Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Belo Horizonte, MG, Brasil.
Universidade de São Paulo, Faculdade de Medicina, Departamento de Patologia, Laboratório de Patologia de Moléstias Infecciosas, São Paulo, SP, Brasil.
Mem Inst Oswaldo Cruz. 2020 Sep 21;115:e200140. doi: 10.1590/0074-02760200140. eCollection 2020.
Although Leishmania infantum is well-known as the aethiological agent of visceral leishmaniasis (VL), in some Central American countries it may cause atypical non-ulcerated cutaneous leishmaniasis (NUCL). However, the mechanisms favoring its establishment in the skin are still unknown. Lipophosphoglycan (LPG) is the major Leishmania multivirulence factor involved in parasite-host interaction. In the case of viscerotropic L. infantum, it causes an immunosuppression during the interaction with macrophages. Here, we investigated the biochemical and functional roles of LPGs from four dermotropic L. infantum strains from Honduras during in vitro interaction with murine macrophages. LPGs were extracted, purified and their repeat units analysed. They did not have side chains consisting of Gal(β1,4)Man(α1)-PO4 common to all LPGs. Peritoneal macrophages from BALB/c and C57BL/6 were exposed to LPG for nitric oxide (NO) and cytokine (TNF-α and, IL-6) production. LPGs from dermotropic strains from Honduras triggered higher NO and cytokine levels compared to those from viscerotropic strains. In conclusion, LPGs from dermotropic strains are devoid of side-chains and exhibit high pro-inflammatory activity.
虽然利什曼原虫是内脏利什曼病(VL)的已知病原体,但在一些中美洲国家,它可能导致非溃疡性皮肤利什曼病(NUCL)。然而,有利于其在皮肤中建立的机制尚不清楚。脂磷壁酸(LPG)是参与寄生虫与宿主相互作用的主要利什曼多毒力因子。在亲内脏的利什曼原虫的情况下,它在与巨噬细胞相互作用时引起免疫抑制。在这里,我们研究了来自洪都拉斯的四种亲皮利什曼原虫株与小鼠巨噬细胞体外相互作用时的 LPG 的生化和功能作用。提取、纯化了 LPG 并分析了它们的重复单位。它们没有侧链,这些侧链由所有 LPG 共有的 Gal(β1,4)Man(α1)-PO4 组成。BALB/c 和 C57BL/6 的腹腔巨噬细胞暴露于 LPG 以产生一氧化氮(NO)和细胞因子(TNF-α 和 IL-6)。与亲内脏菌株相比,来自洪都拉斯亲皮菌株的 LPG 触发了更高水平的 NO 和细胞因子。总之,亲皮菌株的 LPG 没有侧链,表现出很高的促炎活性。
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