Department of Medical Parasitology and Mycology, Kerman University of Medical Sciences, Kerman, Iran.
Leishmaniasis Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Microb Pathog. 2019 Jan;126:368-378. doi: 10.1016/j.micpath.2018.11.004. Epub 2018 Nov 3.
Detection of the mechanism of host/parasite interactions in unresponsive forms of anthroponotic cutaneous leishmaniasis (ACL) caused by Leishmania tropica is helpful for immunotherapy and vaccine development. In the present study, the gene expression of toll-like receptors (TLRs), TNF-α, iNOS and also arginase (ARG) activity in monocytes from Glucantime unresponsive in comparison to responsive patients infected with L. tropica was investigated.
In this case-control study, patients with unresponsive (n = 10) and responsive (n = 10) ACL were recruited. Gene expression of TLR2, TLR4, TLR9, TNF-α and iNOS was analyzed in L. tropica-exposed monocytes. The level of ARG activity in both isolated promastigotes and the lysates of monocytes was also determined.
L. tropica-exposed monocytes represented higher expression of all three TLRs and TNF-α and lower expression of iNOS compared to unexposed ones in both groups of patients. Results revealed a significant down-regulation of TLR2 and TNF-α and up-regulation of TLR9 expression in unresponsive isolates in comparison to responsive ones. Besides, ARG level showed a significant increase in L. tropica-stimulated monocytes and cultured promastigotes from unresponsive isolates versus responsive ones.
The decreased TLR2, TLR4, TNF-α and iNOS and the increased level of TLR9 expression in L. tropica-exposed monocytes from unresponsive isolates and also the increment in ARG activity in their promastigotes and monocytes, might possibly be involved in the severity of the disease and leading to Glucantime unresponsiveness.
检测利什曼原虫（Leishmania tropica）引起的无反应性人源皮肤利什曼病（ACL）中宿主/寄生虫相互作用的机制有助于免疫治疗和疫苗的开发。在本研究中，我们研究了与利什曼原虫感染的 Glucantime 无反应患者相比，无反应患者（n=10）和反应患者（n=10）单核细胞中 toll 样受体（TLRs）、TNF-α、iNOS 的基因表达以及精氨酸酶（ARG）的活性。
在这项病例对照研究中，招募了无反应（n=10）和反应（n=10）ACL 患者。分析了 TLR2、TLR4、TLR9、TNF-α 和 iNOS 在利什曼原虫暴露的单核细胞中的表达。还测定了两种细胞（分离的前鞭毛体和单核细胞的裂解物）中 ARG 活性的水平。
与未暴露的单核细胞相比，两组患者中，利什曼原虫暴露的单核细胞均表现出所有三种 TLR 和 TNF-α的高表达，以及 iNOS 的低表达。结果显示，与反应性分离株相比，无反应性分离株中 TLR2 和 TNF-α的表达显著下调，TLR9 的表达上调。此外，与反应性分离株相比，无反应性分离株中利什曼原虫刺激的单核细胞和培养的前鞭毛体中的 ARG 水平显著增加。
无反应性分离株中利什曼原虫暴露的单核细胞中 TLR2、TLR4、TNF-α 和 iNOS 的表达下调，TLR9 的表达上调，以及其前鞭毛体和单核细胞中 ARG 活性的增加，可能与疾病的严重程度有关，并导致 Glucantime 无反应性。
