The resistance of intracellular Leishmania parasites to digestion by lysosomal enzymes.

Infections of Leishmania mexicana in cultured normal mouse peritoneal macrophages show different morphological features depending on whether the parasites invade as promastigote or amastigote forms. Infections derived from promastigote invasion are characterized by parasitophorous vacuoles which develop slowly, and acquire only modest proportions. In contrast, the organisms in amastigote-derived infections lie within parasitophorous vacuoles which develop more rapidly, and attain a much greater size. From observation of promastigotes of different species of Leishmania, it appeared that survival subsequent to endocytosis by normal macrophages depends on the parasites' rapid transformation to the amastigote form. Activation of the macrophage population produced an enhanced parasiticidal effect only against incompletely transformed Leishmania promastigotes. Electron microscope investigations, involving enzyme histochemistry and lysosome labelling techniques, indicate that intracellular Leishmania avoid digestion by interfering with the activity of lysosomal enzymes that are freely delivered to the parasitophorous vacuole. It is proposed that this ability is acquired on transformation to the amastigote, and incidentally induces fluid distension of the parasitophorous vacuole through phenomena recently described by other workers.