Control of host cell phosphorylation by Legionella pneumophila

Frontiers in Microbiology

Volumn 2, Issue APR, 2011, Pages

  Haenssler, Eva ^a   Isberg, Ralph R ^a  

^a TUFTS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Legionella; Mitogen activated protein kinase; NF B; Phosphatidylinositol 3 kinase

Indexed keywords

EID: 83655174194     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2011.00064     Document Type: Article

References (101)

1. 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.
2. Adkins, I., Koberle, M., Grobner, S., Bohn, E., Autenrieth, I. B., and Borgmann, S. (2007). Yersinia outer proteins E, H, P, and T differentially target the cytoskeleton and inhibit phagocytic capacity of dendritic cells. Int. J. Med. Microbiol. 297, 235-244.
3. Ahn, K. S., and Aggarwal, B. B. (2005). Transcription factor NF-κB: a sensor for smoke and stress signals. Ann. N. Y. Acad. Sci. 1056, 218-233.
4. Back, S. H., Scheuner, D., Han, J., Song, B., Ribick, M., Wang, J., Gildersleeve, R. D., Pennathur, S., and Kaufman, R. J. (2009). Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells. Cell Metab. 10, 13-26.
5. Backert, S., Ziska, E., Brinkmann, V., Zimny-Arndt, U., Fauconnier, A., Jungblut, P. R., Naumann, M., and Meyer, T. F. (2000). Translocation of the Helicobacter pylori CagA protein in gastric epithelial cells by a type IV secretion apparatus. Cell. Microbiol. 2, 155-164.
6. Banga, S., Gao, P., Shen, X., Fiscus, V., Zong, W. X., Chen, L., and Luo, Z. Q. (2007). Legionella pneumophila inhibits macrophage apoptosis by targeting pro-death members of the Bcl2 protein family. Proc. Natl. Acad. Sci. U.S.A. 104, 5121-5126.
7. Bartfeld, S., Engels, C., Bauer, B., Aurass, P., Flieger, A., Bruggemann, H., and Meyer, T. F. (2009). Temporal resolution of two-tracked NF-κB activation by Legionella pneumophila. Cell. Microbiol. 11, 1638-1651.
8. Belyi, Y., Niggeweg, R., Opitz, B., Vogelsgesang, M., Hippenstiel, S., Wilm, M., and Aktories, K. (2006). Legionella pneumophila glucosyltransferase inhibits host elongation factor 1A. Proc. Natl. Acad. Sci. U.S.A. 103, 16953-16958.
9. Belyi, Y., Tabakova, I., Stahl, M., and Aktories, K. (2008). Lgt: a family of cytotoxic glucosyltransferases produced by Legionella pneumophila. J. Bacteriol. 190, 3026-3035.
10. Beresford, N., Patel, S., Armstrong, J., Szoor, B., Fordham-Skelton, A. P., and Tabernero, L. (2007). MptpB, a virulence factor from Mycobacterium tuberculosis, exhibits triple-specificity phosphatase activity. Biochem. J. 406, 13-18.
11. Berger, K. H., Merriam, J. J., and Isberg, R. R. (1994). Altered intracellular targeting properties associated with mutations in the Legionella pneumophila dotA gene. Mol. Microbiol. 14, 809-822.
12. Brandt, S., Kwok, T., Hartig, R., Konig, W., and Backert, S. (2005). NF-κB activation and potentiation of proinflammatory responses by the Helicobacter pylori CagA protein. Proc. Natl. Acad. Sci. U.S.A. 102, 9300-9305.
13. Brombacher, E., Urwyler, S., Ragaz, C., Weber, S. S., Kami, K., Overduin, M., and Hilbi, H. (2009). Rab1 guanine nucleotide exchange factor SidM is a major phosphatidylinositol 4-phosphate-binding effector protein of Legionella pneumophila. J. Biol. Chem. 284, 4846-4856.
