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. 1995 May;63(5):1806–1809. doi: 10.1128/iai.63.5.1806-1809.1995

Differential susceptibility of yeast and hyphal forms of Candida albicans to macrophage-derived nitrogen-containing compounds.

E Blasi 1, L Pitzurra 1, M Puliti 1, A R Chimienti 1, R Mazzolla 1, R Barluzzi 1, F Bistoni 1
PMCID: PMC173228  PMID: 7729889

Abstract

Candida albicans is a dimorphic fungus capable of transition from the yeast form (Y-Candida) to the hyphal form (H-Candida). Both Y-Candida and H-Candida are known to be growth inhibited by murine macrophages (M phi) in vitro. In the present report, we demonstrate that M phi exposed to interferon gamma (IFN-gamma) plus lipopolysaccharide (LPS) show enhanced anti-Y-Candida and anti-H-Candida activities. To further investigate the phenomenon, Y-Candida and H-Candida were assessed for susceptibilities to M phi-derived supernatants. Only the growth of H-Candida, and not that of Y-Candida, is impaired by cell-free supernatants from M phi treated with IFN-gamma plus LPS. In contrast, no H-Candida growth inhibition occurs when supernatants from M phi exposed to IFN-gamma plus LPS in the presence of NG-monomethyl-L-arginine, an inhibitor of nitric oxide (NO) synthesis, are employed. Finally, supernatants from M phi incubated with sodium nitroprusside, an NO-generating agent, also show anti-H-Candida activity. In conclusion, these results indicate that H-Candida but not Y-Candida is susceptible to extracellular antifungal mechanisms employed by M phi, which likely involve stable nitrogen-containing compounds.

