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. 1988 May;56(5):1187–1193. doi: 10.1128/iai.56.5.1187-1193.1988

Role of gamma interferon in induction of natural killer activity by Legionella pneumophila in vitro and in an experimental murine infection model.

D K Blanchard 1, H Friedman 1, W E Stewart 2nd 1, T W Klein 1, J Y Djeu 1
PMCID: PMC259782  PMID: 3128479

Abstract

Legionella pneumophila has been shown to induce gamma interferon (IFN-gamma) both in vitro and in vivo during experimental infections of mice. With complement-mediated serologic depletion of murine splenocytes, the cellular sources of IFN-gamma following in vitro stimulation with L. pneumophila antigens were Thy-1.2+, Lyt-2-, L3T4-, and asialo-GM1+, which is consistent with the natural killer (NK) cell phenotype. Additionally, Percoll density discontinuous centrifugation demonstrated that maximal production of IFN coincided with high NK activity in fractions which were enriched for large granular lymphocytes. Furthermore, 18- to 24-h incubation of splenocytes with L. pneumophila whole-cell vaccine resulted in augmented NK cytotoxic activity against YAC-1 tumor target cells in a 51Cr release assay. The addition of macrophages to purified large granular lymphocyte populations augmented both IFN-gamma production and NK activity, suggesting that antigen is required for optimal responses. In an experimental infection model using an intratracheal inoculation route, NK activity was enhanced in the spleen, peripheral blood, and lung cells of infected mice, with maximal stimulation in the lung leukocytes at the site of infection. The results of the present study indicate that NK cells respond in vivo and in vitro to stimulation by L. pneumophila by producing IFN-gamma and by increased cytolytic activity.