14. Bruggemann, H., Cazalet, C., and Buchrieser, C. (2006a). Adaptation of Legionella pneumophila to the host environment: role of protein secretion, effectors and eukaryotic-like proteins. Curr. Opin. Microbiol. 9, 86-94.
15. Bruggemann, H., Hagman, A., Jules, M., Sismeiro, O., Dillies, M. A., Gouyette, C., Kunst, F., Steinert, M., Heuner, K., Coppee, J. Y., and Buchrieser, C. (2006b). Virulence strategies for infecting phagocytes deduced from the in vivo transcriptional program of Legionella pneumophila. Cell. Microbiol. 8, 1228-1240.
16. Burstein, D., Zusman, T., Degtyar, E., Viner, R., Segal, G., and Pupko, T. (2009). Genome-scale identification of Legionella pneumophila effectors using a machine learning approach. PLoS Pathog. 5, e1000508. doi: 10.1371/journal.ppat.1000508
17. Charpentier, X., Gabay, J. E., Reyes, M., Zhu, J. W., Weiss, A., and Shuman, H. A. (2009). Chemical genetics reveals bacterial and host cell functions critical for type IV effector translocation by Legionella pneumophila. PLoS Pathog. 5, e1000501. doi: 10.1371/ journal.ppat.1000501
18. Clifton, D. R., Goss, R. A., Sahni, S. K., van Antwerp, D., Baggs, R. B., Marder, V. J., Silverman, D. J., and Sporn, L. A. (1998). NF-(B-dependent inhibition of apoptosis is essential for host cellsurvival during Rickettsia rickettsii infection. Proc. Natl. Acad. Sci. U.S.A. 95, 4646-4651.
19. Cohen, P. (2000). The regulation of protein function by multisite phosphorylation - a 25year update. Trends Biochem. Sci. 25, 596-601.
20. Covacci, A., Censini, S., Bugnoli, M., Petracca, R., Burroni, D., Macchia, G., Massone, A., Papini, E., Xiang, Z., Figura, N., and Rappuoli, R. (1993). Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc. Natl. Acad. Sci. U.S.A. 90, 5791-5795.
21. De Felipe, K. S., Glover, R. T., Charpentier, X., Anderson, O. R., Reyes, M., Pericone, C. D., and Shuman, H. A. (2008). Legionella eukaryotic-like type IV substrates interfere with organelle trafficking. PLoS Pathog. 4, e1000117. doi: 10.1371/journal.ppat.1000117
22. De Felipe, K. S., Pampou, S., Jovanovic, O. S., Pericone, C. D., Ye, S. F., Kalachikov, S., and Shuman, H. A. (2005). Evidence for acquisition of Legionella type IV secretion substrates via interdomain horizontal gene transfer. J. Bacteriol. 187, 7716-7726.
23. De Matteis, M. A., and Godi, A. (2004). PI-loting membrane traffic. Nat. Cell Biol. 6, 487-492.
24. Duronio, V. (2008). The life of a cell: apoptosis regulation by the PI3K/PKB pathway. Biochem. J. 415, 333-344.
25. Ensminger, A. W., and Isberg, R. R. (2010). E3 ubiquitin ligase activity and targeting of BAT3 by multiple Legionella pneumophila translocated substrates. Infect. Immun. 78, 3905-3919.
26. Farbrother, P., Wagner, C., Na, J., Tunggal, B., Morio, T., Urushihara, H., Tanaka, Y., Schleicher, M., Steinert, M., and Eichinger, L. (2006). Dictyostelium transcriptional host cell response upon infection with Legionella. Cell. Microbiol. 8, 438-456.
27. Fontana, M. F., Banga, S., Barry, K. C., Shen, X., Tan, Y., Luo, Z. Q., and Vance, R. E. (2011). Secreted bacterial effectors that inhibit host protein synthesis are critical for induction of the innate immune response to virulent Legionella pneumophila. PLoS Pathog. 7, e1001289. doi: 10.1371/journal. ppat.1001289
28. Fritz, J. H., Ferrero, R. L., Philpott, D. J., and Girardin, S. E. (2006). Nod-like proteins in immunity, inflammation and disease. Nat. Immunol. 7, 1250-1257.
