Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses
Bacterial reprogramming of PBMCs impairs monocyte phagocytosis and modulates adaptive T cell responses
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DOI：
10.1189/jlb.0911474
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发表时间：
2012-06-01
影响因子：
5.5
通讯作者：
Orlikowsky, Thorsten W.
中科院分区：
文献类型：
--
作者：
Andre, Maya C.;Gille, Christian;Orlikowsky, Thorsten W.
脓毒性疾病的特征在于最初的全身性促炎阶段，随后是一段时间的抗炎。在后者的背景下，单核细胞已被描述为显示改变的功能，包括减少的TNF分泌和T细胞刺激能力，以响应回忆抗原。这种低反应性被认为对应对继发性感染是有害的。在这里，我们的特点细菌重编程的PBMC来源的单核细胞，特别关注其吞噬活性。因此，我们已经实施了一个替代模型的早期，炎症后的时期，暴露PBMC大肠杆菌的第0天，并重新挑战他们与细菌的第2天。这诱导了一种独特的单核细胞表型的出现，具有显著的吞噬功能障碍，但保留了幼稚T细胞刺激的能力。对吞噬作用的损害作用需要细菌的存在，并且不能通过TLR 4连接或单独暴露于分离的细胞因子来模拟。此外，损伤是特异性的吞噬细菌，并耦合到一个选择性下调Fc γ R和SR的表达。有趣的是，这种单核细胞表型有助于在继发感染的背景下刺激T（H）17极化的适应性免疫应答。我们的研究结果扩展了目前对单核细胞重编程的认识，并将单核细胞的吞噬能力确定为假定的脓毒症生物标志物。J. Leukoc. 91：977-989; 2012.
Septic diseases are characterized by an initial systemic, proinflammatory phase, followed by a period of anti-inflammation. In the context of the latter, monocytes have been described to display altered functions, including reduced TNF secretion and T cell-stimulating capacities in response to recall antigens. This hyporesponsiveness is supposed to be detrimental for coping with secondary infections. We here characterize bacterially reprogrammed PBMC-derived monocytes with special focus on their phagocytic activity. Hence, we have implemented a surrogate model of the early, postinflammatory period by exposing PBMCs to Escherichia coli on d0 and rechallenging them with bacteria on d2. This induced the emergence of a distinct monocytic phenotype with profound phagocytic impairments but a preserved ability for naive T cell stimulation. The compromising effects on phagocytosis required the presence of bacteria and were not mimicked by TLR4 ligation or exposure to isolated cytokines alone. Moreover, the impairments were specific for the engulfment of bacteria and were coupled to a selective down-regulation of Fc gamma R and SR expression. Intriguingly, this monocytic phenotype contributed to the stimulation of a T(H)17-polarized adaptive immune response in the context of secondary infection. Our findings extend the current knowledge of monocytic reprogramming and identify the phagocytic capacity of monocytes as a putative sepsis biomarker. J. Leukoc. Biol. 91: 977-989; 2012.