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.
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.
- C-type lectin receptor
- innate immunity
- Mycobacterium bovis BCG