The Journal of Immunology, Vol 137, Issue 9 2980-2984, Copyright © 1986 by American Association of Immunologists

ARTICLES

Growth inhibition of Candida albicans by human polymorphonuclear neutrophils: activation by interferon-gamma and tumor necrosis factor

JY Djeu, DK Blanchard, D Halkias and H Friedman

This study was designed to determine whether anti-fungal activity in human polymorphonuclear neutrophils (PMN) might be under the regulation of cytokines such as tumor necrosis factor (TNF) and interferon-gamma (IFN-gamma). By using a radiolabel microassay developed in our laboratory that makes use of the incorporation of [3H]glucose into residual candida, we demonstrated that PMN were better able to inhibit Candida albicans growth in vitro than peripheral blood lymphocytes (PBL). PMN from normal volunteers added to C. albicans for 24 hr at 37 degrees C in a 96-well microplate inhibited fungal growth almost completely at the 300:1 effector/target ratio and frequently at 100:1. Significant activity was still detected at 10:1. In contrast, PBL from the same donors had less activity than PMN at all the ratios tested and lost all function at the 30:1 ratio. TNF and IFN-gamma added to the PMN/candida cultures additionally enhanced PMN to inhibit candida growth. Both cytokines effectively activated PMN down to 0.1 to 0.01 U/ml, and neither cytokine interfered directly with fungal growth, even up to 1000 U/ml. Concentrations of TNF and IFN-gamma below the level that enhanced PMN function when added together to PMN acted synergistically to significantly enhance their anti-fungal activity. Therefore, TNF and IFN-gamma which are active on lymphoid cells, also appear to have the ability to directly activate PMN, and the synergistic action of the two cytokines at low doses that may be below the toxic range may prove to be of clinical importance in protection of immunocompromised host against opportunistic infections.

This article has been cited by other articles:

				A. Mullick, M. Elias, P. Harakidas, A. Marcil, M. Whiteway, B. Ge, T. J. Hudson, A. W. Caron, L. Bourget, S. Picard, et al. Gene Expression in HL60 Granulocytoids and Human Polymorphonuclear Leukocytes Exposed to Candida albicans{dagger} Infect. Immun., January 1, 2004; 72(1): 414 - 429. [Abstract] [Full Text] [PDF]

				M. Rouabhia, G. Ross, N. Page, and J. Chakir Interleukin-18 and Gamma Interferon Production by Oral Epithelial Cells in Response to Exposure to Candida albicans or Lipopolysaccharide Stimulation Infect. Immun., December 1, 2002; 70(12): 7073 - 7080. [Abstract] [Full Text] [PDF]

				J. Brieland, D. Essig, C. Jackson, D. Frank, D. Loebenberg, F. Menzel, B. Arnold, B. DiDomenico, and R. Hare Comparison of Pathogenesis and Host Immune Responses to Candida glabrata and Candida albicans in Systemically Infected Immunocompetent Mice Infect. Immun., August 1, 2001; 69(8): 5046 - 5055. [Abstract] [Full Text] [PDF]

				M. G. Netea, L. J. H. van Tits, J. H. A. J. Curfs, F. Amiot, J. F. G. M. Meis, J. W. M. van der Meer, and B. J. Kullberg Increased Susceptibility of TNF-{alpha} Lymphotoxin-{alpha} Double Knockout Mice to Systemic Candidiasis Through Impaired Recruitment of Neutrophils and Phagocytosis of Candida albicans J. Immunol., August 1, 1999; 163(3): 1498 - 1505. [Abstract] [Full Text] [PDF]

				E. Roilides, A. Dimitriadou-Georgiadou, T. Sein, I. Kadiltsoglou, and T. J. Walsh Tumor Necrosis Factor Alpha Enhances Antifungal Activities of Polymorphonuclear and Mononuclear Phagocytes against Aspergillus fumigatus Infect. Immun., December 1, 1998; 66(12): 5999 - 6003. [Abstract] [Full Text] [PDF]

				C. Scully, M. EI-Kabir, and L. P. Samaranayake Candida and Oral Candidosis: A Review Critical Reviews in Oral Biology & Medicine, January 1, 1994; 5(2): 125 - 157. [Abstract] [Full Text] [PDF]

				C. Smith, T Davis, D Anderson, L Solam, M. Beckmann, R Jerzy, S. Dower, D Cosman, and R. Goodwin A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins Science, May 25, 1990; 248(4958): 1019 - 1023. [Abstract] [PDF]