Cytokines in Candidiasis and Aspergillosis

Both innate and T helper (Th) immunity play a central role in fungal infections. A bi-directional influence exists between the two compartments of the immune system, mainly occurring through cytokine production. On the one hand, protective Th1 or nonprotective Th2 cells mediate resistance or susceptibility to disseminated and localized fungal infections by secreting cytokines with activating or deactivating signals for effector phagocytic cells. On the other hand, cells of the innate immune system regulate the development of antifungal T helper responses by producing directive cytokines, such as interleukin (IL)-12 and IL-10. In experimental models of Candida albicans and Aspergillus fumigatus infections, the administration or neutralization of selective cytokines and the use of cytokine-deficient mice have revealed the existence of a hierarchical pattern of cytokine mediated regulation of antifungal Th cell development and effector function. A finely regulated balance of directive cytokines, rather than the relative absence of opposing cytokines, appears to be required for optimal development and maintenance of protective Th1 reactivity to fungi. Thus, it is conceivable that some cytokines may have beneficial or deleterious effects on infection, depending on the dose and timing of endogenous production or exogenous administration. A better understanding of the different, sometimes unexpected, roles of cytokines is required for their use in prophylaxis and therapy of fungal infections, either alone or in combination with antifungal agents.