通常认为新生儿的天然免疫系统和获得性免疫系统尚未发育成熟，由此导致 新生儿不能有效控制和清除病原微生物的感染，从而呈现临床上常见的新生 儿尤其是早产儿感染的高致病率和高死亡率。研究人员发现，相对于成年鼠 ，注射脂多糖(LPS)、合成RNA(polyIC)以及肝炎病毒感染激活天然免疫系统 後，新生鼠产生更强烈的炎症反应，而这种过激的炎症反应正是导致新生鼠 死亡的直接原因。通过进一步研究发现，虽然新生鼠的T细胞具有和成年鼠一 样的抑制炎症反应能力，但由于缺乏足够数量的T细胞，新生鼠在控制炎症反 应的能力方面比成年鼠明显降低。新生鼠在补充了T细胞或者基因敲除炎性因 子的受体(TNFR)後，可以显着降低感染後的炎性反应和死亡率。这一新的发 现进一步证实了研究人员早先提出的“T细胞通过参与天然免疫应答而抑制肝 炎病毒急性感染导致的炎性反应”的理论，并提出了T细胞数目而非T细胞功 能参与调节天然免疫炎症反应的新思路，T细胞数目的不足可能导致新生儿/ 新生鼠感染後呈现高死亡率。该发现将为新生儿，尤其是早产儿急性感染的 诊断与治疗提供新的理论指导。 Hyper innate responses in neonates lead to increased morbidity and mortality after infection 摘要 Neonates suffer high morbidity and mortality in infection, presumably because of the lack of a fully developed adaptive and innate immune system. Evidence of poor innate responses in neonates has been shown by using a model that sensitizes the host to Toll-like receptor (TLR)-mediated inflammation with D-galactosamine (D-GalN). However, we show that neonatal mice demonstrate much stronger inflammatory responses than adult mice in response to LPS stimulation, and such hypersensitivity extends to other TLR agonists including actual viral infection. Our study reveals that the ensuing inflammatory reaction after D-GalN sensitization reflects preferential toxicity of D-GalN to adult liver cells, rather than accurately reflecting the TLR response to LPS. We show further that an uncontrolled proinflammatory innate response due to inadequate T cells makes neonates more vulnerable to TLR agonists or viral infection. Remarkably, through transfer of T cells into neonates or depletion of T cells in adult mice, we show that T cells are sufficient and necessary to control the early inflammatory response to LPS. Therefore, neonates might suffer from the unleashed innate responses caused by an insufficient number of T cells, which leads to increased morbidity and mortality. --

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