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. 1996 Oct;64(10):4381–4384. doi: 10.1128/iai.64.10.4381-4384.1996

Infection of macrophage-like cells by Legionella species that have not been associated with disease.

W A O'Connell 1, L Dhand 1, N P Cianciotto 1
PMCID: PMC174385  PMID: 8926117

Abstract

We assessed the ability of Legionella species that have not been associated with disease to infect macrophage-like U937 cells. Two of fourteen species tested exhibited a 50% infective dose that was within I log unit of that of virulent L. pneumophila. Indeed, intracellular CFU of L. jamestowniensis and L. parisiensis increased 100-fold over a 72-h period. These data indicate that additional legionellae can flourish within phagocytes and therefore, can, if given the opportunity, cause disease.

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Selected References

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  1. Abu Kwaik Y., Eisenstein B. I., Engleberg N. C. Phenotypic modulation by Legionella pneumophila upon infection of macrophages. Infect Immun. 1993 Apr;61(4):1320–1329. doi: 10.1128/iai.61.4.1320-1329.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benson R. F., Thacker W. L., Fang F. C., Kanter B., Mayberry W. R., Brenner D. J. Legionella sainthelensi serogroup 2 isolated from patients with pneumonia. Res Microbiol. 1990 May;141(4):453–463. doi: 10.1016/0923-2508(90)90071-w. [DOI] [PubMed] [Google Scholar]
  3. Benson R. F., Thacker W. L., Lanser J. A., Sangster N., Mayberry W. R., Brenner D. J. Legionella adelaidensis, a new species isolated from cooling tower water. J Clin Microbiol. 1991 May;29(5):1004–1006. doi: 10.1128/jcm.29.5.1004-1006.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berger K. H., Isberg R. R. Two distinct defects in intracellular growth complemented by a single genetic locus in Legionella pneumophila. Mol Microbiol. 1993 Jan;7(1):7–19. doi: 10.1111/j.1365-2958.1993.tb01092.x. [DOI] [PubMed] [Google Scholar]
  5. Bornstein N., Marmet D., Surgot M., Nowicki M., Meugnier H., Fleurette J., Ageron E., Grimont F., Grimont P. A., Thacker W. L. Legionella gratiana sp. nov. isolated from French spa water. Res Microbiol. 1989 Oct;140(8):541–552. doi: 10.1016/0923-2508(89)90086-7. [DOI] [PubMed] [Google Scholar]
  6. Bornstein N., Mercatello A., Marmet D., Surgot M., Deveaux Y., Fleurette J. Pleural infection caused by Legionella anisa. J Clin Microbiol. 1989 Sep;27(9):2100–2101. doi: 10.1128/jcm.27.9.2100-2101.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Brenner D. J., Steigerwalt A. G., McDade J. E. Classification of the Legionnaires' disease bacterium: Legionella pneumophila, genus novum, species nova, of the family Legionellaceae, familia nova. Ann Intern Med. 1979 Apr;90(4):656–658. doi: 10.7326/0003-4819-90-4-656. [DOI] [PubMed] [Google Scholar]
  8. Campbell J., Bibb W. F., Lambert M. A., Eng S., Steigerwalt A. G., Allard J., Moss C. W., Brenner D. J. Legionella sainthelensi: a new species of Legionella isolated from water near Mt. St. Helens. Appl Environ Microbiol. 1984 Feb;47(2):369–373. doi: 10.1128/aem.47.2.369-373.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Catrenich C. E., Johnson W. Characterization of the selective inhibition of growth of virulent Legionella pneumophila by supplemented Mueller-Hinton medium. Infect Immun. 1989 Jun;57(6):1862–1864. doi: 10.1128/iai.57.6.1862-1864.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cianciotto N. P., Eisenstein B. I., Mody C. H., Toews G. B., Engleberg N. C. A Legionella pneumophila gene encoding a species-specific surface protein potentiates initiation of intracellular infection. Infect Immun. 1989 Apr;57(4):1255–1262. doi: 10.1128/iai.57.4.1255-1262.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cianciotto N., Eisenstein B. I., Engleberg N. C., Shuman H. Genetics and molecular pathogenesis of Legionella pneumophila, an intracellular parasite of macrophages. Mol Biol Med. 1989 Oct;6(5):409–424. [PubMed] [Google Scholar]
