Lysosomal integral membrane protein 2 (LIMP-2) restricts the invasion of Trypanosoma cruzi extracellular amastigotes through the activity of the lysosomal enzyme beta-glucocerebrosidase

摘要

Lysosomal integral membrane protein 2 (LDM1P-2, SCARB2) is directly linked to beta-glucocerebrosidase enzyme (beta GC) and mediates the transport of this enzyme from the Golgi complex to lysosomes. Active beta GC cleaves the beta-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 beta GC measured in fibroblast extracts. Replacement of beta GC enzyme in LIMP-2 deficient fibroblasts restores the infectivity indices to those of WT cells in T cruzti invasion assays. Considering the participation of beta GC 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. (C) 2013 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.