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Role of Macrophage Apoptosis in the Pathogenesis of Yersinia

  • Chapter
Role of Apoptosis in Infection

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 289))

Abstract

Yersinia species that are pathogenic for humans (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica) induce apoptosis in macrophages. Yersinia-induced apoptosis utilizes the mitochondrial pathway and is executed by activation of caspase cascades. The mechanism of Yersinia-induced apoptosis in macrophages has two essential components. One component is the innate immune response of macrophages to the pathogen, which leads to the activation of a survival response and a death response. Recognition of the bacterial cell envelope component lipopolysaccharide by Toll-like receptor 4 (TLR4) constitutes an important part of the innate immune response to the pathogen. The second essential component is YopJ, a protein secreted into Yersinia-infected macrophages via a bacterial type III secretion system, which selectively shuts down the survival pathway. In the absence of the survival pathway, the death pathway is executed, and Yersinia-infected macrophages undergo apoptosis. In this review, we introduce the basic features of Yersinia pathogenesis, summarize our current understanding of Yersinia-induced apoptosis, and discuss the role of apoptosis during Yersinia infection.

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References

  • Achtman M, Zurth K, Morelli G, Torrea G, Guiyoule A, Carniel E (1999) Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculo sis. Proc Natl Acad Sci USA 96:14043–14048

    Article  PubMed  Google Scholar 

  • Aepfelbacher M, Zumbihl R, Ruckdeschel K, Jacobi CA, Barz C, Heesemann J (1999) The tranquilizing injection of Yersinia proteins: a pathogen’s strategy to resist host defense. Biol Chem 380:795–802

    Article  PubMed  Google Scholar 

  • Autenrieth IB, Heesemann J (1993) In vivo neutralization of tumor necrosis factor alpha and interferon-gamma abrogates resistance to Yersinia enterocolitica in mice. Med Microbiol Immunol 181:333–338

    Google Scholar 

  • Autenrieth IB, Kempf V, Sprinz T, Preger S, Schnell A (1996) Defense mechanisms in Peyer’s patches and mesenteric lymph nodes against Yersinia enterocolitica involve integrins and cytokines. Infect Immun 64:1357–1368

    PubMed  Google Scholar 

  • Beuscher HU, Rodel F, Forsberg A, Rollinghoff M (1995) Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression. Infect Immun 63:1270–1277

    PubMed  Google Scholar 

  • Bliska JB (2000) Yop effectors of Yersinia spp. and actin rearrangements. Trends Microbiol 8:205–208

    Article  PubMed  Google Scholar 

  • Bohn E, Autenrieth IB (1996) IL-12 is essential for resistance against Yersinia enterocolitica by triggering IFN-gamma production in NK cells and CD4+ T cells. J Immunol 156:1458–1468

    PubMed  Google Scholar 

  • Boland A, Cornelis GR (1998) Role of YopP in suppression of tumor necrosis factor alpha release by macrophages during Yersinia infection. Infect Immun 66:1878–1884

    PubMed  Google Scholar 

  • Bottone EJ (1997) Yersinia enterocolitica: the charisma continues. Clin Microbiol Rev 10:257–276

    PubMed  Google Scholar 

  • Brubaker RR (1991) Factors promoting acute and chronic diseases caused by yersiniae. Clin Microbiol Rev 4:309–324

    PubMed  Google Scholar 

  • Brubaker RR (2003) Interleukin-10 and inhibition of innate immunity to Yersiniae: roles of Yops and LcrV (V antigen). Infect Immun 71:3673–3681

    Article  PubMed  Google Scholar 

  • Burdack S, Schmidt A, Knieschies E, Rollinghoff M, Beuscher HU (1997) Tumor necrosis factor-alpha expression induced by anti-YopB antibodies coincides with protection against Yersinia enterocolitica infection in mice. Med Microbiol Immunol (Berl) 185:223–229

    Article  Google Scholar 

  • Carniel E (1999) The Yersinia high-pathogenicity island. Int Microbiol 2:161–167

    PubMed  Google Scholar 

  • Carniel E (2002) Plasmids and pathogenicity islands of Yersinia. Curr Top Microbiol Immunol 264:89–108

