Dendritic cell interaction with Candida albicans critically depends on N-linked mannan.
The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, because a detailed characterization at the structural level is lacking. Antigen-presenting dendritic cells (DCs), strategically located at mucosal surfaces and in the skin, may play an important role in anti-Candida protective immunity. However, the contribution of the various Candida-associated molecular patterns and their counter-receptors to DC function remains unknown. Here, we demonstrate that two C-type lectins, DC-SIGN and the macrophage mannose receptor, specifically mediate C. albicans binding and internalization by human DCs. Moreover, by combining a range of C. albicans glycosylation mutants with receptor-specific blocking and cytokine production assays, we determined that N-linked mannan but not O-linked or phosphomannan is the fungal carbohydrate structure specifically recognized by both C-type lectins on human DCs and directly influences the production of the proinflammatory cytokine IL-6. Better insight in the carbohydrate recognition profile of C-type lectins will ultimately provide relevant information for the development of new drugs targeting specific fungal cell wall antigens.
Cambi
Alessandra
A
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Netea
Mihai G
MG
Mora-Montes
Hector M
HM
Gow
Neil A R
NA
Hato
Stanleyson V
SV
Lowman
Douglas W
DW
Kullberg
Bart-Jan
BJ
Torensma
Ruurd
R
Williams
David L
DL
Figdor
Carl G
CG
D002176:Candida albicans / Q000276:immunology*; D015815:Cell Adhesion Molecules / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006031:Glycosylation; D006801:Humans; D037181:Lectins, C-Type / Q000276:immunology; D008351:Mannans / Q000737:chemistry / Q000276:immunology*; D015394:Molecular Structure; D010586:Phagocytes / Q000276:immunology; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000276:immunology; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D015815:Cell Adhesion Molecules; D016207:Cytokines; D037181:Lectins, C-Type; D008351:Mannans; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin