The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of Leishmania braziliensis by Monocytes from Patients with Cutaneous Leishmaniasis
The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of Leishmania braziliensis by Monocytes from Patients with Cutaneous Leishmaniasis
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DOI：
10.1371/journal.pone.0148084
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发表时间：
2016-02-03
期刊：
影响因子：
3.7
通讯作者：
Bacellar, Olivia
中科院分区：
文献类型：
--
作者：
Carneiro, Pedro Paulo;Conceicao, Jacilara;Bacellar, Olivia
由巴西利什曼原虫引起的人类皮肤利什曼病（CL）表现出与溃疡发展相关的过度Th1应答。巨噬细胞是利什曼原虫感染的主要细胞，活性氧（ROS）和一氧化氮（NO）在这些细胞对利什曼原虫的控制中起重要作用。对L. Braziliensis还没有很好地建立起来。在这项研究中，我们评估的作用，ROS和NO在控制L。来自CL患者的单核细胞的巴西人感染。体外感染L.巴西人中，与来自健康受试者（HS）的单核细胞相比，来自CL患者的单核细胞的氧化爆发更高。ROS途径的抑制导致L. braziliensis感染来自两组的单核细胞。此外，我们还检测了L.巴西人感染的单核细胞。CL患者单核细胞感染L.巴西。CL患者单核细胞中NO的表达高于HS患者单核细胞中NO的表达。CL患者的NO产生与病变大小呈显著正相关。抑制来自CL患者的利什曼原虫感染的单核细胞中的ROS产生允许培养上清液中的活前鞭毛体的生长。因此，我们证明，虽然生产的活性氧参与L。尽管在巴西线虫杀灭中，单独的NO不足以控制感染，并且可能导致在人CL中观察到的组织损伤。
Human cutaneous leishmaniasis (CL) caused by Leishmania braziliensis, presents an exaggerated Th1 response that is associated with ulcer development. Macrophages are the primary cells infected by Leishmania parasites and both reactive oxygen species (ROS) and nitric oxide (NO) are important in the control of Leishmania by these cells. The mechanism involved in the killing of L. braziliensis is not well established. In this study, we evaluate the role of ROS and NO in the control of L. braziliensis infection by monocytes from CL patients. After in vitro infection with L. braziliensis, the oxidative burst by monocytes from CL patients was higher when compared to monocytes from healthy subjects (HS). Inhibition of the ROS pathway caused a significant decrease in the oxidative burst in L. braziliensis infected monocytes from both groups. In addition, we evaluated the intracellular expression of ROS and NO in L. braziliensis-infected monocytes. Monocytes from CL patients presented high expression of ROS after infection with L. braziliensis. The expression of NO was higher in monocytes from CL patients as compared to expression in monocytes from HS. A strong positive correlation between NO production and lesion size of CL patients was observed. The inhibition of ROS production in leishmania-infected monocytes from CL patients allowed the growth of viable promastigotes in culture supernatants. Thus, we demonstrate that while production of ROS is involved in L. braziliensis killing, NO alone is not sufficient to control infection and may contribute to the tissue damage observed in human CL.