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

Nature
Mark H T StappersGordon D Brown

Abstract

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 expresse...Continue Reading

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Datasets Mentioned

BETA
GM-CSF

Methods Mentioned

BETA
flow cytometry
ELISA
PCR
FACS
chemical treatments
fluorescence microscopy
flow
bronchoalveolar lavage
genotyping
glycosylation

Software Mentioned

GraphPad Prism
MelLec
cmprsk for
R

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