[微免] 病毒性肝炎研究新進展

看板Medicine (醫學生物)作者pathoman (青黏材菌)時間16年前 (2008/05/29 13:28)推噓0(0推 0噓 0→)

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通常認為新生兒的天然免疫系統和獲得性免疫系統尚未發育成熟，由此導致新生兒不能有效控制和清除病原微生物的感染，從而呈現臨床上常見的新生兒尤其是早產兒感染的高致病率和高死亡率。研究人員發現，相對于成年鼠，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統後，新生鼠產生更強烈的炎症反應，而這種過激的炎症反應正是導致新生鼠死亡的直接原因。通過進一步研究發現，雖然新生鼠的T細胞具有和成年鼠一樣的抑制炎症反應能力，但由于缺乏足夠數量的T細胞，新生鼠在控制炎症反應的能力方面比成年鼠明顯降低。新生鼠在補充了T細胞或者基因敲除炎性因子的受體(TNFR)後，可以顯著降低感染後的炎性反應和死亡率。這一新的發現進一步證實了研究人員早先提出的“T細胞通過參與天然免疫應答而抑制肝炎病毒急性感染導致的炎性反應”的理論，並提出了T細胞數目而非T細胞功能參與調節天然免疫炎症反應的新思路，T細胞數目的不足可能導致新生兒/ 新生鼠感染後呈現高死亡率。該發現將為新生兒，尤其是早產兒急性感染的診斷與治療提供新的理論指導。 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. -- ※ 發信站: 批踢踢實業坊(ptt.cc) ◆ From: 133.11.70.111 ※ 編輯: pathoman 來自: 133.11.198.91 (05/29 14:30)