title: Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation.
abstract: The heterodimeric mycobacterial receptors, macrophage C-type lectin (MCL) and macrophage inducible C-type lectin (Mincle), are upregulated at the cell surface following microbial challenge, but the mechanisms underlying this response are unclear. Here we report that microbial stimulation triggers Mincle expression through the myeloid differentiation primary response gene 88 (MyD88) pathway; a process that does not require MCL. Conversely, we show that MCL is constitutively expressed but retained intracellularly until Mincle is induced, whereupon the receptors form heterodimers which are translocated to the cell surface. Thus this "two-step" model for induction of these key receptors provides new insights into the underlying mechanisms of anti-mycobacterial immunity.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kerscher
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Ivy M
authors.initials: IM
authors.lastname: Dambuza
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Christofi
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
authors.forename: Delyth M
authors.initials: DM
authors.lastname: Reid
authors.affiliation: Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Yamasaki
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: janet.willment@abdn.ac.uk.
authors.forename: Janet A
authors.initials: JA
authors.lastname: Willment
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK. Electronic address: gordon.brown@abdn.ac.uk.
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D009161:Mycobacterium / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*
chemical_list: C584161:Clec4d protein, mouse; C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic
keywords: C-type lectin receptor; Clec4d; Clec4e; Dectin-3; MyD88; TLR signalling