Dectin-2 is a direct receptor for mannose-capped lipoarabinomannan of mycobacteria

Immunity. 2014 Sep 18;41(3):402-413. doi: 10.1016/j.immuni.2014.08.005. Epub 2014 Aug 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Cell Adhesion Molecules / genetics
  • Cytokines / biosynthesis
  • Dendritic Cells / immunology
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • 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
  • Mice
  • Mice, Knockout
  • Mycobacterium Infections / genetics
  • Mycobacterium Infections / immunology*
  • Mycobacterium bovis / immunology
  • Mycobacterium tuberculosis / immunology
  • Myeloid Differentiation Factor 88 / genetics
  • Protein Binding / immunology
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Immunologic / genetics
  • T-Lymphocytes / immunology

Substances

  • Antigens, CD
  • Cell Adhesion Molecules
  • Clec4d protein, mouse
  • Cytokines
  • DC-specific ICAM-3 grabbing nonintegrin
  • IL10 protein, mouse
  • Lectins, C-Type
  • Lipopolysaccharides
  • Mannose-Binding Lectins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • SIGNR3 protein, mouse
  • dectin-2, mouse
  • lipoarabinomannan
  • mannose receptor
  • Interleukin-10
  • Interferon-gamma
  • Mannose