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Selected References

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  1. Abo T., Sugawara S., Amenomori A., Itoh H., Rikiishi H., Moro I., Kumagai K. Selective phagocytosis of gram-positive bacteria and interleukin 1-like factor production by a subpopulation of large granular lymphocytes. J Immunol. 1986 May 1;136(9):3189–3197. [PubMed] [Google Scholar]
  2. Bhardwaj N., Nash T. W., Horwitz M. A. Interferon-gamma-activated human monocytes inhibit the intracellular multiplication of Legionella pneumophila. J Immunol. 1986 Oct 15;137(8):2662–2669. [PubMed] [Google Scholar]
  3. Blanchard D. K., Djeu J. Y., Klein T. W., Friedman H., Stewart W. E., 2nd Induction of tumor necrosis factor by Legionella pneumophila. Infect Immun. 1987 Feb;55(2):433–437. doi: 10.1128/iai.55.2.433-437.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blanchard D. K., Djeu J. Y., Klein T. W., Friedman H., Stewart W. E., 2nd Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages. J Immunol. 1986 Feb 1;136(3):963–970. [PubMed] [Google Scholar]
  5. Blanchard D. K., Klein T. W., Friedman H., Stewart W. E., 2nd Kinetics and characterization of interferon production by murine spleen cells stimulated with Legionella pneumophila antigens. Infect Immun. 1985 Sep;49(3):719–723. doi: 10.1128/iai.49.3.719-723.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blanchard D. K., Stewart W. E., 2nd, Klein T. W., Friedman H., Djeu J. Y. Cytolytic activity of human peripheral blood leukocytes against Legionella pneumophila-infected monocytes: characterization of the effector cell and augmentation by interleukin 2. J Immunol. 1987 Jul 15;139(2):551–556. [PubMed] [Google Scholar]
  7. Chmielarczyk W., Kirchner H., Ernst R., Storch E. Attempts to correlate interferon induction and activation of natural killer cells by Corynebacterium parvum. Immunobiology. 1985 May;169(4):403–411. doi: 10.1016/S0171-2985(85)80020-6. [DOI] [PubMed] [Google Scholar]
  8. Claeys H., Van Damme J., De Ley M., Vermylen C., Billiau A. Activation of natural cytotoxicity of human peripheral blood mononuclear cells by interferon: a kinetic study and comparison of different interferon types. Br J Haematol. 1982 Jan;50(1):85–94. doi: 10.1111/j.1365-2141.1982.tb01893.x. [DOI] [PubMed] [Google Scholar]
  9. Dialynas D. P., Wilde D. B., Marrack P., Pierres A., Wall K. A., Havran W., Otten G., Loken M. R., Pierres M., Kappler J. Characterization of the murine antigenic determinant, designated L3T4a, recognized by monoclonal antibody GK1.5: expression of L3T4a by functional T cell clones appears to correlate primarily with class II MHC antigen-reactivity. Immunol Rev. 1983;74:29–56. doi: 10.1111/j.1600-065x.1983.tb01083.x. [DOI] [PubMed] [Google Scholar]
  10. Djeu J. Y., Blanchard D. K., Halkias D., Friedman H. Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor. J Immunol. 1986 Nov 1;137(9):2980–2984. [PubMed] [Google Scholar]
  11. Fertsch D., Vogel S. N. Recombinant interferons increase macrophage Fc receptor capacity. J Immunol. 1984 May;132(5):2436–2439. [PubMed] [Google Scholar]
  12. Handa K., Suzuki R., Matsui H., Shimizu Y., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). II. IL 2-induced interferon gamma production. J Immunol. 1983 Feb;130(2):988–992. [PubMed] [Google Scholar]
  13. Holmberg L. A., Ault K. A. Characterization of Listeria monocytogenes-induced murine natural killer cells. Immunol Res. 1986;5(1):50–60. doi: 10.1007/BF02917194. [DOI] [PubMed] [Google Scholar]
  14. Horwitz M. A., Silverstein S. C. 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. 1981 Feb 1;153(2):386–397. doi: 10.1084/jem.153.2.386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Horwitz M. A., Silverstein S. C. 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. 1981 Feb 1;153(2):398–406. doi: 10.1084/jem.153.2.398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Itoh K., Tilden A. B., Kumagai K., Balch C. M. Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells. J Immunol. 1985 Feb;134(2):802–807. [PubMed] [Google Scholar]
  17. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  18. Kasahara T., Djeu J. Y., Dougherty S. F., Oppenheim J. J. Capacity of human large granular lymphocytes (LGL) to produce multiple lymphokines: interleukin 2, interferon, and colony stimulating factor. J Immunol. 1983 Nov;131(5):2379–2385. [PubMed] [Google Scholar]
  19. Kasai M., Iwamori M., Nagai Y., Okumura K., Tada T. A glycolipid on the surface of mouse natural killer cells. Eur J Immunol. 1980 Mar;10(3):175–180. doi: 10.1002/eji.1830100304. [DOI] [PubMed] [Google Scholar]
  20. Klebanoff S. J., Vadas M. A., Harlan J. M., Sparks L. H., Gamble J. R., Agosti J. M., Waltersdorph A. M. Stimulation of neutrophils by tumor necrosis factor. J Immunol. 1986 Jun 1;136(11):4220–4225. [PubMed] [Google Scholar]
  21. Klimpel G. R., Niesel D. W., Klimpel K. D. Natural cytotoxic effector cell activity against Shigella flexneri-infected HeLa cells. J Immunol. 1986 Feb 1;136(3):1081–1086. [PubMed] [Google Scholar]
  22. McDade J. E., Shepard C. C., Fraser D. W., Tsai T. R., Redus M. A., Dowdle W. R. Legionnaires' disease: isolation of a bacterium and demonstration of its role in other respiratory disease. N Engl J Med. 1977 Dec 1;297(22):1197–1203. doi: 10.1056/NEJM197712012972202. [DOI] [PubMed] [Google Scholar]
  23. Milisauskas V. K., Cudkowicz G., Nakamura I. Suppression of murine NK activity induced by Corynebacterium parvum: further characterization and abrogation of suppressor cells. Cancer Immunol Immunother. 1986;21(1):51–57. doi: 10.1007/BF00199377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Natuk R. J., Welsh R. M. Accumulation and chemotaxis of natural killer/large granular lymphocytes at sites of virus replication. J Immunol. 1987 Feb 1;138(3):877–883. [PubMed] [Google Scholar]
  25. Rager-Zisman B., Bloom B. R. Interferons and natural killer cells. Br Med Bull. 1985 Jan;41(1):22–27. doi: 10.1093/oxfordjournals.bmb.a072018. [DOI] [PubMed] [Google Scholar]
  26. Shalaby M. R., Aggarwal B. B., Rinderknecht E., Svedersky L. P., Finkle B. S., Palladino M. A., Jr Activation of human polymorphonuclear neutrophil functions by interferon-gamma and tumor necrosis factors. J Immunol. 1985 Sep;135(3):2069–2073. [PubMed] [Google Scholar]
  27. Stein-Streilein J., Guffee J. In vivo treatment of mice and hamsters with antibodies to asialo GM1 increases morbidity and mortality to pulmonary influenza infection. J Immunol. 1986 Feb 15;136(4):1435–1441. [PubMed] [Google Scholar]
  28. Svedersky L. P., Benton C. V., Berger W. H., Rinderknecht E., Harkins R. N., Palladino M. A. Biological and antigenic similarities of murine interferon-gamma and macrophage-activating factor. J Exp Med. 1984 Mar 1;159(3):812–827. doi: 10.1084/jem.159.3.812. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Tarkkanen J., Saxén H., Nurminen M., Mäkelä P. H., Saksela E. Bacterial induction of human activated lymphocyte killing and its inhibition by lipopolysaccharide (LPS). J Immunol. 1986 Apr 1;136(7):2662–2669. [PubMed] [Google Scholar]
  30. Virelizier J. L., Perez N., Arenzana-Seisdedos F., Devos R. Pure interferon gamma enhances class II HLA antigens on human monocyte cell lines. Eur J Immunol. 1984 Jan;14(1):106–108. doi: 10.1002/eji.1830140120. [DOI] [PubMed] [Google Scholar]
  31. Welsh R. M. Natural killer cells and interferon. Crit Rev Immunol. 1984;5(1):55–93. [PubMed] [Google Scholar]
  32. Wiltrout R. H., Herberman R. B., Zhang S. R., Chirigos M. A., Ortaldo J. R., Green K. M., Jr, Talmadge J. E. Role of organ-associated NK cells in decreased formation of experimental metastases in lung and liver. J Immunol. 1985 Jun;134(6):4267–4275. [PubMed] [Google Scholar]

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