29. Gaskins, C., Maeda, M., and Firtel, R. A. (1994). Identification and functional analysis of a developmentally regulated extracellular signal-regulated kinase gene in Dictyostelium discoideum. Mol. Cell Biol. 14, 6996-7012.
30. Ge, J., Xu, H., Li, T., Zhou, Y., Zhang, Z., Li, S., Liu, L., and Shao, F. (2009). A Legionella type IV effector activates the NF-κB pathway by phosphorylating the IκB family of inhibitors. Proc. Natl. Acad. Sci. U.S.A. 106, 13725-13730.
31. Hauck, C. R., Gulbins, E., Lang, F., and Meyer, T. F. (1999). Tyrosine phosphatase SHP-1 is involved in CD66-mediated phagocytosis of Opa52-expressing Neisseria gonorrhoeae. Infect. Immun. 67, 5490-5494.
32. Hayden, M. S., and Ghosh, S. (2008). Shared principles in NF-κB signaling. Cell 132, 344-362.
33. Hervet, E., Charpentier, X., Vianney, A., Lazzaroni, J. C., Gilbert, C., Atlan, D., and Doublet, P. (2011). The protein kinase LegK2 is a T4SS effector involved in endoplasmic reticulum recruitment and intracellular replication of Legionella pneumophila. Infect. Immun. doi: 10.1128/IAI.00805-10. [Epub ahead of print].
34. 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.
35. Horwitz, M. A. (1983b). The Legionnaires' disease bacterium (Legionella pneumophila) inhibits phagosome-lysosome fusion in human monocytes. J. Exp. Med. 158, 2108-2126.
36. 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.
37. Horwitz, M. A., and Maxfield, F. R. (1984). Legionella pneumophila inhibits acidification of its phagosome in human monocytes. J. Cell Biol. 99, 1936-1943.
38. Hsu, Y. M., Zhang, Y., You, Y., Wang, D., Li, H., Duramad, O., Qin, X. F., Dong, C., and Lin, X. (2007). The adaptor protein CARD9 is required for innate immune responses to intracellular pathogens. Nat. Immunol. 8, 198-205.
39. Huang, G., Shi, L. Z., and Chi, H. (2009). Regulation of JNK and p38 MAPK in the immune system: signal integration, propagation and termination. Cytokine 48, 161-169.
40. Huang, L., Boyd, D., Amyot, W. M., Hempstead, A. D., Luo, Z. Q., O'Connor, T. J., Chen, C., Machner, M., Montminy, T., and Isberg, R. R. (2010). The E Block motif is associated with Legionella pneumophila translocated substrates. Cell. Microbiol. 13, 227-245.
41. Ingmundson, A., Delprato, A., Lambright, D. G., and Roy, C. R. (2007). Legionella pneumophila proteins that regulate Rab1 membrane cycling. Nature 450, 365-369.
42. Ireton, K., Payrastre, B., Chap, H., Ogawa, W., Sakaue, H., Kasuga, M., and Cossart, P. (1996). A role for phosphoinositide 3-kinase in bacterial invasion. Science 274, 780-782.
43. 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.
44. 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.
45. Jeffrey, K. L., Camps, M., Rommel, C., and Mackay, C. R. (2007). Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat. Rev. Drug Discov. 6, 391-403.
46. Johnson, G. L., and Lapadat, R. (2002). Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 298, 1911-1912.
47. Karin, M., and Lin, A. (2002). NF-κB at the crossroads of life and death. Nat. Immunol. 3, 221-227.
48. Kawai, T., and Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on toll-like receptors. Nat. Immunol. 11, 373-384.
49. Khelef, N., Shuman, H. A., and Maxfield, F. R. (2001). Phagocytosis of wild-type Legionella pneumophila occurs through a wortmannin-insensitive pathway. Infect. Immun. 69, 5157-5161.
