Mechanisms of immune responses by toll-like receptor against Infection and organ failure

虽然外科手术损伤可能导致术后免疫抑制，但其机制尚不清楚。本研究的目的是检测TLR2和TLR4在单核细胞上的表达，以及它们在手术损伤后对每种激动剂的反应。受试者为接受胃肠道手术的患者。抽取患者各时间点的外周血单个核细胞(PBMC)，分析其TLR2、TLR4和诱生型一氧化氮合酶(INOS)的表达。TLR2和TLR4在术后第1天和第3天迅速下降并出现最低值。接下来，我们检测巨噬细胞激活脂肽-2或脂多糖诱导的肿瘤坏死因子-α和白介素6的产生。MALP-2刺激的肿瘤坏死因子-α和IL-6的产生在术后第1天显著下降，术后第1天达到最大值，然后逐渐下降。内毒素刺激的肿瘤坏死因子-α的产生在术后明显受到抑制，术后第3天逐渐升高，达到最大值。术后PBMC诱导型一氧化氮合酶水平明显升高。总之，TLR2和TLR4的表达被手术下调，激动剂诱导的细胞因子的产生被瞬时抑制，并通过激活PBMC而很快增加。本研究可能为手术应激下手术后天然免疫功能的调节提供新的见解。

Although surgical insults may induce postoperative immunosuppression, its mechanism remains unknown. The aim of this study was to examine TLR2 and TLR4 expression on monocytes and their responses to each agonist after surgical insults. The subjects were patients who received gastrointestinal surgery. Peripheral blood mononuclear cells (PBMC) at the indicated times were extracted from the patients and their TLR2, TLR4 and inducible nitric oxide synthase (iNOS) expressions were analyzed. TLR2 and TLR4 were rapidly decreased and showed lowest values on the 1st and 3rd postoperative days, respectively. Next, we measured Macrophage-activating lipopeptide-2 (MALP-2)- or lipopolysaccharide (LPS)- induced TNF- α and IL-6 production. MALP-2-stimulated TNF- α and IL-6 production was significantly decreased after surgery and increased to a maximum value on the 1st postoperative day, then gradually decreased. LPS-stimulated TNF- α production was significantly suppressed after surgery then showed a gradual increase to maximum values on the 3rd postoperative day. iNOS in PBMC was significantly induced after surgery. In conclusion, expression of TLR2 and TLR4 was down-regulated by surgery, and agonist-induced cytokine production was transiently suppressed and soon increased through activation of PBMC. The present study may offer new insights for postoperative modulation of innate immunity under surgical stress.