Читать книгу Parasitology - Alan Gunn - Страница 106

After an infected sandfly feeds, mononuclear phagocytes quickly detect and ingest the promastigotes that enter the blood circulation. Initial attachment of a parasite to a phagocyte begins at the tip of the parasite’s flagellum via a ligand‐receptor process. The principal ligands are phosphoglycans and the zinc metalloprotease enzyme GP63 (glycoprotein 63) on the surface of the promastigote whilst on the phagocyte, a variety of complement receptors are involved in the attachment process. After phagocytosing the Leishmania parasite, a phagocyte holds it within a membrane‐bound vesicle called a phagosome. Lysomes then fuse with the phagosome and discharge hydrolytic enzymes and microbicidal peptides into it. They also acidify the contents. The structure then becomes to known as a parasitophorous vacuole or phagolysosome. Different species of Leishmania cause the formation of different types of phagolysosomes: those produced by L. mexicana tend to be large and contain many parasites whilst those formed by L. donovani tend to be much smaller.

The combination of a rise in temperature associated with moving to a mammalian host and the drop in pH caused by enclosure within a phagolysosome induce the promastigote to change into the amastigote form. This transformation takes about 1–4 hours following ingestion and is essential if the parasite is to survive the acidic pH and hydrolytic enzymes within the phagolysosome. Transformation includes changes the composition of the cell surface phosphoglycans. Some of these, the glycoinositol phospholipids (GIPLs) directly inhibit the production of nitric oxide (NO) by the phagocyte. The expression of GP63 is downregulated in the amastigote but they continue to express it, and it is important for both the survival of the parasite and as a virulence factor (Olivier et al. 2012). The membrane changes associated with transformation to the amastigote stage means amastigotes invade phagocytes using a different set of ligands and receptors to the promastigote stage. Despite these changes, phagocytes remain capable of destroying amastigotes. Therefore, the reasons why some people develop serious or even fatal infections, whilst in others the infection is resolved, possibly without displaying any symptoms is uncertain.