50. Krauss, M., and Haucke, V. (2007). Phosphoinositide-metabolizing enzymes at the interface between membrane traffic and cell signalling. EMBO Rep. 8, 241-246.
51. Kubori, T., Hyakutake, A., and Nagai, H. (2008). Legionella translocates an E3 ubiquitin ligase that has multiple U-boxes with distinct functions. Mol. Microbiol. 67, 1307-1319.
52. Kubori, T., Shinzawa, N., Kanuka, H., and Nagai, H. (2010). Legionella metaeffector exploits host proteasome to temporally regulate cognate effector. PLoS Pathog. 6, e1001216. doi: 10.1371/journal.ppat.1001216
53. Kwok, T., Zabler, D., Urman, S., Rohde, M., Hartig, R., Wessler, S., Misselwitz, R., Berger, J., Sewald, N., Konig, W., and Backert, S. (2007). Helicobacter exploits integrin for type IV secretion and kinase activation. Nature 449, 862-866.
54. Laguna, R. K., Creasey, E. A., Li, Z., Valtz, N., and Isberg, R. R. (2006). A Legionella pneumophila-translocated substrate that is required for growth within macrophages and protection from host cell death. Proc. Natl. Acad. Sci. U.S.A. 103, 18745-18750.
55. Lang, R., Hammer, M., and Mages, J. (2006). DUSP meet immunology: dual specificity MAPK phosphatases in control of the inflammatory response. J. Immunol. 177, 7497-7504.
56. Li, Z., Dugan, A. S., Bloomfield, G., Skelton, J., Ivens, A., Losick, V., and Isberg, R. R. (2009). The amoebal MAP kinase response to Legionella pneumophila is regulated by DupA. Cell Host Microbe 6, 253-267.
57. Lindmo, K., and Stenmark, H. (2006). Regulation of membrane traffic by phosphoinositide 3-kinases. J. Cell Sci. 119, 605-614.
58. Liu, Y., Shepherd, E. G., and Nelin, L. D. (2007). MAPK phosphatases - regulating the immune response. Nat. Rev. Immunol. 7, 202-212.
59. Losick, V. P., Haenssler, E., Moy, M. Y., and Isberg, R. R. (2010). LnaB: a Legionella pneumophila activator of NF-κB. Cell. Microbiol. 12, 1083-1097.
60. Losick, V. P., and Isberg, R. R. (2006). NF-κB translocation prevents host cell death after low-dose challenge by Legionella pneumophila. J. Exp. Med. 203, 2177-2189.
61. Lowe, M. (2005). Structure and function of the Lowe syndrome protein OCRL1. Traffic 6, 711-719.
62. Machner, M. P., and Isberg, R. R. (2007). A bifunctional bacterial protein links GDI displacement to Rab1 activation. Science 318, 974-977.
63. Manning, G., Plowman, G. D., Hunter, T., and Sudarsanam, S. (2002a). Evolution of protein kinase signaling from yeast to man. Trends Biochem. Sci. 27, 514-520.
64. Manning, G., Whyte, D. B., Martinez, R., Hunter, T., and Sudarsanam, S. (2002b). The protein kinase complement of the human genome. Science 298, 1912-1934.
65. Marra, A., Blander, S. J., Horwitz, M. A., and Shuman, H. A. (1992). Identification of a Legionella pneumophila locus required for intracellular multiplication in human macrophages. Proc. Natl. Acad. Sci. U.S.A. 89, 9607-9611.
66. Molina, M., Cid, V. J., and Martin, H. (2010). Fine regulation of Saccharomyces cerevisiae MAPK pathways by post-translational modifications. Yeast 27, 503-511.
67. Moorhead, G. B., De Wever, V., Templeton, G., and Kerk, D. (2009). Evolution of protein phosphatases in plants and animals. Biochem. J. 417, 401-409.