    PubMed  Google Scholar 

  • Cavanaugh DC, Randall R (1959) The role of multiplication of Pasteurella pestis in mononuclear phagocytes in the pathogenesis of fleaborne plague. J Immunol 85:348–363

    Google Scholar 

  • Clark MA, Hirst BH, Jepson MA (1998) M-cell surface betal integrin expression and invasin-mediated targeting of Yersinia pseudotuberculosis to mouse Peyer’s patch M cells. Infect Immun 66:1237–1243

    PubMed  Google Scholar 

  • Cornelis GR (2002a) Yersinia type III secretion: send in the effectors. J Cell Biol 158:401–408

    Article  PubMed  Google Scholar 

  • Cornelis GR (2002b) The Yersinia Ysc-Yop ‘type III’ weaponry. Nat Rev Mol Cell Biol 3:742–752

    Article  PubMed  Google Scholar 

  • Denecker G, Declercq W, Geuijen CA, Boland A, Benabdillah R, van Gurp M, Sory MP, Vandenabeele P, Cornelis GR (2001) Yersinia enterocolitica YopP-induced apoptosis of macrophages involves the apoptotic signaling cascade upstream of bid. J Biol Chem 276:19706–19714

    Article  PubMed  Google Scholar 

  • Deveraux QL, Roy N, Stennicke HR, Van Arsdale T, Zhou Q, Srinivasula SM, Alnemri ES, Salvesen GS, Reed JC (1998) IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J 17:2215–2223

    Article  PubMed  Google Scholar 

  • El-Maraghi NRH, Mair NS (1979) The histopathology of enteric infection with Yersinia pseudotuberculosis. Am J Clin Pathol 71:631–639

    PubMed  Google Scholar 

  • Ghosh S, Karin M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109[Suppl]:S81–96

    Article  PubMed  Google Scholar 

  • Girardin SE, Boneca IG, Carneiro LA, Antignac A, Jehanno M, Viala J, Tedin K, Taha MK, Labigne A, Zahringer U, Coyle AJ, DiStefano PS, Bertin J, Sansonetti PJ, Philpott DJ (2003a) Nodl detects a unique muropeptide from gramnegative bacterial peptidoglycan. Science 300:1584–1587

    Article  PubMed  Google Scholar 

  • Girardin SE, Boneca IG, Viala J, Chamaillard M, Labigne A, Thomas G, Philpott DJ, Sansonetti PJ (2003b) Nod2 is a general sensor of peptidoglycan through muramyl dipeptide (MDP) detection. J Biol Chem 278:8869–8872

    Google Scholar 

  • Goguen JD, Walker WS, Hatch TP, Yother J (1986) Plasmid-determined cytotoxicity in Yersinia pestis and Yersinia pseudotuberculosis. Infect Immun 51:788–794

    PubMed  Google Scholar 

  • Grassl GA, Kracht M, Wiedemann A, Hoffmann E, Aepfelbacher M, von Eichel-Streiber C, Bohn E, Autenrieth IB (2003) Activation of NF-kappaB and IL-8 by Yersinia enterocolitica invasion protein is conferred by engagement of Racl and MAP kinase cascades. Cell Microbiol 5:957–971

    Article  PubMed  Google Scholar 

  • Haase R, Kirschning CJ, Sing A, Schrottner P, Fukase K, Kusumoto S, Wagner H, Heesemann J, Ruckdeschel K (2003) A dominant role of Toll-like receptor 4 in the signaling of apoptosis in bacteria-faced macrophages. J Immunol 171:4294–4303

    PubMed  Google Scholar 

  • Han KJ, Su X, Xu LG, Bin LH, Zhang J, Shu HB (2004) Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J Biol Chem 279:15652–15661

    Article  PubMed  Google Scholar 

  • Hanski C, Kutschka U, Schmoranzer HP, Naumann M, Stallmach A, Hahn H, Menge H (1989) Immunohistochemical and electron microscopic study of interaction of Yersinia enterocolitica serotype 08 with intestinal mucosa during experimental enteritis. Infect Immun 57:673–678

    PubMed  Google Scholar 

  • Hauser AR, Engel JN (1999) Pseudomonas aeruginosa induces type-III-secretion-mediated apoptosis of macrophages and epithelial cells. Infect Immun 67:5530–5537

