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Infect Immun. 1990 May; 58(5): 1201–1209.
PMCID: PMC258610

Growth inhibition of Cryptococcus neoformans by cultured human monocytes: role of the capsule, opsonins, the culture surface, and cytokines.


Despite a presumed critical role of macrophages in the host response to cryptococcal infections, previous studies have failed to show growth inhibition of encapsulated Cryptococcus neoformans by human peripheral blood cultured monocyte-derived macrophages (MO-M phi). Here, we examined whether MO-M phi could be induced to inhibit growth of an encapsulated strain and an isogenic acapsular mutant strain of C. neoformans. MO-M phi were cultured in microwells, and inhibition was measured by comparing CFU at 0 and 24 h after fungal challenge. MO-M phi cultured on plastic surfaces failed to inhibit growth of the encapsulated strain, even in the presence of pooled human serum and/or anticapsular antibody. Moreover, the presence of anticapsular antibody significantly enhanced fungal growth. However, if MO-M phi were cultured on surfaces coated with fibronectin or poly-L-lysine (but not laminin or collagen) and yeast cells were opsonized with pooled human serum, then complete growth inhibition occurred. Preincubation with various concentrations of tumor necrosis factor, granulocyte macrophage colony-stimulating factor, 1,25-dihydroxycholecalciferol, or supernatants from C. neoformans-stimulated lymphocytes failed to activate macrophages for enhanced antifungal activity. The addition of gamma interferon resulted in a significant loss of growth inhibition. For the acapsular strain, complete growth inhibition was observed regardless of the choice of culture surface, opsonins, or cytokines. Fungicidal activity, as measured by a significant decrement in CFU compared with the initial inoculum, was not observed under any conditions tested. These data demonstrate that macrophages are capable of inhibiting cryptococcal growth but that this capacity is markedly influenced by the culture surface, opsonins, cytokines, and the fungal capsule.

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  • Bermudez LE, Young LS. Tumor necrosis factor, alone or in combination with IL-2, but not IFN-gamma, is associated with macrophage killing of Mycobacterium avium complex. J Immunol. 1988 May 1;140(9):3006–3013. [PubMed]
  • Bohnsack JF, Kleinman HK, Takahashi T, O'Shea JJ, Brown EJ. Connective tissue proteins and phagocytic cell function. Laminin enhances complement and Fc-mediated phagocytosis by cultured human macrophages. J Exp Med. 1985 May 1;161(5):912–923. [PMC free article] [PubMed]
  • Brown EJ. The role of extracellular matrix proteins in the control of phagocytosis. J Leukoc Biol. 1986 May;39(5):579–591. [PubMed]
  • Brown EJ, Goodwin JL. Fibronectin receptors of phagocytes. Characterization of the Arg-Gly-Asp binding proteins of human monocytes and polymorphonuclear leukocytes. J Exp Med. 1988 Mar 1;167(3):777–793. [PMC free article] [PubMed]
  • Cohen DA, Stotelmyer NL, Kaplan AM. Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals. Exp Cell Res. 1985 Apr;157(2):511–519. [PubMed]
  • Crowle AJ, Ross EJ, May MH. Inhibition by 1,25(OH)2-vitamin D3 of the multiplication of virulent tubercle bacilli in cultured human macrophages. Infect Immun. 1987 Dec;55(12):2945–2950. [PMC free article] [PubMed]
  • Davies SF, Clifford DP, Hoidal JR, Repine JE. Opsonic requirements for the uptake of Cryptococcus neoformans by human polymorphonuclear leukocytes and monocytes. J Infect Dis. 1982 Jun;145(6):870–874. [PubMed]
  • Diamond RD, Allison AC. Nature of the effector cells responsible for antibody-dependent cell-mediated killing of Cryptococcus neoformans. Infect Immun. 1976 Sep;14(3):716–720. [PMC free article] [PubMed]
