title: Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia.
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.
authors.affiliation: Department of Pediatrics, University of Thessaloniki, Greece.
authors.forename: E
authors.initials: E
authors.lastname: Roilides
authors.forename: I
authors.initials: I
authors.lastname: Kadiltsoglou
authors.forename: A
authors.initials: A
authors.lastname: Dimitriadou
authors.forename: M
authors.initials: M
authors.lastname: Hatzistilianou
authors.forename: A
authors.initials: A
authors.lastname: Manitsa
authors.forename: J
authors.initials: J
authors.lastname: Karpouzas
authors.forename: P A
authors.initials: PA
authors.lastname: Pizzo
authors.forename: T J
authors.initials: TJ
authors.lastname: Walsh
mesh_terms: D000328:Adult; D002176:Candida albicans / Q000276:immunology*; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D010586:Phagocytes; D011956:Receptors, Cell Surface / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
chemical_list: D037181:Lectins, C-Type; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D011956:Receptors, Cell Surface; D013481:Superoxides; D015847:Interleukin-4; D003513:Cycloheximide