    PubMed  Google Scholar 

  • Hoebe K, Du X, Georgel P, Janssen E, Tabeta K, Kim SO, Goode J, Lin P, Mann N, Mudd S, Crozat K, Sovath S, Han J, Beutler B (2003) Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 424:743–748

    PubMed  Google Scholar 

  • Hsu LC, Park JM, Zhang K, Luo JL, Maeda S, Kaufman RJ, Eckmann L, Guiney DG, Karin M (2004) The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428:341–345

    Article  PubMed  Google Scholar 

  • Inohara N, Ogura Y, Fontalba A, Gutierrez O, Pons F, Crespo J, Fukase K, Inamura S, Kusumoto S, Hashimoto M, Foster SJ, Moran AP, Fernandez-Luna JL, Nunez G (2003) Host recognition of bacterial muramyl dipeptide mediated through NOD2. Implications for Crohn’s disease. J Biol Chem 278:5509–5512

    PubMed  Google Scholar 

  • Irmler M, Thome M, Hahne M, Schneider P, Hofmann K, Steiner V, Bodmer JL, Schroter M, Burns K, Mattmann C, Rimoldi D, French LE, Tschopp J (1997) Inhibition of death receptor signals by cellular FLIP. Nature 388:190–195

    PubMed  Google Scholar 

  • Isberg RR, Van Nhieu GT (1995) The mechanism of phagocytic uptake promoted by invasin-integrin interaction. Trends Cell Biol 5:120–124

    Article  PubMed  Google Scholar 

  • Juris SJ, Shao F, Dixon JE (2002) Yersinia effectors target mammalian signalling pathways. Cell Microbiol 4:201–211

    Article  PubMed  Google Scholar 

  • Karahashi H, Amano F (1998) Apoptotic changes preceding necrosis in lipopolysaccharide-treated macrophages in the presence of cycloheximide. Exp Cell Res 241:373–383

    Article  PubMed  Google Scholar 

  • Karin M, Lin A (2002) NF-kappaB at the crossroads of life and death. Nat Immunol 3:221–227

    Article  PubMed  Google Scholar 

  • Lian CJ, Hwang WS, Kelly JK, Pai CH (1987a) Invasiveness of Yersinia enterocolitica lacking the virulence plasmid: an in vivo study. J Med Microbiol 24:219–226

    PubMed  Google Scholar 

  • Lian CJ, Hwang WS, Pai CH (1987b) Plasmid-mediated resistance to phagocytosis in Yersinia enterocolitica. Infect Immun 55:1176–1183

    PubMed  Google Scholar 

  • Marra A, Isberg RR (1997) Invasin-dependent and invasin-independent pathways for translocation of Yersinia pseudotuberculosis across the Peyer’s patch intestinal epithelium. Infect Immun 65:3412–3421

    PubMed  Google Scholar 

  • Mills SD, Boland A, Sory M-P, van der Smissen P, Kerbourch C, Finlay BB, Cornelis GR (1997) Yersinia enterocolitica induces apoptosis in macrophages by a process requiring functional type III secretion and translocation mechanisms and involving YopP, presumably acting as an effector protein. Proc Natl Acad Sci USA 94:12638–12643

    Article  PubMed  Google Scholar 

  • Monack DM, Mecsas J, Bouley D, Falkow S (1998) Yersinia-induced apoptosis in vivo aids in the establishment of a systemic infection. J Exp Med 188:2127–2137

    Article  PubMed  Google Scholar 

  • Monack DM, Mecsas J, Ghori N, Falkow S (1997) Yersinia signals macrophages to undergo apoptosis and YopJ is necessary for this cell death. Proc Natl Acad Sci USA 94:10385–10390

    Article  PubMed  Google Scholar 

  • Monack DM, Navarre WW, Falkow S (2001) Salmonella-induced macrophage death: the role of caspase-1 in death and inflammation. Microbes Infect 3:1201–1212

    Article  PubMed  Google Scholar 

  • Nakajima R, Brubaker RR (1993) Association between virulence of Yersinia pestis and suppression of gamma interferon and tumor necrosis factor alpha. Infect Immun 61:23–31

    PubMed  Google Scholar 

  • Navarre WW, Zychlinsky A (2000) Pathogen-induced apoptosis of macrophages: a common end for different pathogenic strategies. Cell Microbiol 2:265–273