  • Diamond RD, Bennett JE. Growth of Cryptococcus neoformans within human macrophages in vitro. Infect Immun. 1973 Feb;7(2):231–236. [PMC free article] [PubMed]
  • Diamond RD, Bennett JE. Prognostic factors in cryptococcal meningitis. A study in 111 cases. Ann Intern Med. 1974 Feb;80(2):176–181. [PubMed]
  • Diamond RD, May JE, Kane MA, Frank MM, Bennett JE. The role of the classical and alternate complement pathways in host defenses against Cryptococcus neoformans infection. J Immunol. 1974 Jun;112(6):2260–2270. [PubMed]
  • Douvas GS, Looker DL, Vatter AE, Crowle AJ. Gamma interferon activates human macrophages to become tumoricidal and leishmanicidal but enhances replication of macrophage-associated mycobacteria. Infect Immun. 1985 Oct;50(1):1–8. [PMC free article] [PubMed]
  • Dromer F, Charreire J, Contrepois A, Carbon C, Yeni P. Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect Immun. 1987 Mar;55(3):749–752. [PMC free article] [PubMed]
  • Flesch IE, Schwamberger G, Kaufmann SH. Fungicidal activity of IFN-gamma-activated macrophages. Extracellular killing of Cryptococcus neoformans. J Immunol. 1989 May 1;142(9):3219–3224. [PubMed]
  • Fromtling RA, Shadomy HJ, Jacobson ES. Decreased virulence in stable, acapsular mutants of cryptococcus neoformans. Mycopathologia. 1982 Jul 23;79(1):23–29. [PubMed]
  • Gentry LO, Remington JS. Resistance against Cryptococcus conferred by intracellular bacteria and protozoa. J Infect Dis. 1971 Jan;123(1):22–31. [PubMed]
  • Granger DL, Hibbs JB, Jr, Perfect JR, Durack DT. Specific amino acid (L-arginine) requirement for the microbiostatic activity of murine macrophages. J Clin Invest. 1988 Apr;81(4):1129–1136. [PMC free article] [PubMed]
  • Granger DL, Perfect JR, Durack DT. Virulence of Cryptococcus neoformans. Regulation of capsule synthesis by carbon dioxide. J Clin Invest. 1985 Aug;76(2):508–516. [PMC free article] [PubMed]
  • Granger DL, Perfect JR, Durack DT. Macrophage-mediated fungistasis in vitro: requirements for intracellular and extracellular cytotoxicity. J Immunol. 1986 Jan;136(2):672–680. [PubMed]
  • HOWARD DH. Some factors which affect the initiation of growth of Cryptococcus neoformans. J Bacteriol. 1961 Sep;82:430–435. [PMC free article] [PubMed]
  • Jacobson ES, Ayers DJ, Harrell AC, Nicholas CC. Genetic and phenotypic characterization of capsule mutants of Cryptococcus neoformans. J Bacteriol. 1982 Jun;150(3):1292–1296. [PMC free article] [PubMed]
  • Kaplan G, Gaudernack G. In vitro differentiation of human monocytes. Differences in monocyte phenotypes induced by cultivation on glass or on collagen. J Exp Med. 1982 Oct 1;156(4):1101–1114. [PMC free article] [PubMed]
  • Kitz DJ, Johnson CR, Kobayashi GS, Medoff G, Little JR. Growth inhibition of Cryptococcus neoformans by cloned cultured murine macrophages. Cell Immunol. 1984 Oct 15;88(2):489–500. [PubMed]
  • Kozel TR, Follette JL. Opsonization of encapsulated Cryptococcus neoformans by specific anticapsular antibody. Infect Immun. 1981 Mar;31(3):978–984. [PMC free article] [PubMed]
  • Kozel TR, Highison B, Stratton CJ. Localization on encapsulated Cryptococcus neoformans of serum components opsonic for phagocytosis by macrophages and neutrophils. Infect Immun. 1984 Feb;43(2):574–579. [PMC free article] [PubMed]
  • Kwon-Chung KJ, Polacheck I, Popkin TJ. Melanin-lacking mutants of Cryptococcus neoformans and their virulence for mice. J Bacteriol. 1982 Jun;150(3):1414–1421. [PMC free article] [PubMed]
  • Lane HC, Fauci AS. Immunologic reconstitution in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Nov;103(5):714–718. [PubMed]
  • Levitz SM, DiBenedetto DJ. Differential stimulation of murine resident peritoneal cells by selectively opsonized encapsulated and acapsular Cryptococcus neoformans. Infect Immun. 1988 Oct;56(10):2544–2551. [PMC free article] [PubMed]
  • Levitz SM, DiBenedetto DJ. Paradoxical role of capsule in murine bronchoalveolar macrophage-mediated killing of Cryptococcus neoformans. J Immunol. 1989 Jan 15;142(2):659–665. [PubMed]
