Replication of Legionella pneumophila in human cells: Why are we susceptible?

Frontiers in Microbiology

Volumn 1, Issue DEC, 2010, Pages

  Khweek, Arwa Abu ^a   Amer, Amal ^a  

^a OHIO STATE UNIVERSITY   (United States)

Author keywords

Neuronal apoptosis inhibitory proteins; NOD like receptors; Pathogen associated molecular patterns; Toll like receptors

Indexed keywords

EID: 84855176661     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2010.00133     Document Type: Article

References (103)

1. Abdelaziz, D. H., Amr, K., and Amer, A. O. (2010). Nlrc4/Ipaf/CLAN/CARD12: more than a flagellin sensor. Int. J. Biochem. Cell Biol. 42, 789-791.
2. Abu Kwaik, Y., Eisenstein, B. I., and Engleberg, N. C. (1993). Phenotypic modulation by Legionella pneumophila upon infection of macrophages. Infect. Immun. 61, 1320-1329.
3. Abu-Zant, A., Jones, S., Asare, R., Suttles, J., Price, C., Graham, J., and Kwaik, Y. A. (2007). Anti-apoptotic signalling by the Dot/Icm secretion system of L. pneumophila. Cell. Microbiol. 9, 246-264.
4. Akhter, A., Gavrilin, M. A., Frantz, L., Washington, S., Ditty, C., Limoli, D., Day, C., Sarkar, A., Newland, C., Butchar, J., Marsh, C. B., Wewers, M. D., Tridandapani, S., Kanneganti, T.-D., and Amer, A. O. (2009). Caspase-7 activation by the Nlrc4/Ipaf inflammasome restricts Legionella pneumophila infection. PLoS Pathog. 5, e1000361. doi: 10.1371/journal.ppat.1000361.
5. Akira, S., Uematsu, S., and Takeuchi, O. (2006). Pathogen recognition and innate immunity. Cell 124, 783-801.
6. Al-Khodor, S., Price, C. T., Habyarimana, F., Kalia, A., and Abu Kwaik, Y. (2008). A Dot/Icm-translocated ankyrin protein of Legionella pneumophila is required for intracellular proliferation within human macrophages and protozoa. Mol. Microbiol. 70, 908-923.
7. Amer, A., Franchi, L., Kanneganti, T. D., Body-Malapel, M., Ozören, N., Brady, G., Meshinchi, S., Jagirdar, R., Gewirtz, A., Akira, S., and Núñez, G. (2006). Regulation of Legionella phagosome maturation and infection through flagellin and host Ipaf. J. Biol. Chem. 281, 35217-35223.
8. Amer, A. O. (2010). Modulation of caspases and their non-apoptotic functions by Legionella pneumophila. Cell. Microbiol. 12, 140-147.
9. Archer, K. A., Alexopoulou, L., Flavell, R. A., and Roy, C. R. (2009). Multiple MyD88-dependent responses contribute to pulmonary clearance of Legionella pneumophila. Cell. Microbiol. 11, 21-36.
10. Barker, J., Brown, M. R., Collier, P. J., Farrell, I., and Gilbert, P. (1992). Relationship between Legionella pneumophila and Acanthamoeba polyphaga: physiological status and susceptibility to chemical inactivation. Appl. Environ. Microbiol. 58, 2420-2425.
11. Barker, J., Scaife, H., and Brown, M. R. (1995). Intraphagocytic growth induces an antibiotic-resistant phenotype of Legionella pneumophila. Antimicrob. Agents Chemother. 39, 2684-2688.
12. Bartfeld, S., Engels, C., Bauer, B., Aurass, P., Flieger, A., Bruggemann, H., and Meyer, T. F. (2009). Temporal resolution of two-tracked NF-kappaB activation by Legionella pneumophila. Cell. Microbiol. 11, 1638-1651.
13. Beckers, M. C., Yoshida, S., Morgan, K., Skamene, E., and Gros, P. (1995). Natural resistance to infection with Legionella pneumophila: chromosomal localization of the Lgn1 susceptibility gene. Mamm. Genome 6, 540-545.
14. Bhardwaj, N., Nash, T. W., and Horwitz, M. A. (1986). Interferon-gamma-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila. J. Immunol. 137, 2662-2669.
15. Blanchard, D. K., Djeu, J. Y., Klein, T. W., Friedman, H., and Stewart, W. E. (1987). Induction of tumor necrosis factor by Legionella pneumophila. Infect. Immun. 55, 433-437.