    Article  PubMed  Google Scholar 

  • Orth K (2002) Function of the Yersinia effector YopJ. Curr Opin Microbiol 5:38–43

    Article  PubMed  Google Scholar 

  • Orth K, Palmer LE, Bao ZQ, Stewart S, Rudolph AE, Bliska JB, Dixon JE (1999) Inhibition of the mitogen-activated protein kinase superfamily by a Yersinia effector. Science 285:1920–1923

    Article  PubMed  Google Scholar 

  • Orth K, Xu Z, Mudgett MB, Bao ZQ, Palmer LE, Bliska JB, Mangel WF, Staskawicz B, Dixon JE (2000) Disruption of signaling by Yersinia effector YopJ, a ubiquitin-like protein protease. Science 290:1594–1597

    Article  PubMed  Google Scholar 

  • Palmer LE, Hobbie S, Galan JE, Bliska JB (1998) YopJ of Yersinia pseudotuberculosis is required for the inhibition of macrophage TNFα production and the downregulation of the MAP kinases p38 and JNK. Mol Microbiol 27:953–965

    Article  PubMed  Google Scholar 

  • Pepe J, Miller VL (1993) Yersinia enterocolitica invasion: a primary role in the initiation of infection. Proc Natl Acad Sci USA 90:6473–6477

    PubMed  Google Scholar 

  • Perry RD, Fetherston JD (1997) Yersinia pestis—etiologic agent of plague. Clin Microbiol Rev 10:35–66

    PubMed  Google Scholar 

  • Plano GV, Day JB, Ferracci F (2001) Type III export: new uses for an old pathway. Mol Microbiol 40:284–293

    Article  PubMed  Google Scholar 

  • Ramamurthi KS, Schneewind O (2002) Type III protein secretion in Yersinia species. Annu Rev Cell Dev Biol 18:107–133

    Article  PubMed  Google Scholar 

  • Revell PA, Miller VL (2001) Yersinia virulence: more than a plasmid. FEMS Microbiol Lett 205:159–64

    Article  PubMed  Google Scholar 

  • Ruckdeschel K, Harb S, Roggenkamp A, Hornef M, Zumbihl R, Kohler S, Heesemann J, Rouot B (1998) Yersinia enterocolitica impairs activation of transcription factor NF-KB: involvement in the induction of programmed cell death and in the suppression of the macrophage tumor necrosis factor a production. J Exp Med 187:1069–1079

    Article  PubMed  Google Scholar 

  • Ruckdeschel K, Machold J, Roggenkamp A, Schubert S, Pierre J, Zumbihl R, Liautard J-P, Heesemann J, Rouot B (1997a) Yersinia enterocolitica promotes deactivation of macrophage mitogen-activated protein kinases extracellular signal-regulated kinase-1/2, p38, and c-Jun NH2-terminal kinase. J Biol Chem 272:15920–15927

    Article  PubMed  Google Scholar 

  • Ruckdeschel K, Mannel O, Richter K, Jacobi CA, Trulzsch K, Rouot B, Heesemann J (2001a) Yersinia outer protein P of Yersinia enterocolitica simultaneously blocks the nuclear factor-kappa B pathway and exploits lipopolysaccharide signaling to trigger apoptosis in macrophages. J Immunol 166:1823–1831

    PubMed  Google Scholar 

  • Ruckdeschel K, Mannel O, Schrottner P (2002) Divergence of apoptosis-inducing and preventing signals in bacteria-faced macrophages through myeloid differentiation factor 88 and IL-1 receptor-associated kinase members. J Immunol 168:4601–4611

    PubMed  Google Scholar 

  • Ruckdeschel K, Richter K (2002) Lipopolysaccharide desensitization of macrophages provides protection against Yersinia enterocolitica-induced apoptosis. Infect Immun 70:5259–5264

    Article  PubMed  Google Scholar 

  • Ruckdeschel K, Richter K, Mannel O, Heesemann J (2001b) Arginine-143 of Yersinia enterocolitica YopP crucially determines isotype-related NF-kappaB suppression and apoptosis induction in macrophages. Infect Immun 69:7652–7662

    Article  PubMed  Google Scholar 

  • Ruckdeschel K, Roggenkamp A, Lafont V, Mangeat P, Heesemann J, Rouot B (1997b) Interaction of Yersinia enterocolitica with macrophages leads to macrophage cell death through apoptosis. Infect Immun 65:4813–4821

