Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation.
Signalling through MyD88 drives surface expression of the mycobacterial receptors MCL (Clecsf8, Clec4d) and Mincle (Clec4e) following microbial stimulation.
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DOI：
10.1016/j.micinf.2016.03.007
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发表时间：
2016-07
影响因子：
5.8
通讯作者：
Brown GD
中科院分区：
文献类型：
--
作者：
Kerscher B;Dambuza IM;Christofi M;Reid DM;Yamasaki S;Willment JA;Brown GD
异源二聚体分枝杆菌受体巨噬细胞C型凝集素(MCL)和巨噬细胞诱导的C型凝集素(Mincle)在微生物攻击后在细胞表面表达上调，但其机制尚不清楚。在这里，我们报告了微生物刺激通过髓系分化初级反应基因88(MyD88)途径触发Mincle表达；这一过程不需要MCL。相反，我们发现MCL是结构性表达的，但在Mincle被诱导之前一直保持在细胞内，于是受体形成异源二聚体，并转移到细胞表面。因此，这种诱导这些关键受体的“两步”模型为研究抗分枝杆菌免疫的潜在机制提供了新的见解。
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.