Calvin, Phoebe, and Joan Snyder Institute for Infection, Immunity, and Inflammation, University of Calgary, Calgary, Alberta, Canada.
Science. 2011 Oct 7;334(6052):101-5. doi: 10.1126/science.1210301. Epub 2011 Sep 15.
Systemic immunosuppression has been associated with stroke for many years, but the underlying mechanisms are poorly understood. In this study, we demonstrated that stroke induced profound behavioral changes in hepatic invariant NKT (iNKT) cells in mice. Unexpectedly, these effects were mediated by a noradrenergic neurotransmitter rather than a CD1d ligand or other well-characterized danger signals. Blockade of this innervation was protective in wild-type mice after stroke but had no effect in mice deficient in iNKT cells. Selective immunomodulation of iNKT cells with a specific activator (α-galactosylceramide) promoted proinflammatory cytokine production and prevented infections after stroke. Our results therefore identify a molecular mechanism that leads to immunosuppression after stroke and suggest an attractive potential therapeutic alternative to antibiotics, namely, immunomodulation of iNKT cells to prevent stroke-associated infections.
多年来，系统性免疫抑制与中风有关，但潜在机制尚不清楚。在这项研究中，我们证明中风诱导了小鼠肝脏不变自然杀伤 T(iNKT)细胞的深刻行为改变。出乎意料的是，这些影响是由去甲肾上腺素能神经递质介导的，而不是由 CD1d 配体或其他特征明确的危险信号介导的。这种神经支配的阻断在中风后的野生型小鼠中具有保护作用，但在缺乏 iNKT 细胞的小鼠中没有效果。用特异性激活剂（α-半乳糖神经酰胺）选择性地免疫调节 iNKT 细胞可促进促炎细胞因子的产生，并可预防中风后的感染。因此，我们的结果确定了导致中风后免疫抑制的分子机制，并提出了一种有吸引力的潜在治疗替代抗生素的方法，即免疫调节 iNKT 细胞以预防中风相关感染。
