Activation of apoptosis, but not necrosis, during Mycobacterium tuberculosis infection correlated with decreased bacterial growth:: Role of TNF-α, IL-10, caspases and phospholipase A2
Activation of apoptosis, but not necrosis, during Mycobacterium tuberculosis infection correlated with decreased bacterial growth:: Role of TNF-α, IL-10, caspases and phospholipase A2
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DOI：
10.1016/j.cellimm.2007.11.006
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发表时间：
2007-10-01
影响因子：
4.3
通讯作者：
Rojas, Mauricio
中科院分区：
文献类型：
--
作者：
Arcila, Mary Luz;Sanchez, Maria Dulfary;Rojas, Mauricio
单核细胞/巨噬细胞死亡是分枝杆菌感染过程中的一个重要事件。为了深入了解单核吞噬细胞成熟在这一事件中的影响，我们比较了来自健康结核菌素阳性个体的新鲜分离单核细胞和单核细胞源性巨噬细胞（MDM）对结核分枝杆菌（Mtb）感染的反应。单核细胞和MDM均发生凋亡，但凋亡的巨噬细胞数量较多，Caspases 8和9具有活性。我们还比较了mmb诱导的U937前单核细胞和pma分化细胞（U937D）的细胞死亡。Mtb感染后，U937D细胞发生凋亡，单核细胞发生凋亡和坏死。大量的U937D细胞产生tnf - α和大量的IL-10（+）原细胞。这些证据表明，U937可能是研究mmb诱导细胞死亡机制的有效模型。用药理学抑制剂对细胞系和新鲜分离的单核细胞进行的实验表明，坏死的诱导涉及钙和cAMP信号，导致IL-10的产生。坏死还与Caspase 3、PLA2活性和细菌生长有关。在U937D细胞和来自健康供体的单核细胞中，钙、tnf - α和Caspase 8被激活，细菌负荷下降。了解与细胞成熟相关的细胞凋亡和坏死/肿瘤分化事件的控制机制，可能为更好地控制分枝杆菌感染的过程开辟新的策略。(C) 2007爱思唯尔公司版权所有。
Monocyte/macrophage cell death is an important event during mycobacterial infection. To get insights about the influence of mononuclear phagocyte maturation in this event we compared the response to Mycobacterium tuberculosis (Mtb) infection of fresh isolated monocytes and monocyte-derived macrophages (MDM) from healthy tuberculin positive individuals. Both monocytes and MDM underwent apoptosis, however, there was a higher numbers of apoptotic macrophages with active Caspases 8 and 9. We also compared Mtb-induced cell death in U937 pro-monocytes and PMA-differentiated cells (U937D). In response to Mtb infection, U937D cells underwent apoptosis and promonocytes both apoptosis and necrosis. There were high number of U937D cells producing TNF-alpha and high number of IL-10(+) promonocytes. These evidences suggest that U937 could be a valid model to study the mechanisms that rule Mtb-induced cell death. Experiments with the cell line and fresh isolated mononuclear cells with pharmacological inhibitors showed that induction of necrosis involved calcium and cAMP signals resulting in IL-10 production. Necrosis also correlated with Caspase 3, PLA2 activity and bacterial growth. In U937D cells and monocytes from healthy donors there was activation of calcium, TNF-alpha and Caspase 8 activation and decreased bacterial load. Understanding the mechanisms that control the dichotomy events between apoptosis and necrosis/ oncosis associated with cell maturity might open new strategies to better control the course of mycobacterial infections. (C) 2007 Elsevier Inc. All rights reserved.