Abstract
C-type lectin receptors (CLRs) constitute a category of innate immune receptors that play an essential role in the antifungal immune response. For over two decades, scientists have uncovered what are the fungal ligands recognized by CLRs and how these receptors initiate the immune response. Such studies have allowed the identification of genetic polymorphisms in genes encoding for CLRs or for proteins involved in the signalisation cascade they trigger. Nevertheless, our understanding of how these receptors functions and the full extent of their function during the antifungal immune response is still at its infancy. In this review, we summarize some of the main findings about CLRs in antifungal immunity and discuss what the future might hold for the field.
Original language | English |
---|---|
Article number | e12951 |
Pages (from-to) | e12951 |
Journal | Parasite immunology |
Volume | 45 |
Issue number | 2 |
DOIs | |
Publication status | Published - Feb 2023 |
Externally published | Yes |
Keywords
- Immunological terms
- PAMP
- PRR
- innate immunity
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In: Parasite immunology, Vol. 45, No. 2, e12951, 02.2023, p. e12951.
Research output: Contribution to journal › Review article › Academic › peer-review
TY - JOUR
T1 - C-type lectin receptors in antifungal immunity
T2 - Current knowledge and future developments
AU - Hatinguais, Remi
AU - Willment, Janet A
AU - Brown, Gordon D
N1 - Funding Information: Medical Research Council, Grant/Award Number: MR/N006364/2; Wellcome Trust, Grant/Award Numbers: 217163, 102705 Funding information Funding Information: This research was funded in whole, or in part, by the Wellcome Trust (Grant number 217163 and 102705). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. We also thank the Medical Research Council Centre for Medical Mycology at the University of Exeter for funding (MR/N006364/2). Funding Information: This research was funded in whole, or in part, by the Wellcome Trust (Grant number 217163 and 102705). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. We also thank the Medical Research Council Centre for Medical Mycology at the University of Exeter for funding (MR/N006364/2). Over the last two decades, CLRs have been identified as key actors of antifungal immunity, initiating innate immune responses and directing the development of adaptive immunity23 (Figure 2). The identification of SNPs in the genes encoding for CLRs has allowed us to better understand susceptibility to fungi and are a powerful tool to predict the risk of fungal infections, which could be lifesaving in the case of immunocompromised patients.12 Dissecting the signalling of these receptors has highlighted the central function of the adaptor molecule CARD9 in antifungal immunity26; it has also, for example, provided us with the immunological mechanisms underlying chronic infections by Fonsecaea spp. and how to treat them.30 In order to better understand the role of CLRs in antifungal immunity, future studies will have to integrate the function of these receptors with the inflammatory and metabolic environment, and to consider the presence of endogenous ligands that could also contribute to modulation of the immune response. Studies on the impact of the composition of the mycobiota, the role played by CLRs in shaping its composition and mediating its physiological effects have already provided us with exciting results, and it is very likely that more will be revealed in the future. Overall, CLRs still constitute an important reservoir of potential future therapeutic strategies, including by modulating or blocking their signalling.43 Other translational approaches include targeting CLRs for the development of vaccines, a missing therapeutic weapon in the management of fungal infections.6,79 Excitingly, a Chimeric antigen receptor (CAR) T-cell therapy using the extracellular domain of Dectin-1 to provide the CAR-T cells with a specificity for β-glucans has shown promising results in treating invasive fungal infections.80 Importantly, CLRs, including those primarily described in antifungal immunity, are also involved in the immune response against other pathogenic agents, including parasites, and the antitumoral responses.6 Therefore, it is likely that a number of discoveries (past or future) would have significant implications for the management of other pathologies. The characterization of individual CLRs and their fungal ligands has aided identification of polymorphisms responsible for susceptibility to fungal infections. These studies have enabled us to better understand the mechanisms by which CLRs promote fungal clearance and polarize T cells, notably through deciphering the intracellular signalling cascade induced by CLR triggering. Future developments in the field, including a better understanding of the interplay between CLRs and the mycobiota, as well as the influence of lifestyle, inflammatory microenvironment, notably with the collaboration of CLRs with other PRRs and cytokine receptors, and the role of endogenous ligand binding during fungal infections will eventually lead to the development of new antifungal therapeutic strategies. This research was funded in whole, or in part, by the Wellcome Trust (Grant number 217163 and 102705). For the purpose of open access, the author has applied a CC BY public copyright licence to any author accepted manuscript version arising from this submission. We also thank the Medical Research Council Centre for Medical Mycology at the University of Exeter for funding (MR/N006364/2). Publisher Copyright: © 2022 The Authors. Parasite Immunology published by John Wiley & Sons Ltd.
PY - 2023/2
Y1 - 2023/2
N2 - C-type lectin receptors (CLRs) constitute a category of innate immune receptors that play an essential role in the antifungal immune response. For over two decades, scientists have uncovered what are the fungal ligands recognized by CLRs and how these receptors initiate the immune response. Such studies have allowed the identification of genetic polymorphisms in genes encoding for CLRs or for proteins involved in the signalisation cascade they trigger. Nevertheless, our understanding of how these receptors functions and the full extent of their function during the antifungal immune response is still at its infancy. In this review, we summarize some of the main findings about CLRs in antifungal immunity and discuss what the future might hold for the field.
AB - C-type lectin receptors (CLRs) constitute a category of innate immune receptors that play an essential role in the antifungal immune response. For over two decades, scientists have uncovered what are the fungal ligands recognized by CLRs and how these receptors initiate the immune response. Such studies have allowed the identification of genetic polymorphisms in genes encoding for CLRs or for proteins involved in the signalisation cascade they trigger. Nevertheless, our understanding of how these receptors functions and the full extent of their function during the antifungal immune response is still at its infancy. In this review, we summarize some of the main findings about CLRs in antifungal immunity and discuss what the future might hold for the field.
KW - Immunological terms
KW - PAMP
KW - PRR
KW - innate immunity
UR - http://www.scopus.com/inward/record.url?scp=85139443176&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/pim.12951
DO - https://doi.org/10.1111/pim.12951
M3 - Review article
C2 - 36114607
SN - 0141-9838
VL - 45
SP - e12951
JO - Parasite immunology
JF - Parasite immunology
IS - 2
M1 - e12951
ER -