68. Mostowy, S., and Cossart, P. (2009). Cytoskeleton rearrangements during Listeria infection: clathrin and septins as new players in the game. Cell Motil. Cytoskeleton 66, 816-823.
69. Murata, T., Delprato, A., Ingmundson, A., Toomre, D. K., Lambright, D. G., and Roy, C. R. (2006). The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor. Nat. Cell Biol. 8, 971-977.
70. Nemeth, Z. H., Deitch, E. A., Davidson, M. T., Szabo, C., Vizi, E. S., and Hasko, G. (2004). Disruption of the actin cytoskeleton results in nuclear factor-κB activation and inflammatory mediator production in cultured human intestinal epithelial cells. J. Cell. Physiol. 200, 71-81.
71. Nolen, B., Taylor, S., and Ghosh, G. (2004). Regulation of protein kinases; controlling activity through activation segment conformation. Mol. Cell 15, 661-675.
72. Olsen, J. V., Blagoev, B., Gnad, F., Macek, B., Kumar, C., Mortensen, P., and Mann, M. (2006). Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 127, 635-648.
73. Patterson, K. I., Brummer, T., O'Brien, P. M., and Daly, R. J. (2009). Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem. J. 418, 475-489.
74. Peracino, B., Balest, A., and Bozzaro, S. (2010). Phosphoinositides differentially regulate bacterial uptake and Nramp1-induced resistance to Legionella infection in Dictyostelium. J. Cell Sci. 123, 4039-4051.
75. Philips, J. A. (2008). Mycobacterial manipulation of vacuolar sorting. Cell. Microbiol. 10, 2408-2415.
76. Pidoux, G., and Tasken, K. (2009). Specificity and spatial dynamics of protein kinase A signaling organized by A-kinase-anchoring proteins. J. Mol. Endocrinol. 44, 271-284.
77. Price, C. T., Al-Khodor, S., Al-Quadan, T., and Abu Kwaik, Y. (2010). Indispensable role for the eukaryotic-like ankyrin domains of the ankyrin B effector of Legionella pneumophila within macrophages and amoebae. Infect. Immun. 78, 2079-2088.
78. Pullikuth, A. K., and Catling, A. D. (2007). Scaffold mediated regulation of MAPK signaling and cytoskeletal dynamics: a perspective. Cell. Signal. 19, 1621-1632.
79. Ragaz, C., Pietsch, H., Urwyler, S., Tiaden, A., Weber, S. S., and Hilbi, H. (2008). The Legionella pneumophila phosphatidylinositol-4 phosphate-binding type IV substrate SidC recruits endoplasmic reticulum vesicles to a replication-permissive vacuole. Cell. Microbiol. 10, 2416-2433.
80. Ribet, D., and Cossart, P. (2010). Post-translational modifications in host cells during bacterial infection. FEBS Lett. 584, 2748-2758.
81. Ryan, K. R., and Shapiro, L. (2003). Temporal and spatial regulation in prokaryotic cell cycle progression and development. Annu. Rev. Biochem. 72, 367-394.
82. Schroder, M. (2008). Endoplasmic reticulum stress responses. Cell. Mol. Life Sci. 65, 862-894.
83. Scott, J. D., and Pawson, T. (2009). Cell signaling in space and time: where proteins come together and when they're apart. Science 326, 1220-1224.
84. Segal, E. D., Cha, J., Lo, J., Falkow, S., and Tompkins, L. S. (1999). Altered states: involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc. Natl. Acad. Sci. U.S.A. 96, 14559-14564.
85. Segal, E. D., Falkow, S., and Tompkins, L. S. (1996). Helicobacter pylori attachment to gastric cells induces cytoskeletal rearrangements and tyrosine phosphorylation of host cell proteins. Proc. Natl. Acad. Sci. U.S.A. 93, 1259-1264.