  12. Dennis P. J., Brenner D. J., Thacker W. L., Wait R., Vesey G., Steigerwalt A. G., Benson R. F. Five new Legionella species isolated from water. Int J Syst Bacteriol. 1993 Apr;43(2):329–337. doi: 10.1099/00207713-43-2-329. [DOI] [PubMed] [Google Scholar]
  13. Dowling J. N., Saha A. K., Glew R. H. Virulence factors of the family Legionellaceae. Microbiol Rev. 1992 Mar;56(1):32–60. doi: 10.1128/mr.56.1.32-60.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Edelstein P. H., Brenner D. J., Moss C. W., Steigerwalt A. G., Francis E. M., George W. L. Legionella wadsworthii species nova: a cause of human pneumonia. Ann Intern Med. 1982 Dec;97(6):809–813. doi: 10.7326/0003-4819-97-6-809. [DOI] [PubMed] [Google Scholar]
  15. Edelstein P. H. Comparative study of selective media for isolation of Legionella pneumophila from potable water. J Clin Microbiol. 1982 Oct;16(4):697–699. doi: 10.1128/jcm.16.4.697-699.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Eitrem R., Forsgren A., Nilsson C. Pneumonia and acute pancreatitis most probably caused by a Legionella longbeachae infection. Scand J Infect Dis. 1987;19(3):381–382. doi: 10.3109/00365548709018486. [DOI] [PubMed] [Google Scholar]
  17. Fallon R. J., Rowbotham T. J. Microbiological investigations into an outbreak of Pontiac fever due to Legionella micdadei associated with use of a whirlpool. J Clin Pathol. 1990 Jun;43(6):479–483. doi: 10.1136/jcp.43.6.479. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fang G. D., Yu V. L., Vickers R. M. Disease due to the Legionellaceae (other than Legionella pneumophila). Historical, microbiological, clinical, and epidemiological review. Medicine (Baltimore) 1989 Mar;68(2):116–132. doi: 10.1097/00005792-198903000-00005. [DOI] [PubMed] [Google Scholar]
  19. Fenstersheib M. D., Miller M., Diggins C., Liska S., Detwiler L., Werner S. B., Lindquist D., Thacker W. L., Benson R. F. Outbreak of Pontiac fever due to Legionella anisa. Lancet. 1990 Jul 7;336(8706):35–37. doi: 10.1016/0140-6736(90)91532-f. [DOI] [PubMed] [Google Scholar]
  20. Fields B. S., Barbaree J. M., Sanden G. N., Morrill W. E. Virulence of a Legionella anisa strain associated with Pontiac fever: an evaluation using protozoan, cell culture, and guinea pig models. Infect Immun. 1990 Sep;58(9):3139–3142. doi: 10.1128/iai.58.9.3139-3142.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fields B. S., Barbaree J. M., Shotts E. B., Jr, Feeley J. C., Morrill W. E., Sanden G. N., Dykstra M. J. Comparison of guinea pig and protozoan models for determining virulence of Legionella species. Infect Immun. 1986 Sep;53(3):553–559. doi: 10.1128/iai.53.3.553-559.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Griffith M. E., Lindquist D. S., Benson R. F., Thacker W. L., Brenner D. J., Wilkinson H. W. First isolation of Legionella gormanii from human disease. J Clin Microbiol. 1988 Feb;26(2):380–381. doi: 10.1128/jcm.26.2.380-381.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Halberstam M., Isenberg H. D., Hilton E. Abscess and empyema caused by Legionella micdadei. J Clin Microbiol. 1992 Feb;30(2):512–513. doi: 10.1128/jcm.30.2.512-513.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Harris P., Ralph P. Human leukemic models of myelomonocytic development: a review of the HL-60 and U937 cell lines. J Leukoc Biol. 1985 Apr;37(4):407–422. doi: 10.1002/jlb.37.4.407. [DOI] [PubMed] [Google Scholar]
  25. Herwaldt L. A., Gorman G. W., McGrath T., Toma S., Brake B., Hightower A. W., Jones J., Reingold A. L., Boxer P. A., Tang P. W. A new Legionella species, Legionella feeleii species nova, causes Pontiac fever in an automobile plant. Ann Intern Med. 1984 Mar;100(3):333–338. doi: 10.7326/0003-4819-100-3-333. [DOI] [PubMed] [Google Scholar]
