Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
Rajendra Memorial Research Institute of Medical Sciences, Bihar, India.
Nutrition. 2014 Apr;30(4):449-58. doi: 10.1016/j.nut.2013.10.003. Epub 2013 Oct 14.
Malnutrition may be significant in the modulation of immune responses in visceral leishmaniasis (VL). Data on the relationship between malnutrition and innate immune response in VL are limited. The aim of this study was to examine the effect of malnutrition on the profile of innate immune functions of polymorphonuclear neutrophil granulocytes (PMNs) and monocytes through comparison of well-nourished and malnourished Indian patients with VL.
Forty individuals were enrolled comprising 20 active and untreated cases of VL and 20 non-VL individuals from the endemic region of Bihar, India. The patients with VL were segregated into two groups of 10 well-nourished and 10 malnourished participants. Patients' blood samples were directed against a crude Leishmania donovani extract (soluble leishmanial antigen) and phorbol 12-myristate-13-acetate plus ionomycin. The transendothelial cell adherence migration abilities of the PMNs and monocytes directed against these antigens were determined in whole-blood assays by flow cytometry. The chemokine (interleukin [IL]-8, macrophage inflammatory protein [MIP]-1 α) and cytokine support (tumor necrosis factor -α, interferon [IFN]-γ, IL-10), which could be significant in transendothelial cell migration, and efficacies of antileishmanial phagocytic function and reactive oxygen species (ROS) generation were also determined.
Severe hindrance in the adherence of innate immune cells to the endothelial wall due to Leishmania parasites, as revealed by decreased shedding of l-selectin (CD62 L) and down-regulation of CD11 b expression on the surface of the PMNs and monocytes, occurred in malnourished VL patients. The production of MIP-1 α and IL-8 in response to L. donovani antigen was reduced in malnourished patients. In contrast, malnutrition in VL patients significantly reduced the IFN-γ and TNF-α produced by these immune cells, whereas the levels of IL-10 were significantly elevated. Malnourished VL patients were observed with severely dysfunctional PMNs and monocytes in terms of ROS activity that could not be recovered by stimulation with L. donovani antigen.
Malnutrition linked to VL can be a decisive factor in the dynamics of L. donovani evasion of innate immune cell function in VL patients.
营养不良可能在内脏利什曼病（VL）的免疫反应调节中起重要作用。有关 VL 中营养不良与先天免疫反应之间关系的数据有限。本研究旨在通过比较营养良好和营养不良的印度 VL 患者，研究营养不良对多形核中性粒细胞（PMN）和单核细胞先天免疫功能特征的影响。
共纳入 40 名个体，包括 20 名活动性和未经治疗的 VL 患者和 20 名来自印度比哈尔邦流行地区的非 VL 个体。将 VL 患者分为两组，每组 10 名营养良好的患者和 10 名营养不良的患者。针对粗利什曼原虫 donovani 提取物（可溶性利什曼抗原）和佛波醇 12-肉豆蔻酸 13-乙酸酯加离子霉素，检测患者的血液样本。通过流式细胞术在全血测定中测定针对这些抗原的 PMN 和单核细胞的跨内皮细胞粘附迁移能力。还确定了对跨内皮细胞迁移可能有重要意义的趋化因子（白细胞介素[IL]-8、巨噬细胞炎症蛋白[MIP]-1α）和细胞因子支持（肿瘤坏死因子-α、干扰素[IFN]-γ、IL-10），以及抗利什曼原虫吞噬功能和活性氧（ROS）生成的功效。
由于利什曼原虫寄生虫的存在，导致 PMN 和单核细胞对内皮壁的固有免疫细胞粘附严重受阻，表现为 L-选择素（CD62L）脱落减少和 PMN 和单核细胞表面 CD11b 表达下调。营养不良的 VL 患者对 L. donovani 抗原的 MIP-1α和 IL-8 产生减少。相反，VL 患者的营养不良显著降低了这些免疫细胞产生的 IFN-γ和 TNF-α，而 IL-10 水平显著升高。营养不良的 VL 患者观察到 PMN 和单核细胞的 ROS 活性严重功能障碍，无法通过 L. donovani 抗原刺激恢复。
与 VL 相关的营养不良可能是 VL 患者利什曼原虫逃避固有免疫细胞功能动态的决定性因素。
