The role of spleen macrophages in malaria: an ultrastructural study

Abstract

A n electronmicroscopy study o f the spleen fro m mice infected withThe predominantly intraerythrocytic habitat of malarial parasites and the fact that gross changes in the splenic microarchitecture occur during m alaria8 , make the spleen an im portant organ in which to study host -parasite interactions. A t this site parasites are removed from the blood, phagocytosed, and both induce and are subjected to the effects of the immune response. Although macrophages play a central role in ali these events, our understanding of their functions is still very fragmentary and several important questions remain unanswered. This study was therefore undertaken to investigate the nature of phagocytic cells from different areas of the spleen during malaria infection, and the mechanisms by which they remove parasites from the blood. strain) -infected erythrocytes, and eight days later, anesthetized by ether 30 minutes after an injection of 150 units of heparin intravenously. A polythene cannula (0.61 mm externai diameter) was inserted caudally into the thoracic aorta and its tip secured at the levei of emergence of the coeliac artery. After clamping the distai aorta and sectioning the portal vein, animais were perfused with phosphate buffered saline at 37°C at a pressure of 163 cm of water. After bleaching of the liver, perfusion was switched to the fixation solution of 1.5% glutaraldehyde in 0.1M sodium cacodylate bufferpH 7.3. Spleens were remov ed after 15 min perfusion with the fixative, sliced into sections of 1 mm submitted to a further 2 hour fixation with 4% buffered glutaraldehyde and washed with cacodylate buffer containing 10% sucrose. Tissues were post fixed in veronal-acetate buffered 1 % osmium tetroxide, dehydrated in ethanol, embedded in Araldite and stained with uranyl acetate and lead citrate, and examined by electron microscopy.A reas comprising each major cell compartment of the spleen (red pulp, marginal zone, periarteriolar lymphocyte sheath and germinal centre) were selected in toluidine blue-stained sections, and relocated on the surface of the corresponding block. Phagocytic cells were characterized by the presence of ingested parasites or malarial pigment. The latter was recognized as osmiophilic trapezoidal crystals, sometimes partially dissolved by the lead citrate used for processing the tissue. 31

Macrophage‐fibroblast circuits in the spleen

“…Early microscopy studies in monkeys and mice have established that RPM phagocytose free or internalized parasites and infected erythrocytes. 55,56 In mice, RPM also take part in the control of parasitemia by promoting immune responses during blood stage malaria. Infection of Ifnb-Yfp reporter mice with the rodent malaria parasite P chabaudi has demonstrated that RPM are a primary source of type I interferon, which promotes the inflammatory response needed to fight this parasite.…”

“…Aside from their role in iron homeostasis, RPM are also strategically located to detect and defend the organism against blood‐borne infections, such as malaria. Early microscopy studies in monkeys and mice have established that RPM phagocytose free or internalized parasites and infected erythrocytes 55,56 . In mice, RPM also take part in the control of parasitemia by promoting immune responses during blood stage malaria.…”