Candida albicans at Host Barrier Sites: Pattern Recognition Receptors and Beyond

Abstract

Over the last decades, fungal infections have emerged as a growing threat to human health. Although the human body is at potential risk, various body sites host several commensal fungal species, including Candida albicans. In healthy individuals, C. albicans colonizes different mucosal surfaces without causing harm, while under diverse circumstances the fungus can proliferate and cause disease. In this context, the understanding of host–C. albicans interactions in health and during infection may lead to novel therapeutic approaches. Importantly, host cells express pattern recognition receptors (PRRs), which sense conserved fungal structures and orchestrate innate immune responses. Herein, important findings on the topic of the recognition of C. albicans at host barrier sites are discussed. This review briefly summarizes the importance and functions of myeloid PRRs, reviews the fungal recognition and biology of stromal cells, and highlights important C. albicans virulence attributes during site-specific proliferation and invasion.

Mechanisms of Pathogenic Candida Species to Evade the Host Complement Attack

“…Such an event has also been associated with a milder host response, compared to the response followed by a normal opsonization process, enabling intracellular survival and avoiding the hostile extracellular niche (Würzner and Zipfel, 2004). To date, it is still unclear whether C. albicans uses a Trojan horse-like mechanism for host cell invasion, let alone if such an event would take place with the help of host complement receptors (Swidergall, 2019). Molecular mimicry of host complement proteins is another potential route of host response evasion.…”

New Insights in Candida albicans Innate Immunity at the Mucosa: Toxins, Epithelium, Metabolism, and Beyond

“…Notably, recent studies have shown that intraspecific differences not associated with fungal morphology between C. albicans isolates lead to diverse recognition/immune responses by the oral epithelium (Kirchner et al, 2019), although virtually all strains induce conserved IL-17-mediated responses (Schönherr et al, 2017). Thus, this highlights the importance of other fungal factors that contribute to the balance between commensalism and pathogenesis in the oral cavity (Swidergall, 2019).…”

“…Mucosal immunity to Candida has extensively been reviewed recently, including its recognition by and interactions with epithelial cells (Naglik et al, 2017;Richardson et al, 2018;Nikou et al, 2019;Swidergall, 2019), and the role of innate immune cells FIGURE 1 | Mucosal innate immunity to Candida albicans. Recognition of C. albicans by epithelial cells is mainly mediated by the β-glucan receptor Eph2A.…”

“…Once C. albicans has adhered, epithelial cells detect pathogen-associated molecular patterns (PAMPs; e.g., β-glucans or mannans) and other fungal markers resulting in activation of host cell responses. Although host sensing of C. albicans has been studied to a greater or lesser extent for both epithelial and immune cells, it is still not completely understood (Swidergall, 2019). Several types of pattern recognition receptors (PRRs) mediate Candida recognition by innate immune cells, including Toll-like or C-type lectin receptors, but their relevance at the mucosa may well be different to the systemic environment (Swidergall, 2019).…”

“…Although host sensing of C. albicans has been studied to a greater or lesser extent for both epithelial and immune cells, it is still not completely understood (Swidergall, 2019). Several types of pattern recognition receptors (PRRs) mediate Candida recognition by innate immune cells, including Toll-like or C-type lectin receptors, but their relevance at the mucosa may well be different to the systemic environment (Swidergall, 2019). In fact, while dectin-1 is critical during systemic infections (Taylor et al, 2007), its role during oropharyngeal candidiasis is minor (Verma et al, 2017b) and its expression can even be downregulated in oral epithelial cells when challenged with the fungus (Moyes et al, 2014).…”