Babesia divergens glycosylphosphatidylinositols modulate blood coagulation and induce Th2-biased cytokine profiles in antigen presenting cells
Babesia divergens glycosylphosphatidylinositols modulate blood coagulation and induce Th2-biased cytokine profiles in antigen presenting cells
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DOI：
10.1016/j.biochi.2019.09.007
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发表时间：
2019-12-01
期刊：
影响因子：
3.9
通讯作者：
Cornillot, Emmanuel
中科院分区：
文献类型：
--
作者：
Debierre-Grockiego, Francoise;Smith, Terry K.;Cornillot, Emmanuel
糖基磷脂酰肌醇（GPIs）是一种糖脂，由于其在哺乳动物宿主中的炎症特性，被描述为原生动物寄生虫的毒素，其特征在于产生白细胞介素（IL）-1，IL-12和肿瘤坏死因子（THF）-α。在目前的工作中，我们研究了由抗原呈递细胞产生的细胞因子，以响应从巴贝斯虫病中提取的10种不同的GPI。有趣的是，B。趋异因子GPIs诱导巨噬细胞和树突状细胞产生抗炎细胞因子（IL-2、IL-5）和调节细胞因子IL-10。与迄今为止研究的所有原生动物GPIs相反，来自B.趋异因子不刺激THF-alpha和IL-12的产生，导致独特的Th 1/Th 2分布。分析B的碳水化合物组成。分歧者GPIs表明二甘露糖结构不同于进化上保守的三甘露糖结构，这可能解释了它们诱导的特定细胞因子谱。树突状细胞主要组织相容性复合物（MHC）分子的表达和小鼠腹腔细胞凋亡也进行了分析。B。趋异基因GPIs不改变MHC I类分子的表达，但降低了细胞表面MHC II类分子的表达，而GPIs轻微增加了凋亡细胞的百分比。在巴贝斯虫病的发病过程中，炎症-凝血自放大环可导致血栓形成，并研究了GPIs对凝血参数的影响。B的孵育。divergens GPIs与大鼠血浆离体导致纤维蛋白原水平的增加和活化部分凝血活酶时间的延长，表明GPIs对外源性凝血途径的直接调节。(C)2019年，任作家。由爱思唯尔公司出版
Glycosylphosphatidylinositols (GPIs) are glycolipids described as toxins of protozoan parasites due to their inflammatory properties in mammalian hosts characterized by the production of interleukin (IL)-1, IL-12 and tumor necrosis factor (THF)-alpha. In the present work, we studied the cytokines produced by antigen presenting cells in response to ten different GPI species extracted from Babesia divergens, responsible for babesiosis. Interestingly, B. divergens GPIs induced the production of anti-inflammatory cytokines (IL-2, IL-5) and of the regulatory cytokine IL-10 by macrophages and dendritic cells. In contrast to all protozoan GPIs studied until now, GPIs from B. divergens did not stimulate the production of THF-alpha and IL-12, leading to a unique Th1/Th2 profile. Analysis of the carbohydrate composition of the B. divergens GPIs indicated that the di-mannose structure was different from the evolutionary conserved tri-mannose structure, which might explain the particular cytokine profile they induce. Expression of major histocompatibility complex (MHC) molecules on dendritic cells and apoptosis of mouse peritoneal cells were also analysed. B. divergens GPIs did not change expression of MHC class I, but decreased expression of MHC class II at the cell surface, while GPIs slightly increased the percentages of apoptotic cells. During pathogenesis of babesiosis, the inflammation-coagulation auto-amplification loop can lead to thrombosis and the effect of GPIs on coagulation parameters was investigated. Incubation of B. divergens GPIs with rat plasma ex vivo led to increase of fibrinogen levels and to prolonged activated partial thromboplastin time, suggesting a direct modulation of the extrinsic coagulation pathway by GPIs. (C) 2019 The Authors. Published by Elsevier B.V.