86. Segal, G., Purcell, M., and Shuman, H. A. (1998). Host cell killing and bacterial conjugation require overlapping sets of genes within a 22-kb region of the Legionella pneumophila genome. Proc. Natl. Acad. Sci. U.S.A. 95, 1669-1674.
87. Segall, J. E., Kuspa, A., Shaulsky, G., Ecke, M., Maeda, M., Gaskins, C., Firtel, R. A., and Loomis, W. F. (1995). A MAP kinase necessary for receptor-mediated activation of adenylyl cyclase in Dictyostelium. J. Cell Biol. 128, 405-413.
88. Shaw, M. H., Reimer, T., Kim, Y. G., and Nunez, G. (2008). NOD-like receptors (NLRs): bona fide intracellular microbial sensors. Curr. Opin. Immunol. 20, 377-382.
89. Shin, S., Case, C. L., Archer, K. A., Nogueira, C. V., Kobayashi, K. S., Flavell, R. A., Roy, C. R., and Zamboni, D. S. (2008). Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila. PLoS Pathog. 4, e1000220. doi: 10.1371/journal. ppat.1000220
90. Stein, M., Bagnoli, F., Halenbeck, R., Rappuoli, R., Fantl, W. J., and Covacci, A. (2002). c-Src/Lyn kinases activate Helicobacter pylori CagA through tyrosine phosphorylation of the EPIYA motifs. Mol. Microbiol. 43, 971-980.
91. Tachado, S. D., Samrakandi, M. M., and Cirillo, J. D. (2008). Non-opsonic phagocytosis of Legionella pneumophila by macrophages is mediated by phosphatidylinositol 3-kinase. PLoS ONE 3, e3324. doi: 10.1371/ journal.pone.0003324
92. Ting, J. P., Duncan, J. A., and Lei, Y. (2010). How the noninflammasome NLRs function in the innate immune system. Science 327, 286-290.
93. Toker, A., and Cantley, L. C. (1997). Signalling through the lipid products of phosphoinositide-3-OH kinase. Nature 387, 673-676.
94. Vergne, I., Chua, J., Lee, H. H., Lucas, M., Belisle, J., and Deretic, V. (2005). Mechanism of phagolysosome biogenesis block by viable Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 102, 4033-4038.
95. Viboud, G. I., and Bliska, J. B. (2005). Yersinia outer proteins: role in modulation of host cell signaling responses and pathogenesis. Annu. Rev. Microbiol. 59, 69-89.
96. Vogel, J. P., Andrews, H. L., Wong, S. K., and Isberg, R. R. (1998). Conjugative transfer by the virulence system of Legionella pneumophila. Science 279, 873-876.
97. Walburger, A., Koul, A., Ferrari, G., Nguyen, L., Prescianotto-Baschong, C., Huygen, K., Klebl, B., Thompson, C., Bacher, G., and Pieters, J. (2004). Protein kinase G from pathogenic mycobacteria promotes survival within macrophages. Science 304, 1800-1804.
98. Weber, S. S., Ragaz, C., and Hilbi, H. (2009a). Pathogen trafficking pathways and host phosphoinositide metabolism. Mol. Microbiol. 71, 1341-1352.
99. Weber, S. S., Ragaz, C., and Hilbi, H. (2009b). The inositol polyphosphate 5-phosphatase OCRL1 restricts intracellular growth of Legionella, localizes to the replicative vacuole and binds to the bacterial effector LpnE. Cell. Microbiol. 11, 442-460.
100. Weber, S. S., Ragaz, C., Reus, K., Nyfeler, Y., and Hilbi, H. (2006). Legionella pneumophila exploits PI(4)P to anchor secreted effector proteins to the replicative vacuole. PLoS Pathog. 2, e46. doi: 10.1371/journal.ppat.0020046
101. Welsh, C. T., Summersgill, J. T., and Miller, R. D. (2004). Increases in c-Jun N-terminal kinase/stress-activated protein kinase and p38 activity in monocyte-derived macrophages following the uptake of Legionella pneumophila. Infect. Immun. 72, 1512-1518.