Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz - FIOCRUZ, Belo Horizonte, Brazil.
PLoS Negl Trop Dis. 2012;6(2):e1543. doi: 10.1371/journal.pntd.0001543. Epub 2012 Feb 28.
The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important South American species Leishmania infantum and L. braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL), respectively. GIPLs derived from both species did not induce NO or TNF-α production by non-primed murine macrophages. Additionally, primed macrophages from mice (BALB/c, C57BL/6, TLR2-/- and TLR4-/-) exposed to GIPLs from both species, with exception to TNF-α, did not produce any of the cytokines analyzed (IL1-β, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-γ) or p38 activation. GIPLs induced the production of TNF-α and NO by C57BL/6 mice, primarily via TLR4. Pre incubation of macrophages with GIPLs reduced significantly the amount of NO and IL-12 in the presence of IFN-γ or lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs. This inhibition was reversed after PI-specific phospholipase C treatment. A structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs, suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in the structure and composition of GIPLs from L. braziliensis and L. infantum. Also, GIPLs are important inhibitory molecules during the interaction with macrophages.
脂磷壁酸（LPG）在利什曼原虫固有免疫反应中的重要作用已被广泛报道。然而，有关 LPG 相关糖基肌醇磷脂（GIPL）的信息有限，特别是在新世界利什曼原虫物种方面。GIPL 是覆盖寄生虫表面的低分子量分子，与 LPG 相似，具有共同的脂质主链和含有多达 7 个糖的糖基基序。它们在与脊椎动物宿主相互作用中的结构和功能的关键方面仍然不清楚。在这项研究中，我们评估了这些分子在两种医学上重要的南美物种利什曼原虫婴儿和利什曼原虫巴西利什曼原虫中的作用，它们分别是内脏利什曼病（VL）和皮肤利什曼病（CL）的病原体。两种物种衍生的 GIPL 均不能诱导非初免的鼠巨噬细胞产生 NO 或 TNF-α。此外，暴露于两种物种的 GIPL 的经初免的巨噬细胞（BALB/c、C57BL/6、TLR2-/-和 TLR4-/-）除 TNF-α外，均未产生分析的任何一种细胞因子（IL1-β、IL-2、IL-4、IL-5、IL-10、IL-12p40、IFN-γ）或 p38 激活。GIPL 通过 TLR4 诱导 C57BL/6 小鼠产生 TNF-α和 NO。巨噬细胞与 GIPL 预孵育后，在存在 IFN-γ或脂多糖（LPS）的情况下，NO 和 IL-12 的量明显减少，用 L. braziliensis GIPL 更为明显。在用 PI 特异性磷脂酶 C 处理后，这种抑制被逆转。GIPL 的结构分析表明，L. infantum 具有富含甘露糖的 GIPL，提示为 I 型和混合 GIPL，而 L. braziliensis 具有富含半乳糖的 GIPL，提示为 II 型 GIPL。总之，L. braziliensis 和 L. infantum 的 GIPL 在结构和组成上存在很大差异。此外，GIPL 是与巨噬细胞相互作用过程中的重要抑制分子。
