Host receptor-mediated responses to Candida albicans: An update

Candida albicans is a commonly encountered dimorphic fungus that normally resides in the human body. Once the host is immune-compromised or endures long-term antibiotic treatment, C. albicans will transform into an opportunistic pathogen that can cause from superficial mucosal diseases (e.g., oropharyngeal candidiasis) to life-threatening invasive infections (e.g., candidemia). Since the resistance rate of clinical C. albicans is rapidly increasing, there is an urgency to expand the current antifungal armamentarium. It has been shown that a growing body of host receptors can recognize the cell wall components of C. albicans (e.g., β-glucan, chitin and mannan), and trigger potent innate immune responses with enhanced phagocytosis, reactive oxygen species, and inflammatory cytokine production. In this review, we classify the host receptors into two categories: the receptors that directly interact with the epitopes of C. albicans, and those that act as co-receptors to aid in epitope recognition. The former receptors include Dectin-1/2/3, Mincle, MR, DC-SIGN, MBL, CR3, LYSMD3, NKp30 and SPINK7, whereas the latter ones consist of TLR2/4, EphA2/B2, galectin-3, gC1qR, AhR, EGFR and HER2. We not only characterize the antifungal modes of these host receptors during C. albicans infection, but also summarize the features underlying the recognition of C. albicans epitopes by these receptors. The advancements in PRRs can largely expand our scientific understanding of antifungal mechanisms, and lay a solid foundation for the development of new antifungal agents for the clinical treatment of systemic infections caused by C. albicans.