BIOCHEMICAL MEDICINE AND METABOLIC BIOLOGY 41, 46-55 (1989) Suppression of Macrophage Lysosomal Enzymes after Leishmania donovani Infection PRASANTA CHAKRABORTY AND PIJUSH K. DAS Leishmania Group, Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Calcutta-700 032, India Received July 15, 1988, andin revised form September 19, 1988 Leishmania donovani is an obligate intracellular parasite residing in the pha- golysosome of the host’s mononuclear phagocytes (1). Infection with this parasite begins with the introduction by the sandfly vector of the flagellated promastigote into the blood stream, leading to intracellular parasitism of macrophages. Mac- rophages constitute one of the primary defense mechanisms of the body against microbial invasion and are capable of fulfilling a variety of microbicidal functions such as the production of free oxygen radicals and lysosomal enzymes and the ability to activate host’s immune system. The means used by Leishmania parasites to overcome the formidable array of macrophage’s killing response is one of the still unsolved mysteries of Leishmania biology. Work on other parasites which live in a similar environment has revealed several possible mechanisms. Thus Toxoplasma (2,3) and Tuber&e bacilli (4) appear to be able to prevent fusion of the destructive macrophage lysosomes with the phagocytic vacuole, whereas Mycobacterium lepraemurium achieves immunity through a physical barrier in the form of a thick enveloping capsule (5,6). Trypanosoma crud is able to escape from the original phagosome and live in direct contact with the cytoplasm (7), thus avoiding the essentially vacuole-bound lysosomal enzymes. The most intriguing event is the finding that lysosome-phagosome fusion occurs after leishmanial entry into macrophages, and that Leishmania species not only survive, but continue to multiply in the phagolysosomes (8,9). Leishmania species are thus processed by macrophages as other digestive particles are, but do not suffer the consequences of lysosomal degradation. How they are able to resist the lysosomal degradation is yet to be elucidated. There are several suggestions: (i) leishmanial cell surface may be naturally resistant to enzyme degradation (9), (ii) carbohydrate moieties of surface glycoproteins may protect against proteolytic degradation (lo), and (iii) release of excretory factors as lysosomal enzyme inhibitors (11). Another possibility might be the suppression of host lysosomal enzyme machinery by Leishmania directly or through some inhibitors. The present 46 0885-4505/89 $3.00 Copyright &I 1989 by Academic Press, Inc. AU rights of reproduction in any form reserwd.