16. Bozue, J. A., and Johnson, W. (1996). Interaction of Legionella pneumophila with Acanthamoeba castellanii: uptake by coiling phagocytosis and inhibition of phagosome-lysosome fusion. Infect. Immun. 64, 668-673.
17. Byrd, T. F., and Horwitz, M. A. (2000). Aberrantly low transferrin receptor expression on human monocytes is associated with nonpermissiveness for Legionella pneumophila growth. J. Infect. Dis. 181, 1394-1400.
18. Carratala, J., Gudiol, F., Pallares, R., Dorca, J., Verdaguer, R., Ariza, J., and Manresa, F. (1994). Risk factors for nosocomial Legionella pneumophila pneumonia. Am. J. Respir. Crit. Care Med. 149(Pt 1), 625-629.
19. Cazalet, C., Rusniok, C., Brüggemann, H., Zidane, N., Magnier, A., Ma, L., Tichit, M., Jarraud, S., Bouchier, C., Vandenesch, F., Kunst, F., Etienne, J., Glaser, P., and Buchrieser, C. (2004). Evidence in the Legionella pneumophila genome for exploitation of host cell functions and high genome plasticity. Nat. Genet. 36, 1165-1173.
20. Cianciotto, N. P. (2007). Iron acquisition by Legionella pneumophila. Biometals 20, 323-331
21. Cirillo, J. D., Falkow, S., and Tompkins, L. S. (1994). Growth of Legionella pneumophila in Acanthamoeba castellanii enhances invasion. Infect. Immun. 62, 3254-3261.
22. Coers, J., Vance, R. E., Fontana, M. F., and Dietrich, W. F. (2007). Restriction of Legionella pneumophila growth in macrophages requires the concerted action of cytokine and Naip5/Ipaf signalling pathways. Cell. Microbiol. 9, 2344-2357.
23. Craig, K. L., and Tyers, M. (1999). The F-box: a new motif for ubiquitin dependent proteolysis in cell cycle regulation and signal transduction. Prog. Biophys. Mol. Biol. 72, 299-328.
24. Creagh, E. M., Conroy, H., and Martin, S. J. (2003). Caspase-activation pathways in apoptosis and immunity. Immunol. Rev. 193, 10-21.
25. Damiano, J. S., Stehlik, C., Pio, F., Godzik, A., and Reed, J. C. (2001). CLAN, a novel human CED-4-like gene. Genomics 75, 77-83.
26. Den Boer, J. W., Yzerman, E. P., Schellekens, J., Lettinga, K. D., Boshuizen, H. C., Van Steenbergen, J. E., Bosman, A., Van den Hof, S., Van Vliet, H. A., Peeters, M. F., Van Ketel, R. J., Speelman, P., Kool, J. L., and Conyn-Van Spaendonck, M. A. (2002). A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999. Emerging Infect. Dis. 8, 37-43.
27. Diez, E., Lee, S. H., Gauthier, S., Yaraghi, Z., Tremblay, M., Vidal, S., and Gros, P. (2003). Birc1e is the gene within the Lgn1 locus associated with resistance to Legionella pneumophila. Nat. Genet. 33, 55-60.
28. Fink, S. L., and Cookson, B. T. (2005). Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells. Infect. Immun. 73, 1907-1916.
29. Fliermans, C. B., Cherry, W. B., Orrison, L. H., Smith, S. J., Tison, D. L., and Pope, D. H. (1981). Ecological distribution of Legionella pneumophila. Appl. Environ. Microbiol. 41, 9-16.
30. Fraser, D. W., Deubner, D. C., Hill, D. L., and Gilliam, D. K. (1979). Nonpneumonic, short-incubation-period Legionellosis (Pontiac fever) in men who cleaned a steam turbine condenser. Science 205, 690-691.
31. Friedman, H., Yamamoto, Y., and Klein, T. W. (2002). Legionella pneumophila pathogenesis and immunity. Semin. Pediatr. Infect. Dis. 13, 273-279.
32. Gao, L. Y., and Abu Kwaik, Y. (1999a). Activation of caspase 3 during Legionella pneumophila-induced apoptosis. Infect. Immun. 67, 4886-4894.
33. Gao, L. Y., and Abu Kwaik, Y. (1999b). Apoptosis in macrophages and alveolar epithelial cells during early stages of infection by Legionella pneumophila and its role in cytopathogenicity. Infect. Immun. 67, 862-870.
