Abstract
To elucidate the role of the oxidative burst in macrophage resistance to Legionella infection, we examined a murine macrophage-like cell line, J774.1, for permissiveness to Legionella growth, using a mutant that has a selective defect in the oxidative burst after lipopolysaccharide (LPS) stimulation. Legionella pneumophila serogroup 1 was infected into J774.1 monolayers, and then the extent of bacterial growth was estimated by a CFU assay. Both the parental cell line, JA-4, and the LPS-resistant mutant, LPS1916, were permissive for Legionella growth but became nonpermissive after pretreatment with gamma interferon. However, pretreatment of LPS1916 cells with LPS failed to inhibit bacterial growth, although LPS-treated JA-4 cells exhibited inhibited multiplication of the bacteria. The bacterial growth inhibition in JA-4 and mutant LPS1916 cells was correlated with the extent of the oxidative burst in the cells, as judged by cytochrome c reduction but not nitrite production. Neither transferrin receptor expression nor the iron content in JA-4 and LPS1916 cells, with or without LPS treatment, was correlated with suppression of Legionella growth. These results suggest that the restriction of Legionella growth in J774.1 cells is due to a bactericidal effect of the oxidative burst rather than reduction of the iron supply to the intracellular bacteria and that the effectors are reactive oxygen intermediates and not reactive nitrogen intermediates.
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- Amano F., Akamatsu Y. A lipopolysaccharide (LPS)-resistant mutant isolated from a macrophagelike cell line, J774.1, exhibits an altered activated-macrophage phenotype in response to LPS. Infect Immun. 1991 Jun;59(6):2166–2174. doi: 10.1128/iai.59.6.2166-2174.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Byrd T. F., Horwitz M. A. Interferon gamma-activated human monocytes downregulate transferrin receptors and inhibit the intracellular multiplication of Legionella pneumophila by limiting the availability of iron. J Clin Invest. 1989 May;83(5):1457–1465. doi: 10.1172/JCI114038. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Byrd T. F., Horwitz M. A. Regulation of transferrin receptor expression and ferritin content in human mononuclear phagocytes. Coordinate upregulation by iron transferrin and downregulation by interferon gamma. J Clin Invest. 1993 Mar;91(3):969–976. doi: 10.1172/JCI116318. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davis G. S., Winn W. C., Jr, Gump D. W., Beaty H. N. The kinetics of early inflammatory events during experimental pneumonia due to Legionella pneumophila in guinea pigs. J Infect Dis. 1983 Nov;148(5):823–835. doi: 10.1093/infdis/148.5.823. [DOI] [PubMed] [Google Scholar]
- Fujio H., Yoshida S., Miyamoto H., Mitsuyama M., Mizuguchi Y. Investigation of the role of macrophages and endogenous interferon-gamma in natural resistance of mice against Legionella pneumophila infection. FEMS Microbiol Immunol. 1992 Apr;4(4):183–191. doi: 10.1111/j.1574-6968.1992.tb04993.x. [DOI] [PubMed] [Google Scholar]
- Goldberg M., Belkowski L. S., Bloom B. R. Regulation of macrophage function by interferon-gamma. Somatic cell genetic approaches in murine macrophage cell lines to mechanisms of growth inhibition, the oxidative burst, and expression of the chronic granulomatous disease gene. J Clin Invest. 1990 Feb;85(2):563–569. doi: 10.1172/JCI114473. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacobs R. F., Locksley R. M., Wilson C. B., Haas J. E., Klebanoff S. J. Interaction of primate alveolar macrophages and Legionella pneumophila. J Clin Invest. 1984 Jun;73(6):1515–1523. doi: 10.1172/JCI111357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jepras R. I., Fitzgeorge R. B. The effect of oxygen-dependent antimicrobial systems on strains of Legionella pneumophila of different virulence. J Hyg (Lond) 1986 Aug;97(1):61–69. doi: 10.1017/s0022172400064354. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Katz S. M., Hashemi S. Electron microscopic examination of the inflammatory response to Legionella pneumophila in guinea pigs. Lab Invest. 1982 Jan;46(1):24–32. [PubMed] [Google Scholar]
- Klein T. W., Yamamoto Y., Brown H. K., Friedman H. Interferon-gamma induced resistance to Legionella pneumophila in susceptible A/J mouse macrophages. J Leukoc Biol. 1991 Jan;49(1):98–103. doi: 10.1002/jlb.49.1.98. [DOI] [PubMed] [Google Scholar]
- Lochner J. E., Friedman R. L., Bigley R. H., Iglewski B. H. Effect of oxygen-dependent antimicrobial systems on Legionella pneumophila. Infect Immun. 1983 Jan;39(1):487–489. doi: 10.1128/iai.39.1.487-489.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Locksley R. M., Jacobs R. F., Wilson C. B., Weaver W. M., Klebanoff S. J. Susceptibility of Legionella pneumophila to oxygen-dependent microbicidal systems. J Immunol. 1982 Nov;129(5):2192–2197. [PubMed] [Google Scholar]
- Matsiota-Bernard P., Léfèbre C., Sedqui M., Cornillet P., Guenounou M. Involvement of tumor necrosis factor alpha in intracellular multiplication of Legionella pneumophila in human monocytes. Infect Immun. 1993 Dec;61(12):4980–4983. doi: 10.1128/iai.61.12.4980-4983.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Summersgill J. T., Powell L. A., Buster B. L., Miller R. D., Ramirez J. A. Killing of Legionella pneumophila by nitric oxide in gamma-interferon-activated macrophages. J Leukoc Biol. 1992 Dec;52(6):625–629. doi: 10.1002/jlb.52.6.625. [DOI] [PubMed] [Google Scholar]
- Takema M., Inaba K., Uno K., Kakihara K., Tawara K., Muramatsu S. Effect of L-arginine on the retention of macrophage tumoricidal activity. J Immunol. 1991 Mar 15;146(6):1928–1933. [PubMed] [Google Scholar]
- Yamamoto Y., Klein T. W., Brown K., Friedman H. Differential morphologic and metabolic alterations in permissive versus nonpermissive murine macrophages infected with Legionella pneumophila. Infect Immun. 1992 Aug;60(8):3231–3237. doi: 10.1128/iai.60.8.3231-3237.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto Y., Klein T. W., Newton C. A., Widen R., Friedman H. Growth of Legionella pneumophila in thioglycolate-elicited peritoneal macrophages from A/J mice. Infect Immun. 1988 Feb;56(2):370–375. doi: 10.1128/iai.56.2.370-375.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]