Trudeau Institute, Saranac Lake, NY 12983, USA.
Cell Host Microbe. 2009 Dec 17;6(6):503-12. doi: 10.1016/j.chom.2009.11.003.
Surviving infection represents a balance between the proinflammatory responses needed to eliminate the pathogen, and anti-inflammatory signals limiting damage to the host. IL-10 is a potent immunosuppressive cytokine whose impact is determined by the timing and localization of release. We show that NK cells rapidly express IL-10 during acute infection with diverse rapidly disseminating pathogens. The proinflammatory cytokine IL-12 was necessary and sufficient for NK cell induction of IL-10. NK cells from mice with systemic parasitic infection inhibited dendritic cell release of IL-12 in an IL-10-dependent manner, and NK cell depletion resulted in elevated serum IL-12. These data suggest an innate, negative feedback loop in which IL-12 limits its own production by eliciting IL-10 from NK cells. In contrast to disseminating pathogens, locally restricted infections did not elicit NK cell IL-10. Thus systemic infections uniquely engage NK cells in an IL-10-mediated immunoregulatory circuit that functions to alleviate inflammation.
感染后存活代表着消除病原体所需的促炎反应与限制宿主损伤的抗炎信号之间的平衡。IL-10 是一种强效的免疫抑制细胞因子，其影响取决于释放的时间和位置。我们发现，NK 细胞在多种快速传播的病原体急性感染期间迅速表达 IL-10。促炎细胞因子 IL-12 对于 NK 细胞诱导 IL-10 是必需且充分的。来自全身性寄生虫感染小鼠的 NK 细胞以 IL-10 依赖的方式抑制树突状细胞释放 IL-12，而 NK 细胞耗竭导致血清中 IL-12 升高。这些数据表明存在一种先天的负反馈环，其中 IL-12 通过从 NK 细胞中引发 IL-10 来限制自身的产生。与传播性病原体不同，局部受限感染不会引发 NK 细胞产生 IL-10。因此，全身性感染独特地使 NK 细胞参与 IL-10 介导的免疫调节回路，从而减轻炎症。
