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

• Published in: Experimental parasitology Vol. 216; p. 107939
• Main Authors: Ribeiro, H., Rocha, M.I., Castro, H., Macedo, M.F.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01.09.2020
• Subjects: Gaucher disease; Leishmania; Macrophage; β-glucocerebrosidase; Gaucher disease; β-glucocerebrosidase; Leishmania; Macrophage
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2020.107939

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-glucocerebrosidase inactivation. Parameters of infection, recorded immediately after phagocytosis, as well as 24 and 48 h later, revealed no noticeable differences in the infection parameters of CBE-treated macrophages relative to non-treated controls. We conclude that blocking β-glucocerebrosidase activity during contact with Leishmania does not interfere with the phagocytic capacity of macrophages and the early onset of leishmanicidal responses. [Display omitted] •Leishmania spp. are obligatory intracellular parasites of macrophages (MO).•MO are the main cells affected in Gaucher patients.•Gaucher disease is characterized by a defective activity of β-glucocerebrosidase.•Gaucher-like MO were generated by chemical inhibition of β-glucocerebrosidase.•Gaucher-like MO are proficient at phagocytosing and controlling Leishmania.