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°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.

Cytokines and fungal infections

“…IL‐4 is one of the cytokines associated with the development of Th2 response against fungal pathogens. It also suppresses phagocytic activity of monocytes/macrophages against C. albicans (Cenci et al , 1993; Roilides et al , 1997a). IL‐4 was shown to impair host resistance to A. fumigatus , H. capsulatum , C. neoformans and Paracoccidioides braziliensis in animal models (Cenci et al , 1999; Kawakami et al , 1999a; Gildea et al , 2003; Pina et al , 2004).…”

Combating Fungal Infections

“…It also suppresses phagocytic activity of monocytes/macrophages against C. albicans (Cenci et al 1993;Roilides et al 1997). It also suppresses phagocytic activity of monocytes/macrophages against C. albicans (Cenci et al 1993;Roilides et al 1997).…”