Inteferon gamma and granulocyte–macrophage colony-stimulating factor augment the antifungal activity of human polymorphonuclear leukocytes againstScedosporiumspp.: comparison withAspergillusspp.

Abstract

While Aspergillus spp. have been the most frequent filamentous fungi causing infections in immunocompromised patients, Scedosporium spp. are emerging as life-threatening pathogens. We studied the effects of interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) alone or combined on the antifungal activities of human polymorphonuclear leukocytes (PMN) against Scedosporium apiospermum and Scedosporium prolificans. We paralleled these activities to those against Aspergillus fumigatus and Aspergillus flavus. Incubation of PMN with IFN-gamma and GM-CSF for 22 h enhanced PMN-induced hyphal damage of both Aspergillus spp. and S. prolificans (p < 0.05) but not of S. apiospermum. However, hyphae of S. apiospermum were damaged significantly more after incubation with PMN that had been treated with IFN-gamma and GM-CSF for 2 h. In addition, incubation of PMN with GM-CSF for 2 h enhanced PMN oxidative burst measured as superoxide anion (O2-) production in response to nonopsonized hyphae of A. flavus and Scedosporium spp. (p < 0.05). In contrast, after 2 h, IFN-gamma and GM-CSF alone did not enhance PMN O2- in response to opsonized hyphae of A. flavus and Scedosporium spp.; however, the combination of IFN-gamma and GM-CSF showed significant enhancement against these species. Thus, IFN-gamma and GM-CSF, particularly in combination, demonstrate a species- and time-dependent augmentation of PMN responses to Scedosporium spp.

Immunomodulatory Effects of Voriconazole on Monocytes Challenged withAspergillus fumigatus: Differential Role of Toll-Like Receptors

“…After the initial proinflammatory response to A. fumigatus associated with TLRs, phagocytes use both oxidative and nonoxidative mechanisms in concert to damage the hyphae of A. fumigatus (9,29). While a number of cytokines upregulate these antifungal phagocytic activities (12,14,16), antifungal agents may assist in further damaging hyphae. Sau et al found that amphotericin B induces signal transduction and inflammatory cytokine release from cells expressing TLR2, and the adapter protein MyD88 responds to amphotericin B with NF-B-dependent reporter activity and cytokine release (28a).…”

Infections Caused byScedosporiumspp

“…Among the clinically available cytokines studied that enhance PMN antifungal activity against Scedosporium spp. are gamma interferon (IFN-␥) and GM-CSF (153). Treatment of PMNs with the combination of IFN-␥ and GM-CSF had broader effects on Scedosporium spp., enhancing PMN functions, while cytokines alone had no effect.…”

“…Thus, in that study it was demonstrated that IFN-␥ and GM-CSF exhibit a significant time-and species-dependent ability to enhance PMN activity against Scedosporium spp. (153).…”

Cross-protective TH1 immunity against Aspergillus fumigatus and Candida albicans

“…[30][31][32] Culture supernatant of activated p41-specific T-cell clones contained high concentrations of both cytokines (supplemental Figure 2) and in addition showed a tendency to improve killing of A fumigatus conidia by monocytes, although differences in conidial uptake by the phagocytes cannot be excluded (supplemental Figure 3). …”