title: Lysosomal integral membrane protein 2 (LIMP-2) restricts the invasion of Trypanosoma cruzi extracellular amastigotes through the activity of the lysosomal enzyme β-glucocerebrosidase.
abstract: 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.
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
authors.forename: Viviane Martinelli
authors.initials: VM
authors.lastname: Gonçalves
authors.affiliation: Department of Psychobiology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: D'Almeida
authors.affiliation: Department of Pediatrics, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
authors.forename: Karen Barbosa
authors.initials: KB
authors.lastname: Müller
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil. Electronic address: fernando.real@unifesp.br.
authors.forename: Fernando
authors.initials: F
authors.lastname: Real
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Escola Paulista de Medicina, UNIFESP, São Paulo, Brazil.
authors.forename: Renato Arruda
authors.initials: RA
authors.lastname: Mortara
mesh_terms: D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D005347:Fibroblasts / Q000737:chemistry / Q000378:metabolism / Q000469:parasitology; D005962:Glucosylceramidase / Q000276:immunology* / Q000378:metabolism*; D008018:Life Cycle Stages / Q000502:physiology*; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014349:Trypanosoma cruzi / Q000472:pathogenicity*
chemical_list: D018955:CD36 Antigens; D051907:Lysosomal Membrane Proteins; C489452:Scarb2 protein, mouse; D005962:Glucosylceramidase
keywords: Extracellular amastigotes; LIMP-2; Trypanosoma cruzi; β-Glucocerebrosidase