Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
Department of Psychobiology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
Microbes Infect. 2014 Mar;16(3):253-60. doi: 10.1016/j.micinf.2013.11.004. Epub 2013 Nov 20.
Lysosomal integral membrane protein 2 (LIMP-2, SCARB2) is directly linked to β-glucocerebrosidase enzyme (βGC) and mediates the transport of this enzyme from the Golgi complex to lysosomes. Active βGC cleaves the β-glycosidic linkages of glucosylceramide, an intermediate in the metabolism of sphingoglycolipids, generating ceramide. In this study we used mouse embryonic fibroblasts (MEFs) deficient for LIMP-2 and observed that these cells were more susceptible to infection by extracellular amastigotes of the protozoan parasite Trypanosoma cruzi when compared to wild-type (WT) fibroblasts. The absence of LIMP-2 decreases the activity of βGC measured in fibroblast extracts. Replacement of βGC enzyme in LIMP-2 deficient fibroblasts restores the infectivity indices to those of WT cells in T. cruzi invasion assays. Considering the participation of βGC in the production of host cell ceramide, we propose that T. cruzi extracellular amastigotes are more invasive to cells deficient in this membrane component. These results contribute to our understanding of the role of host cell lysosomal components in T. cruzi invasion.
溶酶体整合膜蛋白 2（LIMP-2，SCARB2）直接与β-葡萄糖脑苷脂酶（βGC）相连，并介导该酶从高尔基体复合物向溶酶体的运输。活性βGC 可切割鞘糖脂代谢过程中的β-糖苷键，生成神经酰胺。在这项研究中，我们使用缺乏 LIMP-2 的小鼠胚胎成纤维细胞（MEFs），并观察到与野生型（WT）成纤维细胞相比，这些细胞更容易被原生动物寄生虫克氏锥虫的细胞外无鞭毛体感染。LIMP-2 的缺失会降低成纤维细胞提取物中βGC 的活性。在 LIMP-2 缺陷型成纤维细胞中替换βGC 酶可使 T. cruzi 入侵测定中的感染指数恢复至 WT 细胞的水平。考虑到βGC 参与宿主细胞神经酰胺的产生，我们提出克氏锥虫细胞外无鞭毛体更容易侵袭缺乏这种膜成分的细胞。这些结果有助于我们理解宿主细胞溶酶体成分在 T. cruzi 入侵中的作用。
