Immunomodulatory Properties of Leishmania Extracellular Vesicles During Host-Parasite Interaction: Differential Activation of TLRs and NF-κB Translocation by Dermotropic and Viscerotropic Species
Immunomodulatory Properties of Leishmania Extracellular Vesicles During Host-Parasite Interaction: Differential Activation of TLRs and NF-κB Translocation by Dermotropic and Viscerotropic Species
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DOI：
10.3389/fcimb.2020.00380
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发表时间：
2020-07-29
影响因子：
5.7
通讯作者：
Soares, Rodrigo Pedro
中科院分区：
文献类型：
--
作者：
Nogueira, Paula Monalisa;de Menezes-Neto, Armando;Soares, Rodrigo Pedro
利什曼病毒感染会导致相当大的人类发病率，并可能在流行地区发展为致命的内脏形式。这种寄生虫感染巨噬细胞，在那里它们可以在细胞内复制。此外，它们通过使用毒力因子(脂多糖、糖蛋白-63等)调节宿主免疫反应，促进细胞内的存活。在致炎环境中，寄生虫释放的胞外小泡(EV)对细胞间的通讯起着重要的作用，调节感染的发生。然而，关于来自不同利什曼亚种的EV调节炎症反应的能力的信息很少，特别是那些引起不同临床表现(内脏和皮肤)的物种。这项研究的目的是比较来自新大陆的三种利什曼原虫EVS对巨噬细胞的激活作用。Infantum、巴西乳杆菌(L.braziliensis)和乳杆菌(L.亚马逊人。在小鼠巨噬细胞暴露之前，将EV从前鞭毛体中释放出来，通过超速离心法纯化，并通过纳米颗粒跟踪分析(NTA)进行定量。NTA分析表明，不同菌株之间的EV大小没有任何差异。电动汽车从毫升。巴西和L。婴儿期未能引发促炎反应。来自两家公司的电动汽车。婴儿WT和LPG缺失突变体(LPG-KO)在与巨噬细胞的相互作用方面没有表现出任何差异，表明LPG单独不是激活的决定因素。另一方面，电动汽车FROML。其免疫调节作用主要是通过TLR4和TLR2产生NO、TNF-α、IL-6和IL-10。为了确定这种激活是否与核因子-kappa B p65易位有关，将THP-1巨噬细胞暴露于EV。以同样的方式，只有电动汽车FROML。我们的结果表明，EVS在决定免疫反应模式方面发挥着重要作用，这取决于寄生虫的种类。Forl.Inantum认为，液化石油气不是激活的决定因素。
Leishmaniainfection causes considerable human morbidity and may develop into a deadly visceral form in endemic regions. The parasite infects macrophages where they can replicate intracellularly. Furthermore, they modulate host immune responses by using virulence factors (lipophosphoglycan, glycoprotein-63, and others) that promote survival inside the cells. Extracellular vesicles (EVs) released by parasites are important for cell-cell communication in the proinflammatory milieu modulating the establishment of infection. However, information on the ability of EVs from differentLeishmaniaspecies to modulate inflammatory responses is scarce, especially from those species causing different clinical manifestations (visceral vs. cutaneous). The purpose of this study was to compare macrophage activation using EVs from threeLeishmaniaspecies from New World includingL. infantum, L. braziliensis, andL. amazonensis. EVs were released from promastigote forms, purified by ultracentrifugation and quantitated by Nanoparticle Tracking Analysis (NTA) prior to murine macrophage exposure. NTA analysis did not show any differences in the EV sizes among the strains. EVs fromL. braziliensisandL. infantumfailed to induce a pro-inflammatory response. EVs from bothL. infantumWT and LPG-deficient mutant (LPG-KO) did not show any differences in their interaction with macrophages, suggesting that LPG solely was not determinant for activation. On the other hand, EVs fromL. amazonensiswere immunomodulatory inducing NO, TNF-alpha, IL-6, and IL-10 via TLR4 and TLR2. To determine whether such activation was related to NF-kappa B p65 translocation, THP-1 macrophage cells were exposed to EVs. In the same way, only EVs fromL. amazonensisexhibited a highly percentage of cells positive for NF-kappa B. Our results suggest an important role of EVs in determining the pattern of immune response depending on the parasite species. ForL. infantum, LPG was not determinant for the activation.