PDF(Pubmed)
Abstract：
BACKGROUND: A dysregulated immune system is a major driver of the mortality and long-term morbidity from sepsis. With respect to macrophages, it has been shown that phenotypic changes are critical to effector function in response to acute infections, including intra-abdominal sepsis. Invariant natural killer T cells (iNKT cells) have emerged as potential central regulators of the immune response to a variety of infectious insults. Specifically, various iNKT cell:macrophage interactions have been noted across a spectrum of diseases, including acute events such as sepsis. However, the potential for iNKT cells to affect peritoneal macrophages during an abdominal septic event is as yet unknown.
METHODS: Cecal ligation and puncture (CLP) was performed in both wild type (WT) and invariant natural killer T cell knockout (iNKT-/-) mice. 24 h following CLP or sham operation, peritoneal macrophages were collected for analysis. Analysis of macrophage phenotype and function was undertaken to include analysis of bactericidal activity and cytokine or superoxide production.
RESULTS: Within iNKT-/- mice, a greater degree of intraperitoneal macrophages in response to the sepsis was noted. Compared to WT mice, within iNKT-/- mice, CLP did induce an increase in CD86+ and CD206+, but no difference in CD11b+. Unlike WT mice, intra-abdominal sepsis within iNKT-/- mice induced an increase in Ly6C-int (5.2% versus 14.9%; P < 0.05) and a decrease in Ly6C-high on peritoneal macrophages. Unlike phagocytosis, iNKT cells did not affect macrophage bactericidal activity. Although iNKT cells did not affect interleukin-6 production, iNKT cells did affect IL-10 production and both nitrite and superoxide production from peritoneal macrophages.
CONCLUSIONS: The observations indicate that iNKT cells affect specific phenotypic and functional aspects of peritoneal macrophages during polymicrobial sepsis. Given that pharmacologic agents that affect iNKT cell functioning are currently in clinical trial, these findings may have the potential for translation to critically ill surgical patients with abdominal sepsis.
METHODS: Cecal ligation and puncture (CLP) was performed in both wild type (WT) and invariant natural killer T cell knockout (iNKT-/-) mice. 24 h following CLP or sham operation, peritoneal macrophages were collected for analysis. Analysis of macrophage phenotype and function was undertaken to include analysis of bactericidal activity and cytokine or superoxide production.
RESULTS: Within iNKT-/- mice, a greater degree of intraperitoneal macrophages in response to the sepsis was noted. Compared to WT mice, within iNKT-/- mice, CLP did induce an increase in CD86+ and CD206+, but no difference in CD11b+. Unlike WT mice, intra-abdominal sepsis within iNKT-/- mice induced an increase in Ly6C-int (5.2% versus 14.9%; P < 0.05) and a decrease in Ly6C-high on peritoneal macrophages. Unlike phagocytosis, iNKT cells did not affect macrophage bactericidal activity. Although iNKT cells did not affect interleukin-6 production, iNKT cells did affect IL-10 production and both nitrite and superoxide production from peritoneal macrophages.
CONCLUSIONS: The observations indicate that iNKT cells affect specific phenotypic and functional aspects of peritoneal macrophages during polymicrobial sepsis. Given that pharmacologic agents that affect iNKT cell functioning are currently in clinical trial, these findings may have the potential for translation to critically ill surgical patients with abdominal sepsis.
摘要：
背景：免疫系统失调是脓毒症死亡率和长期发病率的主要驱动因素。关于巨噬细胞，研究表明，表型变化对急性感染的效应子功能至关重要，包括腹内脓毒症.不变的自然杀伤T细胞（iNKT细胞）已成为对各种感染性损伤的免疫反应的潜在中央调节因子。具体来说,各种iNKT细胞：巨噬细胞相互作用已经在一系列疾病中被注意到，包括脓毒症等急性事件。然而,iNKT细胞在腹部脓毒症事件期间影响腹膜巨噬细胞的可能性尚不清楚.
方法：在野生型（WT）和不变的自然杀伤T细胞敲除（iNKT-/-）小鼠中进行盲肠结扎和穿刺（CLP）。CLP或假手术后24小时，收集腹膜巨噬细胞用于分析。进行巨噬细胞表型和功能的分析以包括杀菌活性和细胞因子或超氧化物产生的分析。
结果：在iNKT-/-小鼠中，观察到腹膜内巨噬细胞对脓毒症的反应程度更高.与WT小鼠相比，在iNKT-/-小鼠内，CLP确实诱导了CD86+和CD206+的增加，但CD11b+没有差异。与WT小鼠不同，iNKT-/-小鼠腹内脓毒症诱导了Ly6C-int的增加(5.2%对14.9%;P<0.05)和腹膜巨噬细胞上Ly6C-high的减少。与吞噬作用不同,iNKT细胞不影响巨噬细胞的杀菌活性。虽然iNKT细胞不影响白细胞介素-6的产生，iNKT细胞确实影响IL-10的产生以及来自腹膜巨噬细胞的亚硝酸盐和超氧化物的产生。
结论：观察结果表明，在多微生物败血症期间，iNKT细胞会影响腹膜巨噬细胞的特定表型和功能方面。鉴于影响iNKT细胞功能的药物目前正在临床试验中，这些发现可能有可能转化为腹部脓毒症的危重手术患者.
方法：在野生型（WT）和不变的自然杀伤T细胞敲除（iNKT-/-）小鼠中进行盲肠结扎和穿刺（CLP）。CLP或假手术后24小时，收集腹膜巨噬细胞用于分析。进行巨噬细胞表型和功能的分析以包括杀菌活性和细胞因子或超氧化物产生的分析。
结果：在iNKT-/-小鼠中，观察到腹膜内巨噬细胞对脓毒症的反应程度更高.与WT小鼠相比，在iNKT-/-小鼠内，CLP确实诱导了CD86+和CD206+的增加，但CD11b+没有差异。与WT小鼠不同，iNKT-/-小鼠腹内脓毒症诱导了Ly6C-int的增加(5.2%对14.9%;P<0.05)和腹膜巨噬细胞上Ly6C-high的减少。与吞噬作用不同,iNKT细胞不影响巨噬细胞的杀菌活性。虽然iNKT细胞不影响白细胞介素-6的产生，iNKT细胞确实影响IL-10的产生以及来自腹膜巨噬细胞的亚硝酸盐和超氧化物的产生。
结论：观察结果表明，在多微生物败血症期间，iNKT细胞会影响腹膜巨噬细胞的特定表型和功能方面。鉴于影响iNKT细胞功能的药物目前正在临床试验中，这些发现可能有可能转化为腹部脓毒症的危重手术患者.