  26. Horwitz M. A. Interactions between macrophages and Legionella pneumophila. Curr Top Microbiol Immunol. 1992;181:265–282. doi: 10.1007/978-3-642-77377-8_10. [DOI] [PubMed] [Google Scholar]
  27. Husmann L. K., Johnson W. Adherence of Legionella pneumophila to guinea pig peritoneal macrophages, J774 mouse macrophages, and undifferentiated U937 human monocytes: role of Fc and complement receptors. Infect Immun. 1992 Dec;60(12):5212–5218. doi: 10.1128/iai.60.12.5212-5218.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kilborn J. A., Manz L. A., O'Brien M., Douglass M. C., Horst H. M., Kupin W., Fisher E. J. Necrotizing cellulitis caused by Legionella micdadei. Am J Med. 1992 Jan;92(1):104–106. doi: 10.1016/0002-9343(92)90024-6. [DOI] [PubMed] [Google Scholar]
  29. King C. H., Fields B. S., Shotts E. B., Jr, White E. H. Effects of cytochalasin D and methylamine on intracellular growth of Legionella pneumophila in amoebae and human monocyte-like cells. Infect Immun. 1991 Mar;59(3):758–763. doi: 10.1128/iai.59.3.758-763.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lee J. V., West A. A. Survival and growth of Legionella species in the environment. Soc Appl Bacteriol Symp Ser. 1991;20:121S–129S. [PubMed] [Google Scholar]
  31. Levi M. H., Pasculle A. W., Dowling J. N. Role of the alveolar macrophage in host defense and immunity to Legionella micdadei pneumonia in the guinea pig. Microb Pathog. 1987 Apr;2(4):269–282. doi: 10.1016/0882-4010(87)90125-2. [DOI] [PubMed] [Google Scholar]
  32. Marston B. J., Lipman H. B., Breiman R. F. Surveillance for Legionnaires' disease. Risk factors for morbidity and mortality. Arch Intern Med. 1994 Nov 14;154(21):2417–2422. [PubMed] [Google Scholar]
  33. McKinney R. M., Porschen R. K., Edelstein P. H., Bissett M. L., Harris P. P., Bondell S. P., Steigerwalt A. G., Weaver R. E., Ein M. E., Lindquist D. S. Legionella longbeachae species nova, another etiologic agent of human pneumonia. Ann Intern Med. 1981 Jun;94(6):739–743. doi: 10.7326/0003-4819-94-6-739. [DOI] [PubMed] [Google Scholar]
  34. Moffat J. F., Tompkins L. S. A quantitative model of intracellular growth of Legionella pneumophila in Acanthamoeba castellanii. Infect Immun. 1992 Jan;60(1):296–301. doi: 10.1128/iai.60.1.296-301.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. O'Connell W. A., Bangsborg J. M., Cianciotto N. P. Characterization of a Legionella micdadei mip mutant. Infect Immun. 1995 Aug;63(8):2840–2845. doi: 10.1128/iai.63.8.2840-2845.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. O'Connell W. A., Hickey E. K., Cianciotto N. P. A Legionella pneumophila gene that promotes hemin binding. Infect Immun. 1996 Mar;64(3):842–848. doi: 10.1128/iai.64.3.842-848.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Orrison L. H., Cherry W. B., Tyndall R. L., Fliermans C. B., Gough S. B., Lambert M. A., McDougal L. K., Bibb W. F., Brenner D. J. Legionella oakridgensis: unusual new species isolated from cooling tower water. Appl Environ Microbiol. 1983 Feb;45(2):536–545. doi: 10.1128/aem.45.2.536-545.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Park D., Pugliese A., Cunha B. A. Legionella micdadei prosthetic valve endocarditis. Infection. 1994 May-Jun;22(3):213–215. doi: 10.1007/BF01716708. [DOI] [PubMed] [Google Scholar]
  39. Pearlman E., Jiwa A. H., Engleberg N. C., Eisenstein B. I. Growth of Legionella pneumophila in a human macrophage-like (U937) cell line. Microb Pathog. 1988 Aug;5(2):87–95. doi: 10.1016/0882-4010(88)90011-3. [DOI] [PubMed] [Google Scholar]