34. Gebran, S. J., Newton, C., Yamamoto, Y., Widen, R., Klein, T. W., and Friedman, H. (1994). Macrophage permissiveness for Legionella pneumophila growth modulated by iron. Infect. Immun. 62, 564-568.
35. Goldstein, E., Lippert, W., and Warshauer, D. (1974). Pulmonary alveolar macrophage. Defender against bacterial infection of the lung. J. Clin. Invest. 54, 519-528.
36. Green, G. M. (1970). The J. Burns Amberson Lecture - in defense of the lung. Am. Rev. Respir. Dis. 102, 691-703.
37. Hatakeyama, S., Yada, M., Matsumoto, M., Ishida, N., and Nakayama, K. I. (2001). U box proteins as a new family of ubiquitin-protein ligases. J. Biol. Chem. 276, 33111-33120.
38. Hawn, T. R., Berrington, W. R., Smith, I. A., Uematsu, S., Akira, S., Aderem, A., Smith, K. D., and Skerrett, S. J. (2007). Altered inflammatory responses in TLR5-deficient mice infected with Legionella pneumophila. J. Immunol. 179, 6981-6987.
39. Hawn, T. R., Verbon, A., Lettinga, K. D., Zhao, L. P., Li, S. S., Laws, R. J. Skerrett, S. J., Beutler, B., Schroeder, L., Nachman, A., Ozinsky, A., Smith, K. D., and Aderem, A. (2003). A common dominant TLR5 stop codon polymorphism abolishes flagellin signaling and is associated with susceptibility to legionnaires' disease. J. Exp. Med. 198, 1563-1572.
40. Hawn, T. R., Verbon, A., Janer, M., Zhao, L. P., Beutler, B., and Aderem, A. (2005). Toll-like receptor 4 polymorphisms are associated with resistance to Legionnaires' disease. Proc. Natl. Acad. Sci. U.S.A. 102, 2487-2489.
41. Hayashi, F., Smith, K. D., Ozinsky, A., Hawn, T. R., Yi, E. C., Goodlett, D. R., Eng, J. K., Akira, S., Underhill, D. M., and Aderem, A. (2001). The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5. Nature 410, 1099-1103.
42. Herpers, B. L., Yzerman, E. P., de Jong, B. A., Bruin, J. P., Lettinga, K. D., Kuipers, S., Den Boer, J. W., van Hannen, E. J., Rijkers, G. T., van Velzen-Blad, H., and de Jongh, B. M. (2009). Deficient mannose-binding lectin-mediated complement activation despite mannose-binding lectin-sufficient genotypes in an outbreak of Legionella pneumophila pneumonia. Hum. Immunol. 70, 125-129.
43. Horwitz, M. A. (1983a). Formation of a novel phagosome by the Legionnaires' disease bacterium (Legionella pneumophila) in human monocytes. J. Exp. Med. 158, 1319-1331.
44. Horwitz, M. A. (1983b). The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J. Exp. Med. 158, 2108-2126.
45. Horwitz, M. A. (1984). Phagocytosis of the Legionnaires' disease bacterium (Legionella pneumophila) occurs by a novel mechanism: engulfment within a pseudopod coil. Cell 36, 27-33.
46. Horwitz, M. A., and Maxfield, F. R. (1984). Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J. Cell Biol. 99, 1936-1943.
47. Horwitz, M. A., and Silverstein, S. C. (1980). Legionnaires' disease bacterium (Legionella pneumophila) multiples intracellularly in human monocytes. J. Clin. Invest. 66, 441-450.
48. Horwitz, M. A., and Silverstein, S. C. (1981a). Activated human monocytes inhibit the intracellular multiplication of Legionnaires' disease bacteria. J. Exp. Med. 154, 1618-1635.
49. Horwitz, M. A., and Silverstein, S. C. (1981b). 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.
50. Isberg, R. R., O'Connor, T. J., and Heidtman, M. (2009). The Legionella pneumophila replication vacuole: making a cosy niche inside host cells. Nat. Rev. Microbiol. 7, 13-24.
51. Ivanov, S. S., and Roy, C. R. (2009). Modulation of ubiquitin dynamics and suppression of DALIS formation by the Legionella pneumophila Dot/Icm system. Cell. Microbiol. 11, 261-278.
52. Janeway, C. A. Jr., and Medzhitov, R. (2002). Innate immune recognition. Annu. Rev. Immunol. 20, 197-216.
53. Kagan, J. C., and Roy, C. R. (2002). Legionella phagosomes intercept vesicular traffic from endoplasmic reticulum exit sites. Nat. Cell Biol. 4, 945-954.
54. Kuiper, M. W., Wullings, B. A., Akkermans, A. D., Beumer, R. R., and van der Kooij, D. (2004). Intracellular proliferation of Legionella pneumophila in Hartmannella vermiformis in aquatic biofilms grown on plasticized polyvinyl chloride. Appl. Environ. Microbiol. 70, 6826-6833.
55. Lettinga, K. D., Verbon, A., Weverling, G. J., Schellekens, J. F., Den Boer, J. W., Yzerman, E. P., Prins, J., Boersma, W. G., van Ketel, R. J., Prins, J. M., and Speelman, P. (2002). Legionnaires' disease at a Dutch flower show: prognostic factors and impact of therapy. Emerging Infect. Dis. 8, 1448-1454.
56. Lettinga, K. D., Weijer, S., Speelman, P., Prins, J. M., Van Der Poll, T., and Verbon, A. (2003). Reduced interferon-gamma release in patients recovered from Legionnaires' disease. Thorax 58, 63-67.
57. Li, J., and Yuan, J. (2008). Caspases in apoptosis and beyond. Oncogene 27, 6194-6206.
58. Liang, J. L., Dziuban, E. J., Craun, G. F., Hill, V., Moore, M. R., Gelting, R. J., Calderon, R. L., Beach, M. J., Roy, S. L. and Centers for Disease Control and Prevention (CDC). (2006). Surveillance for waterborne disease and outbreaks associated with drinking water and water not intended for drinking - United States, 2003-2004. MMWR Surveill. Summ. 55, 31-65.
59. Liles, M.R., Scheel, T. A., and Cianciotto, N. P. (2000). Discovery of a nonclassical siderophore, legiobactin, produced by strains of Legionella pneumophila. J. Bacteriol. 182, 749-757.
60. Liston, P., Roy, N., Tamai, K., Lefebvre, C., Baird, S., Cherton-Horvat, G., Farahani, R., McLean, M., Ikeda, J. E., MacKenzie, A., and Korneluk, R. G. (1996). Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 379, 349-353.
61. Lomma, M., Dervins-Ravault, D., Rolando, M., Nora, T., Newton, H. J., Samson, F. M., Sahr, T., Gomez-Valero, L., Jules, M., Hartland, E. L., and Buchrieser, C. (2010). The Legionella pneumophila F-box protein Lpp2082 (AnkB) modulates ubiquitination of the host protein parvin B and promotes intracellular replication. Cell. Microbiol. 12, 1272-1291.
62. Losick, V. P., and Isberg, R. R. (2006). NF-kappaB translocation prevents host cell death after low-dose challenge by Legionella pneumophila. J. Exp. Med. 203, 2177-2189.
63. Marra, A., Horwitz, M. A., and Shuman, H. A. (1990). The HL-60 model for the interaction of human macrophages with the Legionnaires' disease bacterium. J. Immunol. 144, 2738-2744.
64. Marston, B. J., Lipman, H. B., and Breiman, R. F. (1994). Surveillance for Legionnaires' disease. Risk factors for morbidity and mortality. Arch. Intern. Med. 154, 2417-2422.
65. Marston, B. J., Plouffe, J. F., File, T. M., Jr., Hackman, B. A., Salstrom, S. J., Lipman, H. B., Kolczak, M. S., and Breiman, R. F. (1997). Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group. Arch. Intern. Med. 157, 1709-1718.
66. Martinon, F., and Tschopp, J. (2004). Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell 117, 561-574.
67. Maruta, K., Miyamoto, H., Hamada, T., Ogawa, M., Taniguchi, H., and Yoshida, S. (1998). Entry and intracellular growth of Legionella dumoffii in alveolar epithelial cells. Am. J. Respir. Crit. Care Med. 157(Pt 1), 1967-1974.
68. Matsiota-Bernard, P., Lefebre, C., Sedqui, M., Cornillet, P., and Guenounou, M. (1993). Involvement of tumor necrosis factor alpha in intracellular multiplication of Legionella pneumophila in human monocytes. Infect. Immun. 61, 4980-4983.
