Human genetic susceptibility to Candida infections

Abstract

Infections with Candida spp. have different manifestations in humans, ranging from mucosal to bloodstream and deep-seated disseminated infections. Immunocompromised patients have increased susceptibility to these types of infections, due to reduced capacity to elicit effective innate or adaptive immunity. In addition, rare and common genetic variants in the human genome have been identified that influence susceptibility to Candida infections. Genetic determinants of primary immunodeficiencies leading to chronic mucocutaneous candidiasis have been reported, and polymorphisms in genes that are known to be involved in anti-Candida host defense are associated with increased susceptibility to systemic infection. These findings have greatly increased our understanding of pathways important for anti-Candida defense in humans, and patterns of prevalence of Candida infections. In addition, these pathways may offer novel therapeutic targets for treatment. This review provides an overview of the current insights in genetic susceptibility to Candida infections and their consequences for the immune response against Candida.

Fig. 1

Schematic overview of proteins involved in anti-Candida host defense of which genetic variants have been identified to increase susceptibility to either mucosal or systemic Candida infection. Only those proteins, and the context of these proteins within antifungal immunity, are depicted of which genetic variants in the encoding genes are associated with an increased susceptibility to infection. These proteins have diverse functions, ranging from recognition of Candida, cytokine signaling and cellular immunity. TLR, Toll-like receptor; MR, mannose receptor.