Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus
Open accessAbstract
Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.
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MelLec receptors expressed in endothelial and myeloid cells specifically recognize fungal melanin.
“the recent study showing that MelLec receptors, expressed in endothelial and myeloid cells, specifically recognize fungal melanin [ 83 ]”
From Melanin's Journey from Melanocytes to Keratinocytes: Uncovering the Molecular Mechanisms of Melanin Transfer and Processing (2023) · cites this paper as [83]
The opening summary reports that MelLec recognizes DHN-melanin and is expressed by endothelial cells in mice and myeloid cells in humans. The recognition passage adds that MelLec did not detect melanin made through other pathways, including that of Cryptococcus neoformans. The claim is therefore too broad if “fungal melanin” means fungal melanin generally, and it omits the species distinction in cell expression. (LLM, conf=0.85)
Experimental — accuracy not yet measuredA specific DHN-melanin C-type lectin receptor that triggers immune activation has been found on host immune cells.
“A specific DHN-melanin C-type lectin receptor that triggers immune activation has been found on host immune cells (262), but its role during infection is not yet clear.”
From Aspergillus fumigatus and Aspergillosis in 2019 (2019) · cites this paper as [262]
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References 46 · Cited by 200
Research works printed but not linked: 1
- [40]Stoll MS Feizi T Proceeding of the Beilstein Symposium on Glyco-Bioinformatics 2009 123 140
- Authors
- Stappers, M. H. T., Clark, A. E., Aimanianda, V., Bidula, S., Reid, D. M., Asamaphan, P., Hardison, S. E., Dambuza, I. M., Valsecchi, I., Kerscher, B., Plato, A., Wallace, C. A., Yuecel, R., Hebecker, B., da Glória Teixeira Sousa, M., Cunha, C., Liu, Y., Feizi, T., Brakhage, A. A., Kwon-Chung, K. J., Gow, N. A. R., Zanda, M., Piras, M., Zanato, C., Jaeger, M., Netea, M. G., van de Veerdonk, F. L., Lacerda, J. F., Campos, A., Carvalho, A., Willment, J. A., Latgé, J.-P., & Brown, G. D.
- Affiliations
- University of Aberdeen (GB)
- Institut Pasteur (FR)
- University of Minho (PT)
- Imperial College London (GB)
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie e. V. - Hans-Knöll-Institut (HKI) (DE)
- National Institutes of Health (US)
- Radboud University Medical Center (NL)
- University of Lisbon (PT)
- IPO Porto (PT)
- Corresponding author
- Brown, Gordon D.
- ORCID
- Stappers, Mark H. T.
- Aimanianda, Vishukumar
- Bidula, Stefan
- Asamaphan, Patawee
- Dambuza, Ivy M.
- Kerscher, Bernhard
- Wallace, Carol A.
- Yuecel, Raif
- Cunha, Cristina
- Liu, Yan
- Feizi, Ten
- Brakhage, Axel A.
- Gow, Neil A. R.
- Zanda, Matteo
- Piras, Monica
- Zanato, Chiara
- Jaeger, Martin
- Netea, Mihai G.
- Lacerda, João F.
- Campos, António
- Carvalho, Agostinho
- Willment, Janet A.
- Latgé, Jean-Paul
- Brown, Gordon D.
- Venue
- Nature
- Published
- 2018-02-28
- Volume
- 555
- Issue
- 7696
- Pages
- 382-386
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC5857201
- OpenAlex
- W2789607808
- Cited by
- 200
- References
- 46
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 21 · 2023: 18 · 2022: 24 · 2021: 33 · 2020: 33 · 2019: 27 · 2018: 19
- FWCI
- 21.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Aberdeen University Research Archive (Aberdeen University) (submittedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion, cc-by-sa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Radboud Repository (Radboud University) (submittedVersion)
- Spiral (Imperial College London) (submittedVersion)
- UEA Digital Repository (University of East Anglia) (submittedVersion)
- Funders
- Wellcome Trust (101873/A/13/Z, 097377/Z/11/Z, 097377, 099197, 101873, 108430, 102705, 093378, 102705/Z/13/Z)
- University of Aberdeen (MR/N006364/1)
- Department of Science and Technology, Ministry of Science and Technology, India
- Agence Nationale de la Recherche (ANR-13-ISV3-0004)
- Medical Research Council Centre for Medical Mycology (MR/N006364/1)
- National Institutes of Health
- Medical Research Council (MR/N006364/1, MR/N006364, N006364/1)
- Fundação para a Ciência e a Tecnologia (01-0145, NORTE-01–0145-FEDER-000013, IF/00735/2014, NORTE2020, NORTE-01-0145)
- European Regional Development Fund (01-0145-FEDER-000013, NORTE-01-0145-FEDER-000013, NORTE-2020)
- National Institute of Allergy and Infectious Diseases
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- C-type lectin receptors, Aspergillus fumigatus, antifungal immunity, pattern recognition receptors, fungal melanin, endothelial cells, disseminated aspergillosis, single nucleotide polymorphisms, stem cell transplant recipients, myeloid cells, inflammation
- MeSH terms
- Animals, Aspergillosis, Aspergillus fumigatus, Cell Wall, Female, Humans, Macrophages, Melanins, Mice, Inbred C57BL, Naphthols, Spores, Fungal, Substrate Specificity, Rats, Sprague-Dawley, Lectins, C-Type, Mice, Rats
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