Immunomodulatory Properties of Antifungal Agents on Immune Functions of the Host

The first line and the most effective form of antifungal host defense are comprised by phagocytes, particularly neutrophils and monocytes/macrophages that play a central role in local containment of infection and prevent systemic dissemination. These immune cells are also exposed to antifungal drugs while patients undergo systemic antifungal therapy. In the phagocyte-fungus-antifungal drug interplay, drugs including amphotericin B formulations, azoles, and echinocandins may directly interact with phagocytes through specific pattern recognition receptors, leading to altered antifungal activities. Drugs, through modulation of fungal virulence, may initiate different immune response pathways in the phagocytes, leading to upregulation of gene expression for a pro-inflammatory response or to antifungal synergism versus antagonism. Additionally, indirect modulation of mononuclear innate immune cell behavior by pretreatment with cytokines and exposure to antifungal agents has shown a promising outcome for combined drug-cytokine therapy in certain difficult to treat life-threatening invasive fungal diseases. In this chapter, the immunomodulatory role of antifungal agents on phagocytic immune cells in response to fungal stimulation is presented. The underlying mechanisms and the potential clinical relevance of such antifungal effects are also discussed.