Thakur Ajit K, Purkait Bidyut, Jamal Fauzia, Singh Manish K, Ahmed Ghufran, Bimal Sanjiva, Kumar Vijay, Singh Subhankar K, Keshri Srikant, Das Pradeep, Narayan Shyam
Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agam Kuan, Patna 800 007, India.
Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agam Kuan, Patna 800 007, India.
Cytokine. 2016 Oct;86:79-85. doi: 10.1016/j.cyto.2016.07.017. Epub 2016 Jul 30.
Currently the main concerns regarding control of visceral leishmaniasis (VL) caused by L. donovani are immunosuppression, relating toxicity of anti-leishmanial drug and little development in appropriate vaccine and vector (P. argentipes) control. Reports available from ex-vivo studies reflect significance of vector salivary gland homogenate (SGH) in reverting immunosuppression of infected VL subjects and as such the immunogenic nature of SGH can be a strategy to modulate immune system and anti-leishmanial function to enable immune response to control the disease. Several related studies also identified a better utility of vector anti-saliva antibodies in achieving such effects by an adoptive transfer approach instead of direct stimulation with SGH protein. However, conclusive evidences on VL cases are far beyond satisfactory to suggest role of SGH into modulation of host immune response in VL subjects in India. This study was under taken to make comparison on change in cytokines (TH1 and TH2) response pattern and anti-leishmanial macrophage (Mϕ) function following stimulation of their PBMCS with SGH protein derived from P. argentipes sand fly vector for VL or anti SGH antibodies raised in rabbit. This study reports for the first time that L. donovani sensitized healthy subject demonstrates an up-regulated Interferon-γ (TH1) and down regulate Interleukin-10 (TH2) production following stimulation of their PBMCs by P. argentipes anti-saliva antibodies accompanied with an improvement in anti-leishmanial Mϕ function for nitric oxide (NO) production. Subsequent experiments suggest that P. argentipes based anti-SGH antibodies when used to stimulate LD infected PBMCs in healthy subjects resulted in better clearance of Leishmania amastigotes load compare to SGH protein. Possibly the immunogenic components of anti-saliva an antibody maintains the level of protective cytokine (INF-γ) and seems to restrict the infection by host protection by vector saliva.
目前，关于杜氏利什曼原虫引起的内脏利什曼病（VL）控制的主要问题包括免疫抑制、抗利什曼药物的相关毒性，以及在合适疫苗和病媒（银足按蚊）控制方面进展甚微。体外研究的现有报告反映了病媒唾液腺匀浆（SGH）在逆转感染VL患者免疫抑制方面的重要性，因此SGH的免疫原性本质可以成为一种调节免疫系统和抗利什曼功能以促使免疫反应控制疾病的策略。多项相关研究还发现，通过过继转移方法而非用SGH蛋白直接刺激，病媒抗唾液抗体在实现此类效果方面具有更好的效用。然而，关于VL病例的确凿证据远未达到令人满意的程度，不足以表明SGH在调节印度VL患者宿主免疫反应中的作用。本研究旨在比较用来自VL病媒银足按蚊的SGH蛋白或兔体内产生的抗SGH抗体刺激其外周血单核细胞（PBMC）后细胞因子（TH1和TH2）反应模式的变化以及抗利什曼巨噬细胞（Mϕ）功能。本研究首次报告，用银足按蚊抗唾液抗体刺激杜氏利什曼原虫致敏的健康受试者的PBMC后，干扰素-γ（TH1）产生上调，白细胞介素-10（TH2）产生下调，同时抗利什曼Mϕ产生一氧化氮（NO）的功能得到改善。后续实验表明，与SGH蛋白相比，用基于银足按蚊的抗SGH抗体刺激健康受试者中感染杜氏利什曼原虫的PBMC时，利什曼无鞭毛体负荷的清除效果更好。抗唾液抗体的免疫原性成分可能维持了保护性细胞因子（INF-γ）的水平，并且似乎通过宿主对病媒唾液的保护作用来限制感染。
