Candida Pathogenicity and Interplay with the Immune System

Candida species are opportunistic fungal pathogens that are part of the normal skin and mucosal microflora. Overgrowth of Candida can cause infections such as thrush or life-threatening invasive candidiasis in immunocompromised patients. Though Candida albicans is highly prevalent, several non-albicans species are also isolated from nosocomial infections. Candida sp. are over presented in the gut of people with Crohn’s disease and certain types of neurological disorders, with hyphal form and biofilms being the most virulent states. In addition, Candida uses several secreted and cell surface molecules such as pH related antigen 1, High affinity glucose transporter, Phosphoglycerate mutase 1 and lipases to establish pathogenicity. A strong innate immune response is elicited against Candida via dendritic cells, neutrophils and macrophages. All three complement pathways are also activated. Production of proinflammatory cytokines IL-10 and IL-12 signal differentiation of CD4+ cells into Th1 and Th2 cells, whereas IL-6, IL-17 and IL-23 induce Th17 cells. Importance of T-lymphocytes is reflected in depleted T-cell count patients being more prone to Candidiasis. Anti- Candida antibodies also play a role against candidiasis using various mechanisms such as targeting virulent enzymes and exhibiting direct candidacidal activity. However, the significance of antibody response during infection remains controversial. Furthermore, some of the Candida strains have evolved molecular strategies to evade the sophisticated host attack by proteolysis of components of immune system and interfering with immune signalling pathways. Emergence of several non-albicans species that are resistant to current antifungal agents makes treatment more difficult. Therefore, deeper insight into interactions between Candida and the host immune system is required for discovery of novel therapeutic options.