Soluble mediators in anti-fungal immunity

•Soluble mediators exert antifungal properties directly or indirectly.•They are unaffected or partially affected by immunosuppression, unlike cellular immunity.•Most soluble mediators are pattern recognition receptors, linking fungi to phagocytes.•Soluble mediator based antifungal immunotherapies are gaining attention.•Immune-based antifungal strategies should exploit properties of soluble mediators. Although soluble mediators of our innate immune system have a substantial impact on invading microbes, their role against fungal pathogens has been underexplored. Constituting the humoral immunity, soluble mediators comprise the complement system, collectins, acute-phase proteins, antibodies and antimicrobial peptides. These components can prevent fungal infection either by directly interacting with invading microbes, leading to their aggregation (microbistatic), destruction (microbicidal) or linking them to cellular immunity. The composition of soluble-mediator varies with human body-fluids, resulting in different antifungal mechanisms. Moreover, cellular immune system deploys both oxidative and non-oxidative mechanisms to destroy extracellular or internalized fungal pathogens; however, cellular immune activation is mainly influenced as well as regulated by soluble mediators. This review outlines the antifungal mechanism employed, directly or indirectly, by soluble mediators, and in response, the evading strategies of the fungal pathogens.