Macrophage Protein Disulfide Isomerase Increases Infection by Leishmania amazonensis

Area of Science:

• Immunology
• Parasitology
• Cell Biology

Background:

• Leishmania spp. cause leishmaniasis, with L. amazonensis being a prevalent dermotropic species in Brazil.
• Macrophage phagocytosis is crucial for Leishmania infection, involving various cell surface proteins.
• Previous studies linked macrophage surface protein disulfide isomerase (PDI) to increased phagocytosis of Leishmania infantum.

Purpose of the Study:

• To investigate the role of surface protein disulfide isomerase (PDI) in macrophage phagocytosis and infection by Leishmania (L.) amazonensis.
• To evaluate the impact of PDI overexpression in transgenic mice on L. amazonensis infection dynamics.

Main Methods:

• Utilized transgenic FVB/NJ mice overexpressing PDI (TgPDIA1).
• Validated PDI presence on macrophages via flow cytometry.
• Assessed macrophage infection and zymosan particle uptake after PDI modulation (anti-PDI antibodies, PDI overexpression).
• Conducted in vivo imaging of infections in wild-type and TgPDIA1 mice using luciferase-expressing parasites.

Main Results:

• Antibody-mediated blockade of surface PDI reduced L. amazonensis infection in macrophages.
• Overexpression of PDI in macrophages increased parasite adhesion and subsequent infection.
• Macrophages overexpressing PDI exhibited enhanced uptake of zymosan particles.
• In vivo, PDI overexpression did not lead to significant differences in footpad lesions or parasite burden.

Conclusions:

• Surface PDI promotes L. amazonensis phagocytosis and infection of macrophages in vitro.
• The in vivo impact of PDI overexpression on Leishmania infection is complex and potentially masked by its widespread roles in the immune system.