Mannose receptor (MR) and Toll-like receptor 2 (TLR2) influence phagosome maturation during Leishmania infection.

Abstract

Leishmania enter macrophages through receptor-mediated phagocytosis and survive the harsh environment of a phagolysosome. Here, we investigated the interaction between mannose receptor (MR), Toll-like receptor 2 (TLR2), and Leishmania, and the subsequent impact on phagosome maturation. Leishmania parasites are able to delay phagosome maturation, not reaching full maturation until 5hours post-engulfment. Here, maturation of Leishmania major- and Leishmania donovani-containing phagosomes proceeded as expected in the WT macrophages becoming LAMP1 positive by 6hours. Interestingly, MR-/- macrophages become LAMP1 positive by ~2hours and ~4hours post-infection Leishmania-containing phagosomes lost LAMP1 expression and gained the early marker EEA1. LAMP1 expression was again observed by 6hours. Leishmania LPG was essential for the delay in both WT and MR-/- macrophages but was not essential for the early maturation (2hours) observed in MR-/- macrophages. Serum opsonization of Leishmania prior to infection induced identical phagosome maturation patterns in WT and MR-/- macrophages. In the absence of MyD88 or TLR2 on macrophages, Leishmania phagosomes matured significantly faster, becoming LAMP1 positive by ~1-2hours. These studies add to the knowledge that phagosome maturation is influenced by multiple receptor-ligand interactions and signalling pathways.