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Leishmania infantum and Leishmania braziliensis: Differences and Similarities to Evade the Innate Immune System

机译:婴儿利什曼原虫巴西利什曼原虫:逃避先天免疫系统的异同

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Visceral leishmaniasis is a severe form of the disease, caused by Leishmania infantum in the New World. Patients present an anergic immune response that favors parasite establishment and spreading through tissues like bone marrow and liver. On the other hand, Leishmania braziliensis causes localized cutaneous lesions, which can be self-healing in some individuals. Interactions between host and parasite are essential to understand disease pathogenesis and progression. In this context, dendritic cells (DCs) act as essential bridges that connect innate and adaptive immune responses. In this way, the aim of this study was to compare the effects of these two Leishmania species, in some aspects of human DCs’ biology for better understanding of the evasion mechanisms of Leishmania from host innate immune response. To do so, DCs were obtained from monocytes from whole peripheral blood of healthy volunteer donors and from those infected with L. infantum or L. braziliensis for 24?h. We observed similar rates of infection (around 40%) as well as parasite burden for both Leishmania species. Concerning surface molecules, we observed that both parasites induced CD86 expression when DCs were infected for 24?h. On the other hand, we detected a lower surface expression of CD209 in the presence of both L. braziliensis and L. infantum , but only the last one promoted the survival of DCs after 24?h. Therefore, DCs infected by both Leishmania species showed a higher expression of CD86 and a decrease of CD209 expression, suggesting that both enter DCs through CD209 molecule. However, only L. infantum had the ability to inhibit DC apoptotic death, as an evasion mechanism that enables its spreading to organs like bone marrow and liver. Lastly, L. braziliensis was more silent parasite, once it did not inhibit DC apoptosis in our in vitro model.
机译:内脏利什曼病是一种严重的疾病,由新世界的婴儿利什曼原虫引起。患者表现出有利于寄生虫建立并通过诸如骨髓和肝等组织传播的无性免疫反应。另一方面,巴西利什曼原虫引起局部皮肤损伤,在某些个体中可以自我修复。宿主与寄生虫之间的相互作用对于了解疾病的发病机理和进展至关重要。在这种情况下,树突状细胞(DC)充当连接先天性和适应性免疫反应的重要桥梁。这样,本研究的目的是在人类DC生物学的某些方面比较这两种利什曼原虫物种的作用,以更好地了解利什曼原虫从宿主固有免疫反应中逃逸的机制。为此,从健康志愿者捐献者全外周血中的单核细胞以及感染婴儿乳杆菌或巴西乳杆菌24 h的单核细胞获得DC。我们观察到两种利什曼原虫物种的感染率相似(约40%)以及寄生虫负担。关于表面分子,我们观察到DC感染24小时后,两种寄生虫均诱导CD86表达。另一方面,我们在巴西乳杆菌和婴儿乳杆菌的存在下检测到CD209的表面表达较低,但是只有最后一个在24小时后才促进DC的存活。因此,被两种利什曼原虫感染的DC显示出较高的CD86表达和CD209表达的降低,表明两者都通过CD209分子进入DC。但是,只有婴儿乳杆菌才具有抑制DC细胞凋亡死亡的能力,这是一种逃避机制,可以使其扩散到骨髓和肝脏等器官。最后,一旦在我们的体外模型中巴西乳杆菌不抑制DC凋亡,它就更是沉默的寄生虫。

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