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Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge.

Authors
  • Kerscher, Bernhard1
  • Wilson, Gillian J1
  • Reid, Delyth M1
  • Mori, Daiki2
  • Taylor, Julie A1
  • Besra, Gurdyal S3
  • Yamasaki, Sho2
  • Willment, Janet A1
  • Brown, Gordon D1
  • 1 Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
  • 2 Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Kyushu, Japan. , (Japan)
  • 3 School of Biosciences, University of Birmingham, Birmingham, UK.
Type
Published Article
Journal
European Journal of Immunology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Feb 01, 2016
Volume
46
Issue
2
Pages
381–389
Identifiers
DOI: 10.1002/eji.201545858
PMID: 26558717
Source
Medline
Keywords
License
Unknown

Abstract

The C-type lectin receptor (CTLR), Clec4d (MCL, CLECSF8), is a member of the Dectin-2 cluster of CTLRs, which also includes the related receptors Mincle and Dectin-2. Like Mincle, Clec4d recognizes mycobacterial cord factor, trehalose dimycolate, and we recently demonstrated its key role in anti-mycobacterial immunity in mouse and man. Here, we characterized receptor expression in naïve mice, under inflammatory conditions, and during Mycobacterium bovis BCG infection using newly generated monoclonal antibodies. In naïve mice, Clec4d was predominantly expressed on myeloid cells within the peritoneal cavity, blood, and bone marrow. Unexpectedly, basal expression of Clec4d was very low on leukocytes in the lung. However, receptor expression was significantly upregulated on pulmonary myeloid cells during M. bovis BCG infection. Moreover, Clec4d expression could be strongly induced in vitro and in vivo by various microbial stimuli, including TLR agonists, but not exogenous cytokines. Notably, we show that Clec4d requires association with the signaling adaptor FcRγ and Mincle, but not Dectin-2, for surface expression. In addition, we provide evidence that Clec4d and Mincle, but not Dectin-2, are interdependently coregulated during inflammation and infection. These data show that Clec4d is an inducible myeloid-expressed CTLR in mice, whose expression is tightly linked to that of Mincle.

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