69. Molmeret, M., Zink, S. D., Han, L., Abu-Zant, A., Asari, R., Bitar, D. M., and Abu Kwaik, Y. (2004). Activation of caspase-3 by the Dot/Icm virulence system is essential for arrested biogenesis of the Legionella-containing phagosome. Cell. Microbiol. 6, 33-48.
70. Nash, T. W., Libby, D. M., and Horwitz, M. A. (1984). Interaction between the legionnaires' disease bacterium (Legionella pneumophila) and human alveolar macrophages. Influence of antibody, lymphokines, and hydrocortisone. J. Clin. Invest. 74, 771-782.
71. Nash, T. W., Libby, D. M., and Horwitz, M. A. (1988). IFN-gamma-activated human alveolar macrophages inhibit the intracellular multiplication of Legionella pneumophila. J. Immunol. 140, 3978-3981.
72. Neumeister, B. (2004). Intracellular multiplication of Legionella species and the influence of amoebae on their intracellular growth in human monocytes: mono mac 6 cells and Acanthamoeba castellanii as suitable in vitro models. Methods Mol. Biol. 268, 141-151.
73. Neumeister, B., Bach, V., Faigle, M., and Northoff, H. (2001). Induction of iNOS in human monocytes infected with different Legionella species. FEMS Microbiol. Lett. 202, 31-38.
74. Neumeister, B., Schoniger, S., Faigle, M., Eichner, M., and Dietz, K. (1997). Multiplication of different Legionella species in Mono Mac 6 cells and in Acanthamoeba castellanii. Appl. Environ. Microbiol. 63, 1219-1224.
75. Park, D. R., and Skerrett, S. J. (1996). IL-10 enhances the growth of Legionella pneumophila in human mononuclear phagocytes and reverses the protective effect of IFN-gamma: differential responses of blood monocytes and alveolar macrophages. J. Immunol. 157, 2528-2538.
76. Payne, N. R., and Horwitz, M. A. (1987). Phagocytosis of Legionella pneumophila is mediated by human monocyte complement receptors. J. Exp. Med. 166, 1377-1389.
77. Pearlman, E., Jiwa, A. H., Engleberg, N. C., and Eisenstein, B. I. (1988). Growth of Legionella pneumophila in a human macrophage-like (U937) cell line. Microb. Pathog. 5, 87-95.
78. Poyet, J.L., Srinivasula, S. M., Tnani, M., Razmara, M., Fernandes-Alnemri, T., and Alnemri, E. S. (2001). Identification of Ipaf, a human caspase-1-activating protein related to Apaf-1. J. Biol. Chem. 276, 28309-28313.
79. Price, C. T., Al-Khodor, S., Al-Quadan, T., Santic, M., Habyarimana, F., Kalia, A., and Kwaik, Y. A. (2009). Molecular mimicry by an F-box effector of Legionella pneumophila hijacks a conserved polyubiquitination machinery within macrophages and protozoa. PLoS Pathog. 5, e1000704. doi: 10.1371/journal.ppat.1000704.
80. Radtke, A. L., and O'Riordan, M. X. (2006). Intracellular innate resistance to bacterial pathogens. Cell. Microbiol. 8, 1720-1729.
81. Rogers, J., Dowsett, A. B., Dennis, P. J., Lee, J. V., and Keevil, C. W. (1994). Influence of plumbing materials on biofilm formation and growth of Legionella pneumophila in potable water systems. Appl. Environ. Microbiol. 60, 1842-1851.
82. Rovera, G., Santoli, D., and Damsky, C. (1979). Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc. Natl. Acad. Sci. U.S.A. 76, 2779-2783.
83. Rowbotham, T. J. (1980). Preliminary report on the pathogenicity of Legionella pneumophila for freshwater and soil amoebae. J. Clin. Pathol. 33, 1179-1183.
84. Rowbotham, T. J. (1986). Current views on the relationships between amoebae, legionellae and man. Isr. J. Med. Sci. 22, 678-689.
85. Santic, M., Asare, R., Doric, M., and Abu Kwaik, Y. (2007). Host-dependent trigger of caspases and apoptosis by Legionella pneumophila. Infect. Immun. 75, 2903-2913.
86. Santic, M., Molmeret, M., and Abu Kwaik, Y. (2005). Maturation of the Legionella pneumophila-containing phagosome into a phagolysosome within gamma interferon-activated macrophages. Infect. Immun. 73, 3166-3171.