  • Levitz SM, DiBenedetto DJ, Diamond RD. A rapid fluorescent assay to distinguish attached from phagocytized yeast particles. J Immunol Methods. 1987 Jul 16;101(1):37–42. [PubMed]
  • Lo SK, Ryan TJ, Gilboa N, Lai L, Malik AB. Role of catalytic and lysine-binding sites in plasmin-induced neutrophil adherence to endothelium. J Clin Invest. 1989 Sep;84(3):793–801. [PMC free article] [PubMed]
  • Mantovani B, Rabinovitch M, Nussenzweig V. Phagocytosis of immune complexes by macrophages. Different roles of the macrophage receptor sites for complement (C3) and for immunoglobulin (IgG). J Exp Med. 1972 Apr 1;135(4):780–792. [PMC free article] [PubMed]
  • McDonald JA. Extracellular matrix assembly. Annu Rev Cell Biol. 1988;4:183–207. [PubMed]
  • Miller GP, Kohl S. Antibody-dependent leukocyte killing of Cryptococcus neoformans. J Immunol. 1983 Sep;131(3):1455–1459. [PubMed]
  • Miller GP, Puck J. In vitro human lymphocyte responses to Cryptococcus neoformans. Evidence for primary and secondary responses in normals and infected subjects. J Immunol. 1984 Jul;133(1):166–172. [PubMed]
  • Monga DP. Role of macrophages in resistance of mice to experimental cryptococcosis. Infect Immun. 1981 Jun;32(3):975–978. [PMC free article] [PubMed]
  • Murphy JW, McDaniel DO. In vitro reactivity of natural killer (NK) cells against Cryptococcus neoformans. J Immunol. 1982 Apr;128(4):1577–1583. [PubMed]
  • Murray HW. Interferon-gamma, the activated macrophage, and host defense against microbial challenge. Ann Intern Med. 1988 Apr;108(4):595–608. [PubMed]
  • Murray HW, Hillman JK, Rubin BY, Kelly CD, Jacobs JL, Tyler LW, Donelly DM, Carriero SM, Godbold JH, Roberts RB. Patients at risk for AIDS-related opportunistic infections. Clinical manifestations and impaired gamma interferon production. N Engl J Med. 1985 Dec 12;313(24):1504–1510. [PubMed]
  • Nabavi N, Murphy JW. Antibody-dependent natural killer cell-mediated growth inhibition of Cryptococcus neoformans. Infect Immun. 1986 Feb;51(2):556–562. [PMC free article] [PubMed]
  • Nathan CF, Prendergast TJ, Wiebe ME, Stanley ER, Platzer E, Remold HG, Welte K, Rubin BY, Murray HW. Activation of human macrophages. Comparison of other cytokines with interferon-gamma. J Exp Med. 1984 Aug 1;160(2):600–605. [PMC free article] [PubMed]
  • Proctor RA, Textor JA, Vann JM, Mosher DF. Role of fibronectin in human monocyte and macrophage bactericidal activity. Infect Immun. 1985 Mar;47(3):629–637. [PMC free article] [PubMed]
  • Supino R, Gibelli N, Zunino F. Induction of differentiation of Friend murine erythroleukemia cells by poly-L-lysine and daunorubicin-poly-L-lysine conjugate. J Natl Cancer Inst. 1986 Aug;77(2):453–457. [PubMed]
  • Takada Y, Wayner EA, Carter WG, Hemler ME. Extracellular matrix receptors, ECMRII and ECMRI, for collagen and fibronectin correspond to VLA-2 and VLA-3 in the VLA family of heterodimers. J Cell Biochem. 1988 Aug;37(4):385–393. [PubMed]
  • Weinberg PB, Becker S, Granger DL, Koren HS. Growth inhibition of Cryptococcus neoformans by human alveolar macrophages. Am Rev Respir Dis. 1987 Nov;136(5):1242–1247. [PubMed]
  • Wright SD. Cellular strategies in receptor-mediated phagocytosis. Rev Infect Dis. 1985 May-Jun;7(3):395–397. [PubMed]
  • Wright SD. Methods for the study of receptor-mediated phagocytosis. Methods Enzymol. 1986;132:204–221. [PubMed]
  • Wright SD, Craigmyle LS, Silverstein SC. Fibronectin and serum amyloid P component stimulate C3b- and C3bi-mediated phagocytosis in cultured human monocytes. J Exp Med. 1983 Oct 1;158(4):1338–1343. [PMC free article] [PubMed]
  • Wright SD, Silverstein SC. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J Exp Med. 1983 Dec 1;158(6):2016–2023. [PMC free article] [PubMed]

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