Dectin-2 Is a Direct Receptor for Mannose-Capped Lipoarabinomannan of Mycobacteria

Mycobacteria possess various immunomodulatory molecules on the cell wall. Mannose-capped lipoarabinomannan (Man-LAM), a major lipoglycan of Mycobacterium tuberculosis, has long been known to have both inhibitory and stimulatory effects on host immunity. However, the direct Man-LAM receptor that expl...

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Bibliographic Details
Published in:Immunity (Cambridge, Mass.) Mass.), 2014-09, Vol.41 (3), p.402-413
Main Authors: Yonekawa, Akiko, Saijo, Shinobu, Hoshino, Yoshihiko, Miyake, Yasunobu, Ishikawa, Eri, Suzukawa, Maho, Inoue, Hiromasa, Tanaka, Masato, Yoneyama, Mitsutoshi, Oh-hora, Masatsugu, Akashi, Koichi, Yamasaki, Sho
Format: Article
Language:English
Subjects:
Animals
Antigens, CD - genetics
Cell Adhesion Molecules - genetics
Cytokines
Cytokines - biosynthesis
Dendritic Cells - immunology
Encephalomyelitis, Autoimmune, Experimental - genetics
Encephalomyelitis, Autoimmune, Experimental - immunology
Immune system
Inflammation - immunology
Interferon-gamma - biosynthesis
Interleukin-10 - biosynthesis
Lectins, C-Type - genetics
Lectins, C-Type - immunology
Lipopolysaccharides - chemistry
Lipopolysaccharides - immunology
Mannose - chemistry
Mannose-Binding Lectins - immunology
Medical research
Mice
Mice, Knockout
Mycobacterium bovis - immunology
Mycobacterium Infections - genetics
Mycobacterium Infections - immunology
Mycobacterium tuberculosis
Mycobacterium tuberculosis - immunology
Myeloid Differentiation Factor 88 - genetics
Protein Binding - immunology
Receptors, Cell Surface - genetics
Receptors, Cell Surface - immunology
Receptors, Immunologic - genetics
Studies
T-Lymphocytes - immunology
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Summary:Mycobacteria possess various immunomodulatory molecules on the cell wall. Mannose-capped lipoarabinomannan (Man-LAM), a major lipoglycan of Mycobacterium tuberculosis, has long been known to have both inhibitory and stimulatory effects on host immunity. However, the direct Man-LAM receptor that explains its pleiotropic activities has not been clearly identified. Here, we report that a C-type lectin receptor Dectin-2 (gene symbol Clec4n) is a direct receptor for Man-LAM. Man-LAM activated bone-marrow-derived dendritic cells (BMDCs) to produce pro- and anti-inflammatory cytokines, whereas it was completely abrogated in Clec4n–/– BMDCs. Man-LAM promoted antigen-specific T cell responses through Dectin-2 on DCs. Furthermore, Man-LAM induced experimental autoimmune encephalitis (EAE) as an adjuvant in mice, whereas Clec4n–/– mice were resistant. Upon mycobacterial infection, Clec4n–/– mice showed augmented lung pathology. These results demonstrate that Dectin-2 contributes to host immunity against mycobacterial infection through the recognition of Man-LAM. [Display omitted] •Dectin-2 recognizes mycobacterial Man-LAM•Man-LAM induces both pro- and anti-inflammatory cytokine production through Dectin-2•IL-10 production during mycobacterial infection is abrogated in Clec4n−/− DCs•Man-LAM induces EAE as an adjuvant through Dectin-2-FcRγ signaling axis Mycobacterial lipoarabinomannan is a well-known immunomodulatory component. Yamasaki and colleagues demonstrate that Dectin-2 is a direct receptor for this lipoglycan.
ISSN:1074-7613
1097-4180
DOI:10.1016/j.immuni.2014.08.005