87. Schmeck, B., N'Guessan, P. D., Ollomang, M., Lorenz, J., Zahlten, J., Opitz, B., Flieger, A., Suttorp, N., and Hippenstiel, S. (2007). Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells. Eur. Respir. J. 29, 25-33.
88. Sethi, K. K., and Brandis, H. (1983). Direct demonstration and isolation of Legionella pneumophila (serogroup 1) from bathroom water specimens in a hotel. Zentralbl. Bakteriol. Mikrobiol. Hyg. B 177, 402-405.
89. Spitalny, K. C., Vogt, R. L., Orciari, L. A., Witherell, L. E., Etkind, P., and Novick, L. F. (1984). Pontiac fever associated with a whirlpool spa. Am. J. Epidemiol. 120, 809-817.
90. Swanson, M. S., and Isberg, R. R. (1995). Association of Legionella pneumophila with the macrophage endoplasmic reticulum. Infect. Immun. 63, 3609-3620.
91. Takahashi, R., Deveraux, Q., Tamm, I., Welsh, K., Assa-Munt, N., Salvesen, G. S., and Reed, J. C. (1998). A single BIR domain of XIAP sufficient for inhibiting caspases. J. Biol. Chem. 273, 7787-7790.
92. Takeda, K., Kaisho, T., and Akira, S. (2003). Toll-like receptors. Annu. Rev. Immunol. 21, 335-376.
93. Turner, M. W. (1996). Mannose-binding lectin: the pluripotent molecule of the innate immune system. Immunol. Today 17, 532-540.
94. Underhill, D. M., Ozinsky, A., Smith, K. D. and Aderem, A. (1999). Toll-like receptor-2 mediates mycobacteria-induced proinflammatory signaling in macrophages. Proc. Natl. Acad. Sci. U.S.A. 96, 14459-14463.
95. Vinzing, M., Eitel, J., Lippmann, J., Hocke, A. C., Zahlten, J., Slevogt, H., N'guessan, P. D., Günther, S., Schmeck, B., Hippenstiel, S., Flieger, A., Suttorp, N., and Opitz, B. (2008). NAIP and Ipaf control Legionella pneumophila replication in human cells. J. Immunol. 180, 6808-6815.
96. Viswanathan, V. K., Edelstein, P. H., Pope, C. D., and Cianciotto, N. P. (2000). The Legionella pneumophila iraAB locus is required for iron assimilation, intracellular infection, and virulence. Infect. Immun. 68, 1069-1079.
97. Walsh, J. G., Cullen, S. P., Sheridan, C., Luthi, A. U., Gerner, C., and Martin, S. J. (2008). Executioner caspase-3 and caspase-7 are functionally distinct proteases. Proc. Natl. Acad. Sci. U.S.A. 105, 12815-12819.
98. Watnick, P., and Kolter, R. (2000). Biofilm, city of microbes. J. Bacteriol. 182, 2675-2679.
99. Winn, W. C. Jr., and Myerowitz, R. L. (1981). The pathology of the Legionella pneumonias. A review of 74 cases and the literature. Hum. Pathol. 12, 401-422.
100. Wright, E. K., Goodart, S. A., Growney, J. D., Hadinoto, V., Endrizzi, M. G., Long, E. M., Sadigh, K., Abney, A. L., Bernstein-Hanley, I., and Dietrich, W. F. (2003). Naip5 affects host susceptibility to the intracellular pathogen Legionella pneumophila. Curr. Biol. 13, 27-36.
101. Yu, V. L., Plouffe, J. F., Pastoris, M. C., Stout, J. E., Schousboe, M., Widmer, A., Summersgill, J., File, T., Heath, C. M., Paterson, D. L., and Chereshsky, A. (2002). Distribution of Legionella species and serogroups isolated by culture in patients with sporadic community-acquired legionellosis: an international collaborative survey. J. Infect. Dis. 186, 127-128.
102. Ziegler-Heitbrock, H. W., Thiel, E., Futterer, A., Herzog, V., Wirtz, A., and Riethmuller, G. (1988). Establishment of a human cell line (Mono Mac 6) with characteristics of mature monocytes. Int. J. Cancer 41, 456-461.
103. Zink, S. D., Pedersen, L., Cianciotto, N. P., and Abu-Kwaik, Y. (2002). The Dot/Icm type IV secretion system of Legionella pneumophila is essential for the induction of apoptosis in human macrophages. Infect. Immun. 70, 1657-1663.