National Institute of Pathology (ICMR), Safdarjung Hospital Campus, New Delhi 110029, India.
BMC Immunol. 2013 Nov 22;14:52. doi: 10.1186/1471-2172-14-52.
The interaction between the Leishmania parasite and the host cell involves complex, multifaceted processes. The disease severity in cutaneous leishmaniasis (CL) is largely dependent on the causative species. Most of the information on immune responses in human CL is available with respect to L. major infection and is lacking for L. tropica species. In this study, we employed cytokine/chemokine/receptor membrane cDNA array to capture comprehensive picture of immuno-determinants in localized human tissue during L. tropica infection. Expression of selected molecules was evaluated by real time PCR in dermal lesion tissues at pre- and post treatment stages. Plasma IL-17 level was estimated by sandwich ELISA.
The cDNA array analysis identified several immuno-determinants in tissue lesions of Indian CL including cytokines (IFN-γ, TNF-α, IL-1β, IL-10, IL-13), chemokines (IL-8, CCL2, CCL3, CCL4) and apoptotic molecules (Fas, TRAIL, IRF-1). Elevated mRNA levels of Th17 (IL-17, IL-23 and RORγt) and Treg (CD25, CTLA-4 and Foxp3) markers were observed in lesion tissues of CL patients compared to the control group, which subsided post treatment. Plasma IL-17 levels were found to be significantly higher in CL samples compared to controls.
In addition to defining comprehensive immunological responses inside lesion tissues of CL patients, our study demonstrated the presence of Th17 and Treg cells in CL caused by L. tropica.
利什曼原虫与宿主细胞的相互作用涉及复杂的、多方面的过程。皮肤利什曼病(CL)的疾病严重程度在很大程度上取决于致病物种。大多数关于人类 CL 免疫反应的信息都可用于 L. major 感染,而对于 L. tropica 物种则缺乏。在这项研究中,我们采用细胞因子/趋化因子/受体膜 cDNA 阵列来捕获 L. tropica 感染时局部人类组织中的免疫决定因素的全貌。通过实时 PCR 在治疗前后的皮肤病变组织中评估选定分子的表达。通过夹心 ELISA 估计血浆 IL-17 水平。
cDNA 阵列分析鉴定了印度 CL 组织病变中的几种免疫决定因素,包括细胞因子(IFN-γ、TNF-α、IL-1β、IL-10、IL-13)、趋化因子(IL-8、CCL2、CCL3、CCL4)和凋亡分子(Fas、TRAIL、IRF-1)。与对照组相比,CL 患者病变组织中 Th17(IL-17、IL-23 和 RORγt)和 Treg(CD25、CTLA-4 和 Foxp3)标志物的 mRNA 水平升高,治疗后下降。与对照组相比,CL 样本中的血浆 IL-17 水平明显升高。
除了定义 CL 患者病变组织中的全面免疫反应外,我们的研究还证明了 Th17 和 Treg 细胞在 L. tropica 引起的 CL 中的存在。