Siddiqui Arif Jamal, Bhardwaj Jyoti, Goyal Manish, Prakash Kirtika, Adnan Mohd, Alreshidi Mousa M, Patel Mitesh, Soni Awakash, Redman Whitni
Department of Biology, College of Sciences, University of Ha'il, Ha'il, Saudi Arabia.
Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
J Adv Res. 2020 Feb 26;24:29-41. doi: 10.1016/j.jare.2020.02.016. eCollection 2020 Jul.
Though the immunity to malaria has been associated with cellular immune responses, the exact function of the phenotypic cell population is still unclear. This study investigated the host immune responses elicited during the pre-erythrocytic stage, post- sporozoite infection in Swiss mice model. For this purpose, we analyzed the dynamics of different subsets of immune cells population and cytokine levels in the hepatic mononuclear and splenic cells population during pre-erythrocytic liver-stage infection. We observed a significant reduction in the effectors immune cells population including CD8 T cell, F4/80 macrophage and in plasmacytoid dendritic cells (CD11c B220). Interestingly, substantial down-regulation was also noted in pro-inflammatory cytokines (i.e. IFN-γ, TNF-α, IL-12, IL-2, IL-17 and iNOS), while, up-regulation of anti-inflammatory cytokines (i.e. IL-10, IL-4 and TGF-β) during asymptomatic pre-erythrocytic liver-stage infection. Collectively, this study demonstrated that during pre-erythrocytic development, sporozoite impaired the host activators of innate and adaptive immune responses by regulating the immune effector cells, gene expression and cytokines levels for the establishment of infection and subsequent development in the liver and spleen. The results in this study provided a better understanding of the events leading to malarial infection and will be helpful in supportive treatment and vaccine development strategy.
尽管对疟疾的免疫与细胞免疫反应有关,但表型细胞群体的确切功能仍不清楚。本研究在瑞士小鼠模型中调查了子孢子感染后红细胞前期阶段引发的宿主免疫反应。为此,我们分析了红细胞前期肝脏阶段感染期间肝单核细胞和脾细胞群体中不同免疫细胞亚群的动态变化以及细胞因子水平。我们观察到包括CD8 T细胞、F4/80巨噬细胞和浆细胞样树突状细胞(CD11c B220)在内的效应免疫细胞群体显著减少。有趣的是,在无症状的红细胞前期肝脏阶段感染期间,促炎细胞因子(即IFN-γ、TNF-α、IL-12、IL-2、IL-17和iNOS)也出现了显著下调,而抗炎细胞因子(即IL-10、IL-4和TGF-β)则上调。总体而言,本研究表明,在红细胞前期发育过程中,子孢子通过调节免疫效应细胞、基因表达和细胞因子水平,损害了宿主先天性和适应性免疫反应的激活因子,从而在肝脏和脾脏中建立感染并随后发展。本研究结果有助于更好地理解导致疟疾感染的事件,并将有助于支持性治疗和疫苗开发策略。