Role of Toll-like receptors in systemic Candida albicans infections

Toll-like receptors (TLRs) constitute a family of pattern-recognition receptors (PRRs) that recognize molecular signatures of microbial pathogens and function as sensors for infection that induce the activation of the innate immune responses as well as the subsequent development of adaptive immune responses. It is well established that TLRs, mainly TLR2 and TLR4, are involved in the host interaction with Candida albicans and play a significant role in the development of host immune responses during candidiasis. Recognition of C. albicans by TLRs on the phagocytic cells activates intracellular signaling pathways that trigger production of proinflammatory cytokines that are critical for innate host defence and orchestrate the adaptive response. T helper (Th) cell reactivity plays a central role in regulating immune responses to C. albicans: Th1-response provides control of fungal infectivity, although this proinflammatory (Th1) host response needs to be counterbalanced through Th2 and regulatory T (Treg) cells to ensure an optimal, protective Th1 response. Recently, a new subset of Th cells, Th17, has been shown to play a role in antifungal immunity, and TLRs may also contribute to the polarization towards a proinflammatory Th17 response. Interaction of C. albicans with TLRs is a complex process as (i) TLR2 may function as an homodimer or as TLR2/TLR1 or TLR2/TLR6 heterodimers and may collaborate with other non-TLR PRRs in recognizing fungal ligands or in triggering intracellular signalling pathways, and in addition (ii) expression of fungal ligands is different at the surface of fungal cells, depending of the morphotype (yeast cells or hyphae), a phenomenon that influences the type of the induced host immune response.