Dectin-1 Signaling Update: New Perspectives for Trained Immunity

Abstract

The C-type lectin receptor Dectin-1 was originally described as the β-glucan receptor expressed in myeloid cells, with crucial functions in antifungal responses. However, over time, different ligands both of microbial-derived and endogenous origin have been shown to be recognized by Dectin-1. The outcomes of this recognition are diverse, including pro-inflammatory responses such as cytokine production, reactive oxygen species generation and phagocytosis. Nonetheless, tolerant responses have been also attributed to Dectin-1, depending on the specific ligand engaged. Dectin-1 recognition of their ligands triggers a plethora of downstream signaling pathways, with complex interrelationships. These signaling routes can be modulated by diverse factors such as phosphatases or tetraspanins, resulting either in pro-inflammatory or regulatory responses. Since its first depiction, Dectin-1 has recently gained a renewed attention due to its role in the induction of trained immunity. This process of long-term memory of innate immune cells can be triggered by β-glucans, and Dectin-1 is crucial for its initiation. The main signaling pathways involved in this process have been described, although the understanding of the above-mentioned complexity in the β-glucan-induced trained immunity is still scarce. In here, we have reviewed and updated all these factors related to the biology of Dectin-1, highlighting the gaps that deserve further research. We believe on the relevance to fully understand how this receptor works, and therefore, how we could harness it in different pathological conditions as diverse as fungal infections, autoimmunity, or cancer.

RIG-I activation primes and trains innate antiviral immune memory

“…While STAT1 in RIG-I signaling acts immediately downstream of paracrine or autocrine IFNAR activation, resulting in a feedforward loop(Schlee & Hartmann, 2016; Rehwinkel & Gack, 2020), the role of STAT1 in β -Glucan training is less clear and has been attributed to IFNγ-signaling from T- and NK-cells(Ifrim et al , 2015). However, Dectin-1 signaling is also known to induce type-I IFN through IRF5(del Fresno et al , 2013; Mata-Martínez et al , 2022) which may contribute to its training effects. Furthermore, a very recent study has also shown that type I IFN-signaling is essential for LPS mediated TI in alveolar macrophages(Zahalka et al , 2022).…”

Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases

“…Candida species are the most common fungal pathogens evoking skin and system infection. Dectin-1 is a significant sensor for β-glucan from Candida [ 112 ]. Dectin-1 and β-glucan can trigger the intracellular transduction pathways of CARD.…”

Long-Term Vaccine Delivery and Immunological Responses Using Biodegradable Polymer-Based Carriers

“…Dextran can be easily captured by macrophages and dendritic cells via scavenger receptors and various lectin-type receptors (Figure ). The C-type lectin receptor-like Dectin1 is present on a wide number of immune cells such as neutrophils monocytes, macrophages, and dendritic cells and can synergize with TLR2 and TLR4, inducing the release of the cytokine in human primary monocytes and macrophage cultures . β-Glucans represent the ligand for dectin, and β-glucan microparticles of different sizes can modulate in different manners the immune responses: larger β-glucans up to 200 mm can stimulate DCs and induce the significantly higher release of IL-1β, IL-6, and IL-23 as compared to those stimulated with the smaller β-glucans of 1–5 mm .…”

“…The C-type lectin receptor-like Dectin1 is present on a wide number of immune cells such as neutrophils monocytes, macrophages, and dendritic cells and can synergize with TLR2 and TLR4, inducing the release of the cytokine in human primary monocytes and macrophage cultures. 111 β-Glucans represent the ligand for dectin, and β-glucan microparticles of different sizes can modulate in different manners the immune responses: larger β-glucans up to 200 mm can stimulate DCs and induce the significantly higher release of IL-1β, IL-6, and IL-23 as compared to those stimulated with the smaller β-glucans of 1−5 mm. 112 Similarly, mannosilated chitosan nanoparticles can bind mannose receptor on the macrophage surface, to enhance their uptake by macrophages and their subsequent entrapment in endosomal/lysosomal compartments where they can be degraded, releasing their cargo.…”