik M, Levine B (2008) JNK1-mediated phosphorylation of Bcl-2 regulates starvation-induced autophagy. Mol Cell 30(6):678–688

    PubMed  CAS  Google Scholar 

  • White E (2012) Deconvoluting the context-dependent role for autophagy in cancer. Nat Rev Cancer 12(6):401–410

    PubMed  CAS  Google Scholar 

  • Williams BR (1999) PKR: a sentinel kinase for cellular stress. Oncogene 18(45):6112–6120

    PubMed  CAS  Google Scholar 

  • Xiaofei E, Hwang S, Oh S, Lee JS, Jeong JH, Gwack Y, Kowalik TF, Sun R, Jung JU, Liang C (2009) Viral Bcl-2-mediated evasion of autophagy aids chronic infection of gammaherpesvirus 68. PLoS Pathog 5(10):e1000609

    Google Scholar 

  • Xu LG, Wang YY, Han KJ, Li LY, Zhai Z, Shu HB (2005) VISA is an adapter protein required for virus-triggered IFN-beta signaling. Mol Cell 19(6):727–740

    PubMed  CAS  Google Scholar 

  • Xu Y, Jagannath C, Liu XD, Sharafkhaneh A, Kolodziejska KE, Eissa NT (2007) Toll-like receptor 4 is a sensor for autophagy associated with innate immunity. Immunity 27(1):135–144

    PubMed  CAS  Google Scholar 

  • Yang CS, Lee JS, Rodgers M, Min CK, Lee JY, Kim HJ, Kim CJ, Oh B, Zandi E, Yue Z, Kramnik I, Liang C, Jung JU (2012) Autophagy protein Rubicon mediates phagocytic NADPH oxidase activation in response to microbial infection or TLR stimulation. Cell Host Microbe 11(3):264–276

    PubMed  Google Scholar 

  • Yoshikawa Y, Ogawa M, Hain T, Yoshida M, Fukumatsu M, Kim M, Mimuro H, Nakagawa I, Yanagawa T, Ishii T, Kakizuka A, Sztul E, Chakraborty T, Sasakawa C (2009) Listeria monocytogenes ActA-mediated escape from autophagic recognition. Nat Cell Biol 11(10):1233–1240

    PubMed  CAS  Google Scholar 

  • Zheng YT, Shahnazari S, Brech A, Lamark T, Johansen T, Brumell JH (2009) The adaptor protein p62/SQSTM1 targets invading bacteria to the autophagy pathway. J Immunol 183(9):5909–5916

    PubMed  CAS  Google Scholar 

  • Zhong B, Yang Y, Li S, Wang YY, Li Y, Diao F, Lei C, He X, Zhang L, Tien P, Shu HB (2008) The adaptor protein MITA links virus-sensing receptors to IRF3 transcription factor activation. Immunity 29(4):538–550

    PubMed  CAS  Google Scholar 

  • Zhong Y, Wang QJ, Li X, Yan Y, Backer JM, Chait BT, Heintz N, Yue Z (2009) Distinct regulation of autophagic activity by Atg14L and Rubicon associated with Beclin 1-phosphatidylinositol-3-kinase complex. Nat Cell Biol 11(4):468–476

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Lindsey M. Silva & Jae U. Jung

Authors
  1. Lindsey M. Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jae U. Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lindsey M. Silva .

Editor information

Editors and Affiliations

  1. Penn State College of Medicine, Pharmacology, Penn State Hershey Cancer Institute, 500 University Drive, Hershey, 17033, Pennsylvania, USA

    Hong-Gang Wang

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Silva, L.M., Jung, J.U. (2013). Autophagy and Immunity. In: Wang, HG. (eds) Autophagy and Cancer. Current Cancer Research, vol 8. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6561-4_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-6561-4_8

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6560-7

  • Online ISBN: 978-1-4614-6561-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation