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Legionella pneumophila Invasion of Mononuclear Phagocytes

  • Chapter
Bacterial Invasiveness

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 209))

Abstract

Legionella pneumophila is a gram-negative bacterium that causes legionnaires’ disease. This organism is widespread in fresh water and is typically found growing in association with protozoans and blue-green algae. In human beings, L pneumophila infects alveolar macrophages, wherein the organism survives and replicates within a specialized phagosome or vacuole (the Legionella-specialized phagosome, LSP). The interaction between L. pneumophila and human mononuclear phagocytes has been studied in considerable detail, and it provides an interesting and informative example of how one organism successfully achieves intracellular parasitism.

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References

  • Armstrong JA, Hart PD (1971) Response of cultured macrophages to Mycobacterium tuberculosis with observations on fusion of lysosomes with phagosomes. J Exp Med 134:713–740

    Article  PubMed  CAS  Google Scholar 

  • Bellinger-Kawahara C, Horwitz MA (1990) Complement component C3 fixes selectively to the major outer membrane protein (MOMP) of Legionella pneumophila and mediates phagocytosis of liposome-MOMP complexes by human monocytes. J Exp Med 172:1201–1210

    Article  PubMed  CAS  Google Scholar 

  • Berger KH, Isberg RR (1993) Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol 7:7–19

    Article  PubMed  CAS  Google Scholar 

  • Berger KH, Merriam JJ, Isberg RR (1994) Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol Microbiol 14:809–822

    Article  PubMed  CAS  Google Scholar 

  • Bermudez LE, Young LS, Enkel H (1991) Interaction of Mycobacterium avium complex with human macrophages:roles of membrane receptors and serum proteins. Infect Immun 59:1697–1702

    PubMed  CAS  Google Scholar 

  • Blackwell JM, Ezekowitz RAB, Roberts MB, Channon JY, Sim RB, Gordon S (1985) Macrophage complement and lectin-like receptors bind Leishmania in the absence of serum. J Exp Med 162:324–331

    Article  PubMed  CAS  Google Scholar 

  • Blander SJ, Horwitz MA (1989) Vaccination with the major secretory protein of Legionella pneumophila induces cell-mediated and protective immunity in a guinea pig model of legionnaires’ disease. J Exp Med 169:691–705

    Article  PubMed  CAS  Google Scholar 

  • Blander SJ, Breiman RF, Horwitz MA (1989) A live avirulent mutant Legionella pneumophila vaccine induces protective immunity against lethal aerosol challenge. J Clin Invest 83:810–815

    Article  PubMed  CAS  Google Scholar 

  • Blander SJ, Szeto L, Shuman HA, Horwitz MA (1990) An immuno-protective molecule, the major secretory protein of Legionella pneumophila, is not a virulence factor in a guinea pig model of legionnaires’ disease. J Clin Invest 86:817–824

    Article  PubMed  CAS  Google Scholar 

  • Brand BC, Sadosky AB, Shuman HA (1994) Molecular genetic analysis of the icm region in Legionella pneumophila. Mol Microbiol 14:797–808

    Article  PubMed  CAS  Google Scholar 

  • Bullock WE, Wright SD (1987) Role of the adherence-promoting receptors, CR3, LFA-1, and p150, 95 in binding of Histoplasma capsulatum by human macrophages. J Exp Med 165:195–210

    Article  PubMed  CAS  Google Scholar 

  • Byrd TF, Horwitz MA (1989) Interferon gamma-activated human monocytes down-regulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J Clin Invest 83:1457–1465

    Article  PubMed  CAS  Google Scholar 

  • Byrd TF, Horwitz MA (1991a) Chloroquine inhibits the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. A potential new mechanism for the therapeutic effect of chloroquine against intracellular pathogens. J Clin Invest 88:351–357

    CAS  Google Scholar 

  • Byrd TF, Horwitz MA (1991b) Lactoferrin inhibits or promotes Legionella pneumophila intracellular multiplication in nonactivated and interferon gamma-activated human monocytes depending upon its degree of iron saturation. Iron-lactoferrin and nonphysiologic iron chelates reverse monocyte activation against Legionella pneumophila. J Clin Invest 88:1103–1112

    CAS  Google Scholar 

  • Byrd TF, Horwitz MA (1993) Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes:coordinate upregulation by iron-transferrin and down-regulation by interferon gamma. J Clin Invest 91:969–976

    Article  PubMed  CAS  Google Scholar 

  • Catrenich CE, Johnson W (1989) Characterization of the selective inhibition of growth of virulent Legionella pneumophila by supplemented Mueller-Hinton medium. Infect Immun 57:1862–1864

    PubMed  CAS  Google Scholar 

  • Chang KP (1979) Leishmania donovani promastigote-macrophage surface interactions in vitro. Exp Parasitol 48:175–189

    Article  PubMed  CAS  Google Scholar 

  • Cianciotto NP, Einstein Bl, Mody CH, Toews GB, Engelberg NC (1989) A Legionella pneumophila gene encoding a species-specific surface protein potentiates initiation of intracellular infection. Infect Immun 57:1225–1262

    Google Scholar 

  • Cianciotto NP, Einstein Bl, Mody CH, Engelberg NC (1990) A mutation in the mip gene results in attenuation of Legionella pneumophila virulence. J Infect Dis 162:121–126

    Article  PubMed  CAS  Google Scholar 

  • Clemens DL, Horwitz MA (1992) Membrane sorting during phagocytosis:selective exclusion of MHC molecules but not complement receptor CR3 during conventional and coiling phagocytosis. J Exp Med 175:1317–1326

    Article  PubMed  CAS  Google Scholar 

  • Clemens, DL, Horwitz MA (1993) Hypoexpression of major histocompatibility complex molecules on Legionella pneumophila phagosomes and phagolysosomes. Infect Immun 61:2803–2812

    PubMed  CAS  Google Scholar 

  • Clemens DL, Horwitz MA (1995) Characterization of the Mycobacterium tuberculosis phagosome and evidence that phagosomal maturation is inhibited. J Exp Med 181:257–270

    Article  PubMed  CAS  Google Scholar 

  • Crowle A, Dahl R, Ross E, May M (1991) Evidence that vesicles containing living virulent M. tuberculosis or M. avium in cultured human macrophages are not acidic. Infect Immun 59:1823–1831

    PubMed  CAS  Google Scholar 

  • Drevets DA, Campbell PA (1991) Roles of complement and complement receptor type 3 in phagocytosis of Listeria monocytogenes by inflammatory mouse peritoneal macrophages. Infect Immun 59:2645–2652

    PubMed  CAS  Google Scholar 

  • Engelberg NC, Pearlman E, Einstein Bl (1984) Legionella pneumophla surface antigens cloned and expressed in E. coli are translocated to the host cell surface and interact with specific anti Legionella antibodies. J Bacteriol 160:199–203

    Google Scholar 

  • Horwitz MA (1983a) Formation of a novel phagosome by the legionnaires’ disease bacterium Legionella pneumophila) in human monocytes. J Exp Med 158:1319–1331

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA (1983b) The legionnaires’ disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J Exp Med 158:2108–2126

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA (1983c) Cell-mediated immunity in legionnaires’ disease. J Clin Invest 71:1686–1697

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA (1984) Phagocytosis of the legionnaires’ disease bacterium (Legionella pneumophila) occurs by a novel mechanism:engulfment within a pseudopod coil. Cell 36:27–33

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA (1987) Characterization of avirulent mutant Legionella pneumophila that survive but do not multiply within human monocytes. J Exp Med 166:1310–1328

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA (1989) The immunobiology of Legionella pneumophila. In: Mounder JW (ed) Intracellular parasitism. CRC Press, Boca Raton, pp 141–156

    Google Scholar 

  • Horwitz MA (1993) State-of-the-art address. Toward an understanding of host and bacterial molecules mediating Legionella pneumophila pathogenesis. Legionella, current status and emerging perspectives. Barbaree J, Breiman R, Dufour AP (eds) In: American Society of Microbiology, Washington DC, pp 55–62

    Google Scholar 

  • Horwitz MA, Silverstein SC (1981c) Activated human monocytes inhibit the intracellular multiplication of legionnaires’ disease bacteria. J Exp Med 154:1618–1635

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA, Maxfield FR (1984) Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J Cell Biol 99:1936–1943

    Article  PubMed  CAS  Google Scholar 

  • Jones TC, Hirsch JG (1972) The interaction between Toxoplasma gondii and mammalian cells. II. The absence of lysosomal fusion with phagocytic vacuoles containing living parasites. J Exp Med 136:1173–1194

    CAS  Google Scholar 

  • Horwitz MA, Silverstein SC (1980) The legionnaires’ disease bacterium (Legionella pneumophila) multiplies intracellularly in human monocytes. J Clin Invest 66:441–450

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA, Silverstein SC (1981a) Interaction of the legionnaires’ disease bacterium (Legionella pneumophila) with human phagocytes. I. L pneumophila resists killing by polymorphonuclear leukocytes, antibody, and complement. J Exp Med 153:386–397

    Article  PubMed  CAS  Google Scholar 

  • Horwitz MA, Silverstein SC (1981b) Interaction of the legionnaires’ disease bacterium (Legionella pneumophila) with human phagocytes. II. Antibody promotes binding of L. pneumophila to monocytes but does not inhibit intracellular multiplication. J Exp Med 153:398–406

    Article  PubMed  CAS  Google Scholar 

  • Jones TC, Yeh S, Hirsch JG (1972) The interaction between Toxoplasma gondii and mammalian cells. I. Mechanism of entry and intracellular fate of the parasite. J Exp Med 136:1157–1172

    Article  PubMed  CAS  Google Scholar 

  • Marra A, Horwitz MA, Shuman HA (1990) The HL-60 model for the interaction of human macrophages with the legionnaires’ disease bacterium. J Immunol 144:2738–2744

    PubMed  CAS  Google Scholar 

  • Marra A, Blander SJ, Horwitz MA, Shuman HA (1992) Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc Natl Acad Sci USA 89:9607–9611

    Article  PubMed  CAS  Google Scholar 

  • Mengaud, J, MA Horwitz (1993) The major iron-containing protein of Legionella pneumophila is an aconitase homologous with the human iron-responsive element-binding protein. J Bacteriol 175:5666–5676

    PubMed  CAS  Google Scholar 

  • Moffat JF, Edelstein PH, Regula DP Jr, Cirillo JD, Tompkins LS (1994) Effects of an isogenic Znmetalloprotease-deficient mutant of Legionella pneumophila in a guinea-pig pneumonia model. Mol Microbiol 12:693–705

    Article  PubMed  CAS  Google Scholar 

  • Mosser DM, Edelson PG (1985) The mouse macrophage receptor for C3bi (CR3) is a major mechanism in the phagocytosis of Leishmania promastigotes. J Immunol 135:2785–2789

    PubMed  CAS  Google Scholar 

  • Nogueira N, Cohn ZA (1976) Trypanosoma cruzi mechanism of entry and intracellular fate in mammalian cells. J Exp Med 143:1402–1420

    Article  PubMed  CAS  Google Scholar 

  • Payne NR, Horwitz MA (1987) Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors. J Exp Med 166:1377–1389

    Article  PubMed  CAS  Google Scholar 

  • Quinn FD, Tompkins LS (1989) Analysis of a cloned sequence of Legionella pneumophila encoding a 38-kDa metalloprotease possessing haemolytic and cytotoxic activities. Mol Microbiol 3:797–805

    Article  PubMed  CAS  Google Scholar 

  • Sadosky AB, Wiater LA, Shuman HA (1993) Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Intact Immun 61:5361–5373

    CAS  Google Scholar 

  • Sadosky AB, Wilson JW, Steinman HM, Shuman HA (1994) The iron Superoxide dismutase of Legionella pneumophila is essential for viability. J Bacteriol 176:3790–3799

    PubMed  CAS  Google Scholar 

  • Saukkonen K, Cabellos C, Burroughs M, Prasad S, Tuomanen E (1991) Integrin-mediated localization of Bordetella pertussis within macrophages:role in pulmonary colonization. J Exp Med 173:1143–1149

    Article  PubMed  CAS  Google Scholar 

  • Schlesinger LS, Horwitz MA (1990a) Phagocytosis of leprosy bacilli is mediated by complement receptors CR1 and CR3 on human monocytes and complement component C3 in serum. J Clin Invest 85:1304–1314

    Article  PubMed  CAS  Google Scholar 

  • Schlesinger LS, Horwitz MA (1990b) Complement receptors and complement component C3 mediate phagocytosis of Mycobactehum tuberculosis and Mycobacterium leprae. Int J Lepr 58:200–201

    Google Scholar 

  • Schlesinger LS, Bellinger-Kawahara CG, Payne NR, Horwitz MA (1990) Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. J Immunol 144:2771–2780

    PubMed  CAS  Google Scholar 

  • Sibley LD, Weidner E, Krahenbuhl JL (1985) Phagosome acidification blocked by intracellular Toxoplasma gondli. Nature 315:416–419

    Article  PubMed  CAS  Google Scholar 

  • Steinman, HM (1992) Construction of an Escherichia coli K-12 strain deleted for manganese and iron Superoxide dismutase genes and its use in cloning the iron Superoxide dismutase gene of Legionella pneumophila. Mol Gen Genet 232:427–430

    Article  PubMed  CAS  Google Scholar 

  • Stevens DR, Moulton JE (1978) Ultrastructural and immunological aspects of the phagocytosis of Trypanosoma brucei by mouse peritoneal macrophages. Infect Immun 19:972–982

    PubMed  CAS  Google Scholar 

  • Szczepanski A, Fleit HB (1988) Interaction between Borrelia burgdorferi and polymorphonuclear leukocytes. Phagocytosis and the induction of the respiratory burst. Ann NY Acad Sci 539:425–428

    Article  Google Scholar 

  • Szeto L, Shuman HA (1990) The major secreted protein (MSP) of Legionella pneumophila, a protease, is not required for intracellular growth or host cell killng. Infect Immun 58:2585–2592

    PubMed  CAS  Google Scholar 

  • Tanowitz H, Wittner M, Kress Y, Bloom B (1975) Studies of in vitro infection by Trypanosoma cruzi. I. Ultrastructural studies on the invasion of macrophages and L-cells. Am J Trop Med Hyg 25:25–33

    Google Scholar 

  • Wiater LA, Sadosky AB, Shuman HA (1994) Transposon mutagenesis of Legionella pneumophila with Tn903dll lacZ identification of a growth phase-regulated pigmentation gene. Mol Microbiol 11:641–653

    Article  PubMed  CAS  Google Scholar 

  • Wilson ME, Pearson RD (1987) Roles of CR3 and mannose receptors in the attachment and ingestion of Leishmania donovani by human mononuclear phagocytes. Infect Immun 56:363–369

    Google Scholar 

  • Wright SD, Silverstein SC (1983) Receptors for C3b and C3bi promote phagocytosis but not release of toxic oxygen from human phagocytes. J Exp Med 158:2016–2023

    Article  PubMed  CAS  Google Scholar 

  • Wyrick PB, Brownridge EA (1978) Growth of Chlamydia psittaci in macrophages. Infect Immun 19:1054–1060

    PubMed  CAS  Google Scholar 

  • Yamamoto K, Johnston RB jr (1984) Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages. J Exp Med 159:405–416

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Microbiology, College of Physicians and Surgeons, Columbia University, 701 West 168th Street, New York, NY, 10032, USA

    H. A. Shuman

  2. Division of Infectious Diseases, Department of Medicine, School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA, 90024, USA

    M. A. Horwitz

Authors
  1. H. A. Shuman
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  2. M. A. Horwitz
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Editor information

Editors and Affiliations

  1. Department of Microbiology and Molecular Genetics, University of California, Los Angeles, 405 Hilgard Avenue, Los Angeles, CA, 90095, USA

    Virginia L. Miller Ph.D.

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© 1996 Springer-Verlag Berlin Heidelberg

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Shuman, H.A., Horwitz, M.A. (1996). Legionella pneumophila Invasion of Mononuclear Phagocytes. In: Miller, V.L. (eds) Bacterial Invasiveness. Current Topics in Microbiology and Immunology, vol 209. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85216-9_6

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  • DOI: https://doi.org/10.1007/978-3-642-85216-9_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-85218-3

  • Online ISBN: 978-3-642-85216-9

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