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一氧化氮和活性氧在皮肤利什曼病患者单核细胞杀伤巴西利什曼原虫中的作用

The Role of Nitric Oxide and Reactive Oxygen Species in the Killing of Leishmania braziliensis by Monocytes from Patients with Cutaneous Leishmaniasis.

作者信息

Carneiro Pedro Paulo, Conceição Jacilara, Macedo Michael, Magalhães Viviane, Carvalho Edgar M, Bacellar Olivia

机构信息

Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Universidade Federal da Bahia, Salvador, Bahia, Brazil.

Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais - INCT-DT (CNPq/MCT), Salvador, BA, Brazil.

出版信息

PLoS One. 2016 Feb 3;11(2):e0148084. doi: 10.1371/journal.pone.0148084. eCollection 2016.

DOI:10.1371/journal.pone.0148084
PMID:26840253
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4739692/
Abstract

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.

摘要

由巴西利什曼原虫引起的人类皮肤利什曼病（CL）呈现出一种与溃疡发展相关的过度Th1反应。巨噬细胞是被利什曼原虫寄生的主要细胞，活性氧（ROS）和一氧化氮（NO）在这些细胞控制利什曼原虫方面都很重要。杀死巴西利什曼原虫所涉及的机制尚未完全明确。在本研究中，我们评估了ROS和NO在CL患者单核细胞控制巴西利什曼原虫感染中的作用。体外感染巴西利什曼原虫后，与健康受试者（HS）的单核细胞相比，CL患者的单核细胞氧化爆发更高。抑制ROS途径导致两组感染巴西利什曼原虫的单核细胞氧化爆发显著降低。此外，我们评估了感染巴西利什曼原虫的单核细胞中ROS和NO的细胞内表达。CL患者的单核细胞在感染巴西利什曼原虫后呈现出较高的ROS表达。与HS的单核细胞相比，CL患者的单核细胞中NO的表达更高。观察到CL患者的NO产生与病变大小之间存在强正相关。抑制CL患者感染利什曼原虫的单核细胞中的ROS产生，会使培养上清液中活前鞭毛体生长。因此，我们证明虽然ROS的产生参与了巴西利什曼原虫的杀伤，但单独的NO不足以控制感染，并且可能导致人类CL中观察到的组织损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/170736e649b9/pone.0148084.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/dc4b869da38b/pone.0148084.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/ea343d0c2139/pone.0148084.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/2046a8e6543f/pone.0148084.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/ede57cd21887/pone.0148084.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/07895b62e536/pone.0148084.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/e255047d9956/pone.0148084.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/170736e649b9/pone.0148084.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/dc4b869da38b/pone.0148084.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/ea343d0c2139/pone.0148084.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/2046a8e6543f/pone.0148084.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/ede57cd21887/pone.0148084.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/07895b62e536/pone.0148084.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/e255047d9956/pone.0148084.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0d0b/4739692/170736e649b9/pone.0148084.g007.jpg

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本文引用的文献

[1]
Protective and pathological functions of CD8+ T cells in Leishmania braziliensis infection.

Infect Immun. 2015-3

[2]
A Defective Oxidative Burst and Impaired Antigen Presentation are Hallmarks of Human Visceral Leishmaniasis.

J Clin Immunol. 2015-1

[3]
The role of nitric oxide in the pathogenesis and severity of psoriasis.

Georgian Med News. 2014-9

[4]
Intermediate monocytes contribute to pathologic immune response in Leishmania braziliensis infections.

J Infect Dis. 2015-1-15

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SOD1 plasma level as a biomarker for therapeutic failure in cutaneous leishmaniasis.

J Infect Dis. 2014-2-7

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Human classical monocytes control the intracellular stage of Leishmania braziliensis by reactive oxygen species.

J Infect Dis. 2014-1-7

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PLGA nanoparticles loaded with KMP-11 stimulate innate immunity and induce the killing of Leishmania.

Nanomedicine. 2013-4-17

[9]
Leishmania expressed lipophosphoglycan interacts with Toll-like receptor (TLR)-2 to decrease TLR-9 expression and reduce anti-leishmanial responses.

Clin Exp Immunol. 2013-6

[10]
IL-17 mediates immunopathology in the absence of IL-10 following Leishmania major infection.

PLoS Pathog. 2013-3-21

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