Interleukin-4 Suppresses Antifungal Activity of Human Mononuclear Phagocytes Against Candida Albicans in Association With Decreased Uptake of Blastoconidia

FEMS Immunol Med Microbiol. 1997 Oct;19(2):169-80. doi: 10.1111/j.1574-695X.1997.tb01086.x.

Abstract

Pathogenesis of invasive candidiasis may involve regulatory activities of Th2 immunity on phagocytic host defenses. The effects of interleukin (IL)-4 on antifungal capacity of human mononuclear phagocytes against Candida albicans were studied. Incubation of adherent mononuclear leukocytes from healthy donors with IL-4 (1-5 ng ml(-1)) at 37 degrees C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P < or = 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-gamma (0.25-25 ng ml(-1)), granulocyte-macrophage colony-stimulating factor (CSF, 20 ng ml(-1)), macrophage-CSF (15 ng ml(-1)) but not IL-10 (100 ng ml(-1)) somewhat counteracted the suppressive effect of IL-4. In contrast, mannose receptor-mediated uptake of blastoconidia in the absence of serum was increased by IL-4. Killing of conidia was decreased after incubation of morphonuclear leukocytes with IL-4 for 2 days (P < 0.05). While superoxide anion production in response to phorbol myristate acetate was decreased by IL-4 (P < 0.05), it was not altered in response to blastoconidia and pseudohyphae. Morphonuclear leukocyte-induced pseudohyphal damage also remained unaltered. These findings suggest that IL-4 plays its detrimental role in invasive candidiasis by predominantly suppressing uptake and killing of blastoconidia by morphonuclear leukocytes. Anti-IL-4, IFN-gamma, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.

MeSH terms

  • Adult
  • Candida albicans / immunology*
  • Cycloheximide / pharmacology
  • Humans
  • Interleukin-4 / pharmacology*
  • Lectins, C-Type*
  • Mannose-Binding Lectins*
  • Monocytes / drug effects*
  • Monocytes / immunology
  • Monocytes / microbiology
  • Phagocytes
  • Receptors, Cell Surface / physiology
  • Superoxides / metabolism

Substances

  • Lectins, C-Type
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • mannose receptor
  • Superoxides
  • Interleukin-4
  • Cycloheximide