Kerscher Bernhard, Dambuza Ivy M, Christofi Maria, Reid Delyth M, Yamasaki Sho, Willment Janet A, Brown Gordon D
Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, UK.
Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Japan.
Microbes Infect. 2016 Jul-Aug;18(7-8):505-9. doi: 10.1016/j.micinf.2016.03.007. Epub 2016 Mar 19.
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.
异二聚体分枝杆菌受体，即巨噬细胞C型凝集素（MCL）和巨噬细胞诱导性C型凝集素（Mincle），在受到微生物攻击后在细胞表面上调，但其反应的潜在机制尚不清楚。在此，我们报告微生物刺激通过髓样分化初级反应基因88（MyD88）途径触发Mincle表达；这一过程不需要MCL。相反，我们表明MCL是组成性表达的，但在细胞内保留，直到Mincle被诱导，此时这些受体形成异二聚体并转运到细胞表面。因此，这种诱导这些关键受体的“两步”模型为抗分枝杆菌免疫的潜在机制提供了新的见解。
