Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia

Emmanuel Roilides, Isaac Kadiltsoglou, Anastasia Dimitriadou, Maria Hatzistilianou, Anna Manitsa, John Karpouzas, Philip A. Pizzo, Thomas J. Walsh

Research output: Contribution to journalArticlepeer-review

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°C for 2-4 days suppressed uptake of C. albicans blastoconidia in the presence of human serum (P ≤ 0.01), and anti-IL-4 inhibited its suppressive effect. The effect of IL-4 was protein synthesis-dependent. Interferon-γ (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-γ, GM-CSF and M-CSF appear to counteract suppression of morphonuclear leukocyte phagocytic activity suggesting new approaches to the management of disseminated candidiasis.

Original languageEnglish (US)
Pages (from-to)169-180
Number of pages12
JournalFEMS Immunology and Medical Microbiology
Volume19
Issue number2
DOIs
StatePublished - Oct 1997

Keywords

  • Candida
  • Cytokine
  • Interleukin-4
  • Monocyte/macrophage
  • Uptake

ASJC Scopus subject areas

  • Immunology and Allergy
  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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