C-type Lectin Receptor: Old Friend and New Player

Abstract

During the last two decades, C-type lectin receptors (CLRs) have been demonstrated to play key roles in initiating the host immune response against fungal infection. It is well established that CLRs, such as Dectin-1, Dectin-2, Dectin-3 and Mincle recognize the cell wall component from the infected microorganisms by using their carbohydrate recognition domain (CRD). Upon stimulation, CLRs induce multiple signal transduction cascades through their own immunereceptor tyrosine-based activation motifs (ITAMs) or interacting with ITAM-containing adaptor proteins such as FcRγ, which then lead to the activation of nuclear factor kappa B (NF-κB) through Syk- and CARD9-dependent pathway. Dissecting CLR signal cascades and their effects on host immune cells is essential to understand the molecular mechanisms in regulating host antifungal immunity. Recently, the activated CLRs including Dectin-1 and Dectin-2 are reported to undergo lysome-mediated degradation by an E3 ubiquitin ligase CBL-b. Moreover, structural analysis will help understand the molecular mechanism of these CLRs and provide clues to rational design for effective anti-fungal drugs. Overall, we summarize the current knowledge on activating and inhibitory CLRs and discuss how to boost host immune system to fight against invasive fungal infection.

The C-type Lectin Receptor-Driven, Th17 Cell-Mediated Severe Pathology in Schistosomiasis: Not All Immune Responses to Helminth Parasites Are Th2 Dominated

“…In agreement with prior reports revealing a role for the Card9/Bcl10/Malt1 complex downstream of Dectin-2 (62), we demonstrated that the loss of Card9 or the inhibition of Malt1 hinder the production of IL-1β and IL-23 by DCs stimulated with live eggs (40). This is consistent with the role of Malt1 in the Dectin-2-mediated activation of the NF-κB subunit c-Rel, which is a key player in the induction of Th17 responses (63).…”

The mycobiota of the human body: a spark can start a prairie fire

“…CLRs dominate fungal perception and immunity, they can activate the Syk-Card9 pathway through immune receptor tyrosine-based activation motifs (ITAMs) or FcRγ(relate to ITAMs), which in turn activates nuclear factor kappa B(NF-kB) signaling and a series of inflammatory reactions. 126 However, there are differences among receptors (Figure 4), dectin-1 (also known as Clec7a) is a CLR that is expressed by many immunological cells. This molecule recognizes β-glucan and then promotes the production of cytokines to induce inflammation, thus controlling Candida infection mainly.…”

Adjuvant activity of Mycobacteria-derived mycolic acids

“…Lines of evidence have shown that immunoreceptor tyrosine-based activation motif (ITAM)-coupled receptors, including C-type lectin receptors (CLRs) and immunoglobulin superfamily receptors play critical roles in activation of innate immunity against various pathogens [12,13,14,15]. Some of the receptor members, such as Dectin-1/2, and Mincle, are known to sense pathogen-derived material with PAMPs and induce activation of innate immunity [16,17,18,19].…”