TY - JOUR
T1 - Interleukin-4 suppresses antifungal activity of human mononuclear phagocytes against Candida albicans in association with decreased uptake of blastoconidia
AU - Roilides, Emmanuel
AU - Kadiltsoglou, Isaac
AU - Dimitriadou, Anastasia
AU - Hatzistilianou, Maria
AU - Manitsa, Anna
AU - Karpouzas, John
AU - Pizzo, Philip A.
AU - Walsh, Thomas J.
PY - 1997/10
Y1 - 1997/10
N2 - 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.
AB - 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.
KW - Candida
KW - Cytokine
KW - Interleukin-4
KW - Monocyte/macrophage
KW - Uptake
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UR - http://www.scopus.com/inward/citedby.url?scp=0030684042&partnerID=8YFLogxK
U2 - 10.1016/S0928-8244(97)00083-7
DO - 10.1016/S0928-8244(97)00083-7
M3 - Article
C2 - 9395062
AN - SCOPUS:0030684042
SN - 0928-8244
VL - 19
SP - 169
EP - 180
JO - FEMS Immunology and Medical Microbiology
JF - FEMS Immunology and Medical Microbiology
IS - 2
ER -