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Malaria and macrophages117drugs and insecticides, respectively, have worsened Macrophage (MØ; a cell 13–15 µm in diameter) wasthe malaria problem (Greenwood and Mutabingwa, for the first time identified and described by the father2002). No suitable human anti-malaria vaccine is yet of cell-mediated immunity, a Russian pathologist, Ilyaavailable (Richie and Saul, 2002; Moorthy et al., Ilich Metchinkoff (French adoption; Elie2004), mainly due to the lack of a clear understanding Metchnikoff) in 1893. Though the phagocytosis hasof the molecular mechanism(s) of pathogenesis and been described much earlier in 1862 by Haeckel (citedimmune protection (Miller et al., 2002). It is thought by Nelson, 1969), the concept of phagocytic functionsthat the availability of the complete genome sequence of MØs and its bearing on the host resistance toof P. falciparum (Gardner et al., 2002) and the rapid invasion by parasites was adequately andadvances made in the gene transfer and disruption experimentally documented and forcefully expressedtechniques, may help in understanding several by Metchnikoff (1893; 1905).biological complexities associated with malariaparasite.The role(s) of MØs in malaria has been implicated byGolgi nearly a century ago, when he observed theDuring the bite of a Plasmodium-infected female presence of malaria pigment-leaden splenic MØs inAnopheles mosquito, sporozoites, the infective stage malaria patients. Incidentally, this apparently smallof malaria parasite, are injected into human blood observation later laid the foundation of the notion thatcirculation. Just within nearly 1 h of their injection, phagocytosis of infected-erythrocytes (IE) constitutessporozoites enter liver and invade hepatocytes, where an important, critical step in host defense duringthey undergo schizogony and produce thousands of malaria (Taliaferro and Mulligan, 1937). And now, it ismerozoites (Mz). Due to some yet unknown process, a well established, through both animal model studiesdormant liver stage of malaria parasite, hypnozoite, is and, indirectly, from several clinical observations thatformed, which is responsible for relapses in infections MØ phagocytosis of IE constitutes an important innatecaused only by P. vivax and P. ovale. Following the protective mechanism against malaria (Urban andrupture of infected-hepatocytes, the released Mz, Roberts, 2002). Mota et al. (1998) reported thatfollowing a complex chain of events, enter into antibodies induced in mice during acute P. chabaudierythrocytes and within next few hours, convert into chabaudi malaria, bound the surface of IE and thusring stages of the parasite. Rings start feeding on augmented their phagocytosis by MØs. Peritonealhemoglobin of the erythrocytes, and after 15–18 h MØs from P. yoelli nigeriensis vaccinated mice,develop into full grown trophozoites with a clear food which were completely protected following a lethalvacuole. Trophozoites give rise to multinucleate challenge, showed a great increase in their pool-size,schizonts, which after further growth and and in both the intrinsic phagocytic activity and thedevelopment rupture the now fragile erythrocyte number of MØs involved in phagocytosis, in vitromembrane and release up to 16 Mz. Most of the Mz (Kinhikar et al., 2001). Similarly, protection in miceinvade fresh erythrocytes and continue the blood infected with P. berghei (Singh and Singh, 2001) andcycle, whereas only a few of them, through again a not P. yoelli nigeriensis (Kaur et al., 2002), after coyetfully known process, develop into male and female administration with recombinant mouse granulocytegametocyteswithin the erythrocytes and circulate in macrophage colony-stimulating factor (GM-CSF) andblood, and are taken up by mosquitoes during their methionine-ekephalin (M-ENK), and in P. bergheibloodmeal. In the mosquito midgut, gametocytes infected mice co-treated with GM-CSF and M-ENKundergo gametogenesis to produce male and female fragment peptide Tyr-Gly-Gly (Kaur et al., 2004), wasgametes, which following fertilization produce invariably associated with > 1000-fold increaseddiploid zygotes. Zygotes then undergo meiosis and pahgocytic activity of peritoneal MØs. In all these codifferentiationto produce motile ookinetes, which treated mice, selective killing of MØs with silicathen traverse the midgut wall and develop into completely abrogated the protection. In humanoocysts. As a result of sporogony, sporozoites are malaria, phagocytosis of P. falciparum IE (Vernes,produced in oocysts, which after their release in 1980) and free-merozoites (Khusmith et al., 1982) byhaemocoele, migrate to the salivary gland of the monocytes has been reported. Brown and Greenwoodmosquito. It is thought that in the salivary gland, (1985) demonstrated the role of monocytes/sporozoites undergo some kind of a maturation and, macrophages in P. falciparum IE phagocytosis and itsduring the next blood meal of the mosquito, are correlation with recovery from malaria. In severelyinjected into a new host. compromised immunodeficient mice maintaining P.