Chemical inhibition of β-glucocerebrosidase does not affect phagocytosis and early containment of Leishmania by murine macrophages.

Chemical inhibition of β-glucocerebrosidase does not affect phagocytosis and early containment of Leishmania by murine macrophages. Exp Parasitol. 2020 Jun 11;:107939 Authors: Ribeiro H, Rocha MI, Castro H, Macedo MF Abstract Gaucher disease is a lysosomal storage disease in which a genetic deficiency in β-glucocerebrosidase leads to the accumulation of glycosphingolipids in lysosomes. Macrophages are amongst the cells most severely affected in Gaucher disease patients. One phenotype associated with Gaucher macrophages is the impaired capacity to fight bacterial infections. Here, we investigate whether inhibition of β-glucocerebrosidase activity affects the capacity of macrophages to phagocytose and act on the early containment of human pathogens of the genus Leishmania. Towards our aim, we performed in vitro infection assays on macrophages derived from the bone marrow of C57BL/6 mice. To mimic Gaucher disease, macrophages were incubated with the β-glucocerebrosidase inhibitor, conduritol B epoxide (CBE), prior to contact with Leishmania. This treatment guaranteed that β-glucocerebrosidase was fully inhibited during the contact of macrophages with Leishmania, its enzymatic activity being progressively recovered along the 48 h that followed removal of the inhibitor. Infections were performed with L. amazonensis, L. infantum, or L. major, so as to explore potential species-specific responses in the context of β-glucocerebrosida...
Source: Experimental Parasitology - Category: Parasitology Authors: Tags: Exp Parasitol Source Type: research