The mycobacterial receptor, Clec4d (CLECSF8, MCL) is co-regulated with Mincle and upregulated on mouse myeloid cells following microbial challenge

Bernhard Kerscher, Gillian J. Wilson, Delyth M. Reid, Daiki Mori, Julie A. Taylor, Gurdyal S. Besra, Sho Yamasaki, Janet A. Willment, Gordon D. Brown

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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 recognises mycobacterial cord factor, trehalose dimycolate, and we recently demonstrated its key role in anti-mycobacterial immunity in mouse and man. Here, we characterised 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 Mycobacterium 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 signalling 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 co-regulated 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.

Original languageEnglish
Pages (from-to)381-389
Number of pages9
JournalEuropean Journal of Immunology
Volume46
Issue number2
Early online date8 Dec 2015
DOIs
Publication statusPublished - Feb 2016

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Keywords

  • C-type lectin receptor
  • innate immunity
  • CLECSF8
  • MCL
  • CLEC4E
  • CLEC4N
  • Mycobacterium bovis BCG

Cite this

Kerscher, B., Wilson, G. J., Reid, D. M., Mori, D., Taylor, J. A., Besra, G. S., Yamasaki, S., Willment, J. A., & Brown, G. D. (2016). The mycobacterial receptor, Clec4d (CLECSF8, MCL) is co-regulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. European Journal of Immunology, 46(2), 381-389. https://doi.org/10.1002/eji.201545858