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Selected References

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  1. Adams L. B., Hibbs J. B., Jr, Taintor R. R., Krahenbuhl J. L. Microbiostatic effect of murine-activated macrophages for Toxoplasma gondii. Role for synthesis of inorganic nitrogen oxides from L-arginine. J Immunol. 1990 Apr 1;144(7):2725–2729. [PubMed] [Google Scholar]
  2. Araki S., Kagaya K., Kitoh K., Kimura M., Fukazawa Y. Enhancement of resistance to Escherichia coli infection in mice by dihydroheptaprenol, a synthetic polyprenol derivative. Infect Immun. 1987 Sep;55(9):2164–2170. doi: 10.1128/iai.55.9.2164-2170.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beno D. W., Mathews H. L. Growth inhibition of Candida albicans by interleukin-2-induced lymph node cells. Cell Immunol. 1990 Jun;128(1):89–100. doi: 10.1016/0008-8749(90)90009-g. [DOI] [PubMed] [Google Scholar]
  4. 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]
  5. Blasi E., Mazzolla R., Barluzzi R., Bistoni F. Microglial cell-mediated anti-Candida activity: temperature, ions, protein kinase C as crucial elements. J Neuroimmunol. 1991 Oct;34(1):53–60. doi: 10.1016/0165-5728(91)90098-r. [DOI] [PubMed] [Google Scholar]
  6. Blasi E., Pitzurra L., Puliti M., Lanfrancone L., Bistoni F. Early differential molecular response of a macrophage cell line to yeast and hyphal forms of Candida albicans. Infect Immun. 1992 Mar;60(3):832–837. doi: 10.1128/iai.60.3.832-837.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Blasi E., Puliti M., Pitzurra L., Barluzzi R., Mazzolla R., Adami C., Cox G. W., Bistoni F. Comparative studies on functional and secretory properties of macrophage cell lines derived from different anatomical sites. FEMS Immunol Med Microbiol. 1994 Sep;9(3):207–215. doi: 10.1111/j.1574-695X.1994.tb00495.x. [DOI] [PubMed] [Google Scholar]
  8. Bromberg Y., Pick E. Cyclic GMP metabolism in macrophages. I. Regulation of cyclic GMP levels by calcium and stimulation of cyclic GMP synthesis by NO-generating agents. Cell Immunol. 1980 Jun;52(1):73–83. doi: 10.1016/0008-8749(80)90401-3. [DOI] [PubMed] [Google Scholar]
  9. Cenci E., Romani L., Mencacci A., Spaccapelo R., Schiaffella E., Puccetti P., Bistoni F. Interleukin-4 and interleukin-10 inhibit nitric oxide-dependent macrophage killing of Candida albicans. Eur J Immunol. 1993 May;23(5):1034–1038. doi: 10.1002/eji.1830230508. [DOI] [PubMed] [Google Scholar]
  10. Diamond R. D., Krzesicki R., Jao W. Damage to pseudohyphal forms of Candida albicans by neutrophils in the absence of serum in vitro. J Clin Invest. 1978 Feb;61(2):349–359. doi: 10.1172/JCI108945. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
  12. Drapier J. C., Wietzerbin J., Hibbs J. B., Jr Interferon-gamma and tumor necrosis factor induce the L-arginine-dependent cytotoxic effector mechanism in murine macrophages. Eur J Immunol. 1988 Oct;18(10):1587–1592. doi: 10.1002/eji.1830181018. [DOI] [PubMed] [Google Scholar]
  13. Flesch I. E., Kaufmann S. H. Mechanisms involved in mycobacterial growth inhibition by gamma interferon-activated bone marrow macrophages: role of reactive nitrogen intermediates. Infect Immun. 1991 Sep;59(9):3213–3218. doi: 10.1128/iai.59.9.3213-3218.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Green L. C., Wagner D. A., Glogowski J., Skipper P. L., Wishnok J. S., Tannenbaum S. R. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem. 1982 Oct;126(1):131–138. doi: 10.1016/0003-2697(82)90118-x. [DOI] [PubMed] [Google Scholar]
  15. Green S. J., Meltzer M. S., Hibbs J. B., Jr, Nacy C. A. Activated macrophages destroy intracellular Leishmania major amastigotes by an L-arginine-dependent killing mechanism. J Immunol. 1990 Jan 1;144(1):278–283. [PubMed] [Google Scholar]
  16. Levitz S. M., Diamond R. D. A rapid colorimetric assay of fungal viability with the tetrazolium salt MTT. J Infect Dis. 1985 Nov;152(5):938–945. doi: 10.1093/infdis/152.5.938. [DOI] [PubMed] [Google Scholar]
  17. Liew F. Y., Millott S., Parkinson C., Palmer R. M., Moncada S. Macrophage killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol. 1990 Jun 15;144(12):4794–4797. [PubMed] [Google Scholar]
  18. Marletta M. A. Nitric oxide: biosynthesis and biological significance. Trends Biochem Sci. 1989 Dec;14(12):488–492. doi: 10.1016/0968-0004(89)90181-3. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Moncada S., Palmer R. M., Higgs E. A. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev. 1991 Jun;43(2):109–142. [PubMed] [Google Scholar]
  21. Nathan C. F., Hibbs J. B., Jr Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol. 1991 Feb;3(1):65–70. doi: 10.1016/0952-7915(91)90079-g. [DOI] [PubMed] [Google Scholar]
  22. Park J., Rikihisa Y. L-arginine-dependent killing of intracellular Ehrlichia risticii by macrophages treated with gamma interferon. Infect Immun. 1992 Sep;60(9):3504–3508. doi: 10.1128/iai.60.9.3504-3508.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Patterson-Delafield J., Martinez R. J., Lehrer R. I. Microbicidal cationic proteins in rabbit alveolar macrophages: a potential host defense mechanism. Infect Immun. 1980 Oct;30(1):180–192. doi: 10.1128/iai.30.1.180-192.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rockett K. A., Awburn M. M., Aggarwal B. B., Cowden W. B., Clark I. A. In vivo induction of nitrite and nitrate by tumor necrosis factor, lymphotoxin, and interleukin-1: possible roles in malaria. Infect Immun. 1992 Sep;60(9):3725–3730. doi: 10.1128/iai.60.9.3725-3730.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scaringi L., Blasi E., Cornacchione P., Bietta C., Bistoni F. A rapid Candida albicans hyphal-form growth inhibition assay: determination of myelomonocytic-mediated antifungal activity. Mycoses. 1991 Mar-Apr;34(3-4):119–123. doi: 10.1111/j.1439-0507.1991.tb00631.x. [DOI] [PubMed] [Google Scholar]
  26. Stamler J. S., Jaraki O., Osborne J., Simon D. I., Keaney J., Vita J., Singel D., Valeri C. R., Loscalzo J. Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin. Proc Natl Acad Sci U S A. 1992 Aug 15;89(16):7674–7677. doi: 10.1073/pnas.89.16.7674. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Stamler J. S., Singel D. J., Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science. 1992 Dec 18;258(5090):1898–1902. doi: 10.1126/science.1281928. [DOI] [PubMed] [Google Scholar]
  28. Vecchiarelli A., Dottorini M., Cociani C., Pietrella D., Todisco T., Bistoni F. Mechanism of intracellular candidacidal activity mediated by calcium ionophore in human alveolar macrophages. Am J Respir Cell Mol Biol. 1993 Jul;9(1):19–25. doi: 10.1165/ajrcmb/9.1.19. [DOI] [PubMed] [Google Scholar]
  29. Vecchiarelli A., Dottorini M., Puliti M., Todisco T., Cenci E., Bistoni F. Defective candidacidal activity of alveolar macrophages and peripheral blood monocytes from patients with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1991 May;143(5 Pt 1):1049–1054. doi: 10.1164/ajrccm/143.5_Pt_1.1049. [DOI] [PubMed] [Google Scholar]

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