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. 1990 Apr;58(4):1073–1077. doi: 10.1128/iai.58.4.1073-1077.1990

Augmentation of GG2EE macrophage cell line-mediated anti-Candida activity by gamma interferon, tumor necrosis factor, and interleukin-1.

E Blasi 1, S Farinelli 1, L Varesio 1, F Bistoni 1
PMCID: PMC258584  PMID: 2108087

Abstract

The expression of anti-Candida activity in the GG2EE macrophage cell line, generated by immortalization of fresh bone marrow with v-raf and v-myc oncogenes, was studied. GG2EE cells spontaneously inhibited the growth of an agerminative mutant of Candida albicans in vitro. The anti-Candida activity was maximal after 8 h of coculture and was proportional to the effector-to-target ratio. Gamma interferon (IFN-gamma), interleukin-1 (IL-1), and tumor necrosis factor (TNF) all significantly enhanced the anti-Candida activity of GG2EE cells. In contrast, IL-3, IL-4, and colony-stimulating factor 1 were ineffective. The augmentation of anti-Candida activity was not always concomitant with enhancement of phagocytosis, since IFN-gamma and colony-stimulating factor 1, but not IL-1 or TNF, augmented the phagocytic ability of GG2EE cells. Furthermore, the augmentation of anti-Candida activity in GG2EE cells did not correlate with the acquisition of antitumor activity. In fact, none of the cytokines alone were able to induce antitumor activity in GG2EE cells, which, however, could be activated to a tumoricidal stage by IFN-gamma plus heat-killed Listeria monocytogenes. These findings demonstrate that GG2EE cells exhibit spontaneous anti-Candida activity and that such activity is enhanced by TNF, IL-1, and IFN-gamma.

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Selected References

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  1. Arai T., Mikami Y., Yokoyama K. Phagocytosis of Candida albicans by rabbit alveolar macrophages and guinea pig neutrophils. Sabouraudia. 1977 Jul;15(2):171–177. [PubMed] [Google Scholar]
  2. Baccarini M., Bistoni F., Puccetti P., Garaci E. Natural cell-mediated cytotoxicity against Candida albicans induced by cyclophosphamide: nature of the in vitro cytotoxic effector. Infect Immun. 1983 Oct;42(1):1–9. doi: 10.1128/iai.42.1.1-9.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baccarini M., Blasi E., Puccetti P., Bistoni F. Phagocytic killing of Candida albicans by different murine effector cells. Sabouraudia. 1983 Dec;21(4):271–286. [PubMed] [Google Scholar]
  4. Bach M. C., Sahyoun A., Adler J. L., Schlesinger R. M., Breman J., Madras P., P'eng F., Monaco A. P. High incidence of fungus infections in renal transplantation patients treated with antilymphocyte and conventional immunosuppression. Transplant Proc. 1973 Mar;5(1):549–553. [PubMed] [Google Scholar]
  5. Bistoni F., Baccarini M., Blasi E., Puccetti P., Marconi P. A radiolabel release microassay for phagocytic killing of Candida albicans. J Immunol Methods. 1982 Aug 13;52(3):369–377. doi: 10.1016/0022-1759(82)90008-4. [DOI] [PubMed] [Google Scholar]
  6. Bistoni F., Vecchiarelli A., Cenci E., Puccetti P., Marconi P., Cassone A. Evidence for macrophage-mediated protection against lethal Candida albicans infection. Infect Immun. 1986 Feb;51(2):668–674. doi: 10.1128/iai.51.2.668-674.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blasi E., Mathieson B. J., Varesio L., Cleveland J. L., Borchert P. A., Rapp U. R. Selective immortalization of murine macrophages from fresh bone marrow by a raf/myc recombinant murine retrovirus. Nature. 1985 Dec 19;318(6047):667–670. doi: 10.1038/318667a0. [DOI] [PubMed] [Google Scholar]
  8. Blasi E., Radzioch D., Durum S. K., Varesio L. A murine macrophage cell line, immortalized by v-raf and v-myc oncogenes, exhibits normal macrophage functions. Eur J Immunol. 1987 Oct;17(10):1491–1498. doi: 10.1002/eji.1830171016. [DOI] [PubMed] [Google Scholar]
  9. Brummer E., Morrison C. J., Stevens D. A. Recombinant and natural gamma-interferon activation of macrophages in vitro: different dose requirements for induction of killing activity against phagocytizable and nonphagocytizable fungi. Infect Immun. 1985 Sep;49(3):724–730. doi: 10.1128/iai.49.3.724-730.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brummer E., Stevens D. A. Activation of pulmonary macrophages for fungicidal activity by gamma-interferon or lymphokines. Clin Exp Immunol. 1987 Dec;70(3):520–528. [PMC free article] [PubMed] [Google Scholar]
  11. Cheers C., Hill M., Haigh A. M., Stanley E. R. Stimulation of macrophage phagocytic but not bactericidal activity by colony-stimulating factor 1. Infect Immun. 1989 May;57(5):1512–1516. doi: 10.1128/iai.57.5.1512-1516.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Cho S. Y., Choi H. Y. Opportunistic fungal infection among cancer patients. A ten-year autopsy study. Am J Clin Pathol. 1979 Oct;72(4):617–621. doi: 10.1093/ajcp/72.4.617. [DOI] [PubMed] [Google Scholar]
  13. Diamond R. D., Clark R. A., Haudenschild C. C. Damage to Candida albicans hyphae and pseudohyphae by the myeloperoxidase system and oxidative products of neutrophil metabolism in vitro. J Clin Invest. 1980 Nov;66(5):908–917. doi: 10.1172/JCI109958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Diamond R. D., Haudenschild C. C. Monocyte-mediated serum-independent damage to hyphal and pseudohyphal forms of Candida albicans in vitro. J Clin Invest. 1981 Jan;67(1):173–182. doi: 10.1172/JCI110010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Evron R. In vitro phagocytosis of Candida albicans by peritoneal mouse macrophages. Infect Immun. 1980 Jun;28(3):963–971. doi: 10.1128/iai.28.3.963-971.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hurtrel B., Lagrange P. H., Michel J. C. Systemic candidiasis in mice. II.--Main role of polymorphonuclear leukocytes in resistance to infection. Ann Immunol (Paris) 1980 Jan-Feb;131C(1):105–118. [PubMed] [Google Scholar]
  18. Jones J. M. Granulomatous hepatitis due to Candida albicans in patients with acute leukemia. Ann Intern Med. 1981 Apr;94(4 Pt 1):475–477. doi: 10.7326/0003-4819-94-4-475. [DOI] [PubMed] [Google Scholar]
  19. Karbassi A., Becker J. M., Foster J. S., Moore R. N. Enhanced killing of Candida albicans by murine macrophages treated with macrophage colony-stimulating factor: evidence for augmented expression of mannose receptors. J Immunol. 1987 Jul 15;139(2):417–421. [PubMed] [Google Scholar]
  20. Klein R. S., Harris C. A., Small C. B., Moll B., Lesser M., Friedland G. H. Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N Engl J Med. 1984 Aug 9;311(6):354–358. doi: 10.1056/NEJM198408093110602. [DOI] [PubMed] [Google Scholar]
  21. Lehrer R. I., Ferrari L. G., Patterson-Delafield J., Sorrell T. Fungicidal activity of rabbit alveolar and peritoneal macrophages against Candida albicans. Infect Immun. 1980 Jun;28(3):1001–1008. doi: 10.1128/iai.28.3.1001-1008.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mattia E., Carruba G., Angiolella L., Cassone A. Induction of germ tube formation by N-acetyl-D-glucosamine in Candida albicans: uptake of inducer and germinative response. J Bacteriol. 1982 Nov;152(2):555–562. doi: 10.1128/jb.152.2.555-562.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mildvan D., Mathur U., Enlow R. W., Romain P. L., Winchester R. J., Colp C., Singman H., Adelsberg B. R., Spigland I. Opportunistic infections and immune deficiency in homosexual men. Ann Intern Med. 1982 Jun;96(6 Pt 1):700–704. doi: 10.7326/0003-4819-96-6-700. [DOI] [PubMed] [Google Scholar]
  24. Ozato K., Uesaka I. The role of macrophages in Candida albicans infection in vitro. Jpn J Microbiol. 1974 Jan;18(1):29–35. doi: 10.1111/j.1348-0421.1974.tb00740.x. [DOI] [PubMed] [Google Scholar]
  25. Ruco L. P., Meltzer M. S. Defective tumoricidal capacity of macrophages from C3H/HeJ mice. J Immunol. 1978 Jan;120(1):329–334. [PubMed] [Google Scholar]
  26. Sasada M., Johnston R. B., Jr Macrophage microbicidal activity. Correlation between phagocytosis-associated oxidative metabolism and the killing of Candida by macrophages. J Exp Med. 1980 Jul 1;152(1):85–98. doi: 10.1084/jem.152.1.85. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Schuit K. E. Phagocytosis and intracellular killing of pathogenic yeasts by human monocytes and neutrophils. Infect Immun. 1979 Jun;24(3):932–938. doi: 10.1128/iai.24.3.932-938.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Stanley V. C., Hurley R. The growth of Candida species in cultures of mouse peritoneal macrophages. J Pathol. 1969 Feb;97(2):357–366. doi: 10.1002/path.1710970222. [DOI] [PubMed] [Google Scholar]
  29. Vecchiarelli A., Bistoni F., Cenci E., Perito S., Cassone A. In-vitro killing of Candida species by murine immunoeffectors and its relationship to the experimental pathogenicity. Sabouraudia. 1985 Oct;23(5):377–387. doi: 10.1080/00362178585380541. [DOI] [PubMed] [Google Scholar]

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