    PubMed  Google Scholar 

  • Schesser K, Spiik A-K, Dukuzumuremyi J-M, Neurath MF, Pettersson S, Wolf-Watz H (1998) The yopJ locus is required for Yersinia-mediated inhibition of NF-κB activation and cytokine expression: YopJ contains a eukaryotic SH2-like domain that is required for its repressive activity. Mol Microbiol 28:1067–1080

    Article  PubMed  Google Scholar 

  • Simonet M, Richard S, Berche P (1990) Electron microscopic evidence for in vivo extracellular localization of Yersinia pseudotuberculosis harboring the pYV plasmid. Infect Immun 58:841–845

    PubMed  Google Scholar 

  • Skurnik M, Peippo A, Ervela E (2000) Characterization of the O-antigen gene clusters of Yersinia pseudotuberculosis and the cryptic O-antigen gene cluster of Yersinia pestis shows that the plague bacillus is most closely related to and has evolved from Y pseudotuberculosis serotype 0:1b. Mol Microbiol 37:316–330

    Article  PubMed  Google Scholar 

  • Straley SC, Bowmer WS (1986) Virulence genes regulated at the transcriptional level by Ca2+ in Yersinia pestis include structural genes for outer membrane proteins. Infect Immun 51:445–454

    PubMed  Google Scholar 

  • Straley SC, Cibull ML (1989) Differential clearance and host-pathogen interactions of YopE− and YopK−YopL−Yersinia pestis in BALB/c mice. Infect Immun 57:1200–1210

    PubMed  Google Scholar 

  • Takeda K, Akira S (2004) Microbial recognition by Toll-like receptors. J Dermatol Sci 34:73–82

    Article  PubMed  Google Scholar 

  • Van Antwerp DJ, Martin SJ, Kafri T, Green DR, Verma IM (1996) Suppression of TNFα-induced apoptosis by NF-κB. Science 274:787–789

    Article  PubMed  Google Scholar 

  • Vazquez-Torres A, Fantuzzi G, Edwards CK 3rd, Dinarello CA, Fang FC (2001) Defective localization of the NADPH phagocyte oxidase to Salmonella-containing phagosomes in tumor necrosis factor p55 receptor-deficient macrophages. Proc Natl Acad Sci USA 98:2561–2565

    Article  PubMed  Google Scholar 

  • Viboud GI, Bliska JB (2001) A bacterial type III secretion system inhibits actin polymerization to prevent pore formation in host cell membranes. EMBO J 20:5373–5382

    Article  PubMed  Google Scholar 

  • Viboud GI, So SS, Ryndak MB, Bliska JB (2003) Proinflammatory signalling stimulated by the type III translocation factor YopB is counteracted by multiple effectors in epithelial cells infected with Yersinia pseudotuberculosis. Mol Microbiol 47:1305–1315

    Article  PubMed  Google Scholar 

  • Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351

    Article  PubMed  Google Scholar 

  • Wang C-U, Mayo MW, Baldwin AS Jr (1996) TNF-and cancer therapy-induced apoptosis: potentiation by inhibition of NF-cB. Science 274:784–787

    Article  PubMed  Google Scholar 

  • Zhang Y, Bliska JB (2003) Role of Toll-like receptor signaling in the apoptotic response of macrophages to Yersinia infection. Infect Immun 71:1513–1519

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Molecular Genetics and Microbiology, Center for Infectious Diseases, SUNY Stony Brook, Stony Brook, NY, 11794-5222, USA

    Y. Zhang & J. B. Bliska

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  1. Y. Zhang
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  2. J. B. Bliska
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Editors and Affiliations

  1. Bloomberg School of Public Health Department of Molecular Microbiology and Immunology, Johns Hopkins University, 615 N. Wolfe Street, Baltimore, MD, 21205, USA

    Diane E. Griffin MD, PhD

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Zhang, Y., Bliska, J.B. (2005). Role of Macrophage Apoptosis in the Pathogenesis of Yersinia. In: Griffin, D.E. (eds) Role of Apoptosis in Infection. Current Topics in Microbiology and Immunology, vol 289. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-27320-4_7

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