Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus

Autor: Mark H. T. Stappers, Matteo Zanda, Axel A. Brakhage, Mihai G. Netea, Ivy M. Dambuza, António Campos, Delyth M. Reid, Ten Feizi, Carol Wallace, Betty Hebecker, Jean-Paul Latgé, João F. Lacerda, Neil A. R. Gow, Frank L. van de Veerdonk, Maria da Glória Teixeira de Sousa, Patawee Asamaphan, Kyung J. Kwon-Chung, Monica Piras, Martin Jaeger, Cristina Cunha, Vishukumar Aimanianda, Janet A. Willment, Alexandra E. Clark, Raif Yuecel, Chiara Zanato, Isabel Valsecchi, Yan Liu, Agostinho Carvalho, Bernhard Kerscher, Sarah E. Hardison, Anthony Plato, Stefan Bidula, Gordon D. Brown
Přispěvatelé: University of Aberdeen, Aspergillus, Institut Pasteur [Paris], University of Minho [Braga], Imperial College London, Leibniz Institute for Natural Product Research and Infection Biology (Hans Knoell Institute), National Institutes of Health [Bethesda] (NIH), Radboud University Medical Center [Nijmegen], Universidade de Lisboa (ULISBOA), Instituto Português de Oncologia do Porto, Funding was provided by the Wellcome Trust (102705, 097377, 093378, 099197, 108430, 101873), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). K.J.K.-C is supported by the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, V.A. by an ANR-DST COMASPIN grant (ANR-13-ISV3-0004), B.H. by German Science Foundation (www.dfg.de) grant no. HE 7565/1-1, J.-P.L., I.V. and V.A. by the ANR and FRM DEQ2015-331722, A.C. by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and by the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 and SFRH/BPD/96176/2013)., ANR-13-ISV3-0004,COMASPIN,Médiateurs solubles du système immunitaire contre Aspergillus fumigatus(2013), Universidade do Minho, Repositório da Universidade de Lisboa, Institut Pasteur [Paris] (IP), Universidade de Lisboa = University of Lisbon (ULISBOA)
Rok vydání: 2018
Předmět:
0301 basic medicine
[SDV]Life Sciences [q-bio]
lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
MESH: Rats
Sprague-Dawley
Naphthols
[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity
Aspergillus fumigatus
Substrate Specificity
Rats
Sprague-Dawley
Mice
0302 clinical medicine
MESH: Melanins
C-type lectin
COMPETING RISK
Cell Wall
MESH: Animals
Receptor
MYELOID CELLS
Multidisciplinary
biology
BETA-GLUCAN RECEPTOR
Effector
Pattern recognition receptor
Spores
Fungal
3. Good health
Multidisciplinary Sciences
[SDV.IMM]Life Sciences [q-bio]/Immunology
Science & Technology - Other Topics
Female
MESH: Aspergillus fumigatus
MESH: Rats
SURFACE
General Science & Technology
Microbiology
CLEC-1
03 medical and health sciences
Immune system
MESH: Cell Wall
All institutes and research themes of the Radboud University Medical Center
Immunity
MESH: Mice
Inbred C57BL
MESH: Spores
Fungal
Animals
Aspergillosis
Humans
BIOSYNTHESIS
Lectins
C-Type
MESH: Aspergillosis
MESH: Mice
Melanins
MESH: Humans
Science & Technology
FUMIGATUS
MESH: Naphthols
IDENTIFICATION
Macrophages
Lectin
MESH: Macrophages
biology.organism_classification
ENDOTHELIAL-CELLS
GENE
Rats
Mice
Inbred C57BL
030104 developmental biology
biology.protein
MESH: Substrate Specificity
MESH: Female
MESH: Lectins
C-Type
030215 immunology
Zdroj: Nature, 555, 7696, pp. 382-386
Nature
Nature, Nature Publishing Group, 2018, 555 (7696), pp.382-386. ⟨10.1038/nature25974⟩
Nature, 555, 382-386
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Nature, 2018, 555 (7696), pp.382-386. ⟨10.1038/nature25974⟩
ISSN: 2015-3317
0028-0836
1476-4679
1476-4687
Popis: © 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.
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.
Funding was provided by the Wellcome Trust (102705, 097377, 093378, 099197, 108430, 101873), the Medical Research Council Centre for Medical Mycology and the University of Aberdeen (MR/N006364/1). K.J.K.-C is supported by the intramural program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health; V.A. by an ANR-DST COMASPIN grant (ANR-13-ISV3-0004); B.H. by German Science Foundation (www.dfg.de) grant no. HE 7565/1-1; J.-P.L., I.V. and V.A. by the ANR and FRM DEQ2015-331722; A.C. by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER) (NORTE-01-0145-FEDER-000013), and by the Fundação para a Ciência e Tecnologia (FCT) (IF/00735/2014 and SFRH/BPD/96176/2013)
Databáze: OpenAIRE
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