Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge. Issue 2 (8th December 2015)

• Record Type: Journal Article
• Authors: Kerscher, Bernhard; Wilson, Gillian J.; Reid, Delyth M.; Mori, Daiki; Taylor, Julie A.; Besra, Gurdyal S.; Yamasaki, Sho; Willment, Janet A.; Brown, Gordon D.
• Is Part Of: European journal of immunology. Volume 46:Issue 2(2016)
• Page Start: 381
• Page End: 389
• Publication Date: 2015-12-08
• Subjects: C‐type lectin receptor -- CLECSF8 -- CLEC4E -- CLEC4N -- Innate immunity -- MCL -- Mycobacterium bovis BCG; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201545858
• Languages: English
• ISSNs: 0014-2980

Abstract

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.