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Leishmania major proteophosphoglycan is expressed by amastigotes and has an immunomodulatory effect on macrophage
1The Walter and Eliza Hall Institute of Medical Research, Victoria 3050, Australia.
Abstract:
Proteophosphoglycan (PPG) is a newly described mucin-like glycoprotein found on the surface of Leishmania major promastigotes and secreted in the culture supernatant. We show here that antigenically similar PPGs are present in several Leishmania species. PPG could also be detected on the surface of amastigotes and in small, parasite-free vesicles in infected macrophages. Because of the similarity of its carbohydrate chains to lipophosphoglycan, a parasite receptor for host macrophages, PPG was tested for binding to macrophages. PPG bound to macrophages and was internalized in a time-dependent manner. PPG inhibited the production of tumor necrosis factor-alpha and synergized with interferon-gamma to stimulate the production of nitric oxide by macrophages. PPG may contribute to the binding of Leishmania to host cells and may play a role in modulating the biology of the infected macrophage at the early stage of infection.
Insights
Proteophosphoglycan (PPG), a Leishmania glycoprotein, binds to and is internalized by macrophages. This interaction modulates macrophage responses, potentially aiding parasite entry and early infection.
Area of Science:
- Parasitology
- Immunology
- Molecular Biology
Background:
- Proteophosphoglycan (PPG) is a mucin-like glycoprotein on Leishmania major promastigotes.
- PPG is secreted into culture supernatant and found on amastigotes and in vesicles within infected macrophages.
- Its carbohydrate structure resembles lipophosphoglycan, a known macrophage receptor.
Purpose of the Study:
- To investigate the presence and function of PPG in Leishmania species.
- To determine if PPG binds to macrophages and how it affects macrophage biology.
- To explore PPG's role in the early stages of Leishmania infection.
Main Methods:
- Immunological detection of PPG across Leishmania species.
- Macrophage binding assays for PPG.
- Measurement of macrophage cytokine production (TNF-alpha) and nitric oxide (NO) in response to PPG.
- Co-stimulation experiments with interferon-gamma.
Main Results:
- Antigenically similar PPGs were found in multiple Leishmania species.
- PPG demonstrated time-dependent binding and internalization by macrophages.
- PPG inhibited tumor necrosis factor-alpha production.
- PPG synergized with interferon-gamma to enhance nitric oxide production.
Conclusions:
- PPG is conserved across Leishmania species and interacts with macrophages.
- PPG may facilitate Leishmania binding to host cells.
- PPG plays a role in modulating macrophage biology during early infection, influencing host immune responses.