title: Mycobacterial receptor, Clec4d (CLECSF8, MCL), is coregulated with Mincle and upregulated on mouse myeloid cells following microbial challenge.
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.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kerscher
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Gillian J
authors.initials: GJ
authors.lastname: Wilson
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Delyth M
authors.initials: DM
authors.lastname: Reid
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Kyushu, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Mori
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Taylor
authors.affiliation: School of Biosciences, University of Birmingham, Birmingham, UK.
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Kyushu, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Willment
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003311:Cord Factors / Q000378:metabolism*; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology* / Q000382:microbiology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology* / Q000378:metabolism; D022423:Myeloid Cells / Q000276:immunology* / Q000382:microbiology; D010529:Peritoneal Cavity / Q000382:microbiology / Q000473:pathology; D017452:Receptors, IgG / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014376:Tuberculosis / Q000276:immunology* / Q000662:veterinary
chemical_list: C584161:Clec4d protein, mouse; C113583:Clecsf8 protein, mouse; D003311:Cord Factors; D037181:Lectins, C-Type; D008565:Membrane Proteins; D017452:Receptors, IgG; D011971:Receptors, Immunologic; C445340:dectin-2, mouse
keywords: C-type lectin receptor; CLEC4E; CLEC4N; CLECSF8; Innate immunity; MCL; Mycobacterium bovis BCG