The in vitro effects of interferon-gamma, alone or in combination with amphotericin B, tested against the pathogenic fungi Candida albicans and Aspergillus fumigatus

Abstract

ObjectiveRecent studies into the antifungal activity of NK-cells against the Aspergillus fumigatus have presented differing accounts on their mode of antifungal activity. One of these mechanisms proposed that NK-cells may kill the fungus via the direct effects of exposure to Interferon gamma (IFN-γ).ResultsIn this study we investigated the direct antifungal effects of recombinant human IFN-γ against a range of pathogenic fungi by measuring cellular damage using an XTT-based assay and cell viability through plate counts. It was found that 32 pg/ml of IFN-γ exhibited a significant but small antifungal effect on A. fumigatus (p = 0.02), Aspergillus flavus (p = 0.04) and Saccharomyces cerevisiae (p = 0.03), inhibiting growth by 6, 11 and 17% respectively. No significant inhibitory effects were observed in Candida species (p > 0.05 for all species tested) or Cryptococus neoformans (p = 0.98). Short term exposure (3 h) to a combination of amphotericin B (1 µg/ml) and IFN-γ (32 pg/ml) increased the effectiveness of amphotericin B against A. fumigatus and S. cerevisiae but not Candida albicans. These data suggest that IFN-γ does not possess strong antifungal activity but can enhance the effect of amphotericin B under some testing conditions against Aspergillus species.

Natural Killer Cells in Antifungal Immunity

“…As higher concentrations of IFN-γ, e.g., 50 or 100 pg/ml, did not increase antifungal activity, and IFN-γ serum levels of 18 ± 30 pg/ml can be detected in healthy individuals ( 94 ), the importance of the direct antifungal effect in vivo is questionable. Corroborating the data of another report ( 70 ), no significant antifungal effects of IFN-γ were detected in Candida and C. neoformans ( 93 ). However, it is important to note that a combination of amphotericin B at a concentration of 1 µg/ml and IFN-γ at 32 pg/ml increased the efficacy of amphotericin B against A. fumigatus , which might be important for immunotherapeutic strategies.…”

“…The authors suggested as explanation that “IFN-γ might cooperate with fungal ribotoxins, (…), transforming them into suicide molecules for fungus” ( 65 ). Similarly, it was demonstrated that IFN-γ at a concentration of 32 pg/ml exhibited a small but significant antifungal effect on A. fumigatus, A. flavus , and Saccharomyces cerevisiae , and inhibited the growth by 6, 11, and 17%, respectively ( 93 ). As higher concentrations of IFN-γ, e.g., 50 or 100 pg/ml, did not increase antifungal activity, and IFN-γ serum levels of 18 ± 30 pg/ml can be detected in healthy individuals ( 94 ), the importance of the direct antifungal effect in vivo is questionable.…”

Alteration of macrophage immune phenotype in a murine sepsis model is associated with susceptibility to secondary fungal infection

“…Even so, IFN-γ has recently been used as an adjunctive therapy against fungal infection, 25,26 though treatment with IFN-γ alone was not effective. 27 Although IL-17 has been suggested to play a key role in Candida eradication, its role is restricted to mucosal infections. 28 Furthermore, our recent investigation demonstrated that IFN-γ, but not IL-17, was a significant protective cytokine for host defense against secondary fungal infection in murine sepsis.…”

Assessing Differences between Clinical Isolates of Aspergillus fumigatus from Cases of Proven Invasive Aspergillosis and Colonizing Isolates with Respect to Phenotype (Virulence in Tenebrio molitor Larvae) and Genotype

“…Minimum inhibitory concentrations (MICs) of several antifungal drugs were determined using Yeast Sensititre YO10 plates (ThermoFisher Scientific) as per the manufacturer's instructions [78]. In brief, fungal conidia were added to the included broth as described in the manufacturer's instructions to achieve a density of 1.5-8 × 10 3 cells/mL; 100 µL of broth containing conidia was added to each well of the YO10 Sensititre plate (Ther-moFisher Scientific).…”