  40. Pope C. D., O'Connell W., Cianciotto N. P. Legionella pneumophila mutants that are defective for iron acquisition and assimilation and intracellular infection. Infect Immun. 1996 Feb;64(2):629–636. doi: 10.1128/iai.64.2.629-636.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Rodgers F. G., Gibson F. C., 3rd Opsonin-independent adherence and intracellular development of Legionella pneumophila within U-937 cells. Can J Microbiol. 1993 Jul;39(7):718–722. doi: 10.1139/m93-103. [DOI] [PubMed] [Google Scholar]
  42. Rowbotham T. J. Current views on the relationships between amoebae, legionellae and man. Isr J Med Sci. 1986 Sep;22(9):678–689. [PubMed] [Google Scholar]
  43. Sadosky A. B., Wiater L. A., Shuman H. A. Identification of Legionella pneumophila genes required for growth within and killing of human macrophages. Infect Immun. 1993 Dec;61(12):5361–5373. doi: 10.1128/iai.61.12.5361-5373.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sanden G. N., Morrill W. E., Fields B. S., Breiman R. F., Barbaree J. M. Incubation of water samples containing amoebae improves detection of legionellae by the culture method. Appl Environ Microbiol. 1992 Jun;58(6):2001–2004. doi: 10.1128/aem.58.6.2001-2004.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Steele T. W., McLennan A. M. Infection of Tetrahymena pyriformis by Legionella longbeachae and other Legionella species found in potting mixes. Appl Environ Microbiol. 1996 Mar;62(3):1081–1083. doi: 10.1128/aem.62.3.1081-1083.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tang P. W., Toma S., MacMillan L. G. Legionella oakridgensis: laboratory diagnosis of a human infection. J Clin Microbiol. 1985 Mar;21(3):462–463. doi: 10.1128/jcm.21.3.462-463.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Thacker W. L., Benson R. F., Schifman R. B., Pugh E., Steigerwalt A. G., Mayberry W. R., Brenner D. J., Wilkinson H. W. Legionella tucsonensis sp. nov. isolated from a renal transplant recipient. J Clin Microbiol. 1989 Aug;27(8):1831–1834. doi: 10.1128/jcm.27.8.1831-1834.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Thacker W. L., Benson R. F., Staneck J. L., Vincent S. R., Mayberry W. R., Brenner D. J., Wilkinson H. W. Legionella cincinnatiensis sp. nov. isolated from a patient with pneumonia. J Clin Microbiol. 1988 Mar;26(3):418–420. doi: 10.1128/jcm.26.3.418-420.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Thacker W. L., Dyke J. W., Benson R. F., Havlichek D. H., Jr, Robinson-Dunn B., Stiefel H., Schneider W., Moss C. W., Mayberry W. R., Brenner D. J. Legionella lansingensis sp. nov. isolated from a patient with pneumonia and underlying chronic lymphocytic leukemia. J Clin Microbiol. 1992 Sep;30(9):2398–2401. doi: 10.1128/jcm.30.9.2398-2401.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Wadowsky R. M., Wilson T. M., Kapp N. J., West A. J., Kuchta J. M., States S. J., Dowling J. N., Yee R. B. Multiplication of Legionella spp. in tap water containing Hartmannella vermiformis. Appl Environ Microbiol. 1991 Jul;57(7):1950–1955. doi: 10.1128/aem.57.7.1950-1955.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Wilkinson H. W., Drasar V., Thacker W. L., Benson R. F., Schindler J., Potuznikova B., Mayberry W. R., Brenner D. J. Legionella moravica sp. nov. and Legionella brunensis sp. nov. isolated from cooling-tower water. Ann Inst Pasteur Microbiol. 1988 Jul-Aug;139(4):393–402. doi: 10.1016/0769-2609(88)90102-0. [DOI] [PubMed] [Google Scholar]
  52. Wilkinson H. W., Thacker W. L., Benson R. F., Polt S. S., Brookings E., Mayberry W. R., Brenner D. J., Gilley R. G., Kirklin J. K. Legionella birminghamensis sp. nov. isolated from a cardiac transplant recipient. J Clin Microbiol. 1987 Nov;25(11):2120–2122. doi: 10.1128/jcm.25.11.2120-2122.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Winn W. C., Jr Legionnaires disease: historical perspective. Clin Microbiol Rev. 1988 Jan;1(1):60–81. doi: 10.1128/cmr.1.1.60. [DOI] [PMC free article] [PubMed] [Google Scholar]

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