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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Myeloid Cells
Mycobacterium bovis
Cord Factors
C-Type Lectins
Infection
Lung
Peritoneal Cavity
Immunity
Leukocytes
Bone Marrow
Monoclonal Antibodies
Cytokines
Inflammation
mouse dectin-2

Keywords

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

Cite this

The mycobacterial receptor, Clec4d (CLECSF8, MCL) is co-regulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. / Kerscher, Bernhard; Wilson, Gillian J.; Reid, Delyth M.; Mori, Daiki; Taylor, Julie A.; Besra, Gurdyal S.; Yamasaki, Sho; Willment, Janet A.; Brown, Gordon D.

In: European Journal of Immunology, Vol. 46, No. 2, 02.2016, p. 381-389.

Research output: Contribution to journalArticle

Kerscher, B, Wilson, GJ, Reid, DM, Mori, D, Taylor, JA, Besra, GS, Yamasaki, S, Willment, JA & Brown, GD 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, vol. 46, no. 2, pp. 381-389. https://doi.org/10.1002/eji.201545858
Kerscher, Bernhard ; Wilson, Gillian J. ; Reid, Delyth M. ; Mori, Daiki ; Taylor, Julie A. ; Besra, Gurdyal S. ; Yamasaki, Sho ; Willment, Janet A. ; Brown, Gordon D. / The mycobacterial receptor, Clec4d (CLECSF8, MCL) is co-regulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. In: European Journal of Immunology. 2016 ; Vol. 46, No. 2. pp. 381-389.
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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 na{\"i}ve mice, under inflammatory conditions, and during Mycobacterium bovis BCG infection using newly generated monoclonal antibodies. In na{\"i}ve 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.",
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note = "Acknowledgements We would like to thank Dr Pierre Redelinghuys, Dr Sabelo Hadebe and the IFCC FACS core facility for reagents and assistance, and the staff of our animal facility for the care of our animals. We would like to thank the Nuffield Foundation for supporting two high school pupils, Mr Christopher Yule and Mr David Gordon, and a summer student from St Andrew’s University, Ms Harriet Bertram, who were involved with the generation of monoclonal antibodies. This work was supported by grants from the MRC and Wellcome Trust to GDB and a University of Aberdeen studentship to BK.",
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T1 - The mycobacterial receptor, Clec4d (CLECSF8, MCL) is co-regulated with Mincle and upregulated on mouse myeloid cells following microbial challenge

AU - Kerscher, Bernhard

AU - Wilson, Gillian J.

AU - Reid, Delyth M.

AU - Mori, Daiki

AU - Taylor, Julie A.

AU - Besra, Gurdyal S.

AU - Yamasaki, Sho

AU - Willment, Janet A.

AU - Brown, Gordon D.

N1 - Acknowledgements We would like to thank Dr Pierre Redelinghuys, Dr Sabelo Hadebe and the IFCC FACS core facility for reagents and assistance, and the staff of our animal facility for the care of our animals. We would like to thank the Nuffield Foundation for supporting two high school pupils, Mr Christopher Yule and Mr David Gordon, and a summer student from St Andrew’s University, Ms Harriet Bertram, who were involved with the generation of monoclonal antibodies. This work was supported by grants from the MRC and Wellcome Trust to GDB and a University of Aberdeen studentship to BK.

PY - 2016/2

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N2 - 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.

AB - 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.

KW - C-type lectin receptor

KW - innate immunity

KW - CLECSF8

KW - MCL

KW - CLEC4E

KW - CLEC4N

KW - Mycobacterium bovis BCG

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DO - 10.1002/eji.201545858

M3 - Article

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VL - 46

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JO - European Journal of Immunology

JF - European Journal of Immunology

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