The production of fully functional human red cells in vitro from haematopoietic stem cells (hHSCs) has been successfully achieved. Recently, the use of hHSCs from cord blood represented a major improvement to develop the continuous culture system for Plasmodium vivax. Here, we demonstrated that CD34+hHSCs from peripheral blood and bone marrow can be expanded and differentiated to reticulocytes using a novel stromal cell. Moreover, these reticulocytes and mature red blood cells express surface markers for entrance of malaria parasites contain adult haemoglobin and are also permissive to invasion by P. vivax and Plasmodium falciparum parasites.

The spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (PRRs) in splenic effector cells during malaria infection is poorly understood. In the present study, we analysed the expression of selected PRRs in splenic effector cells from BALB/c mice infected with the lethal and non-lethal Plasmodium yoelii strains 17XL and 17X, respectively, and the non-lethal Plasmodium chabaudi chabaudi AS strain. The results of these experiments showed fewer significant changes in the expression of PRRs in AS-infected mice than in 17X and 17XL-infected mice. Mannose receptor C type 2 (MRC2) expression increased with parasitemia, whereas Toll-like receptors and sialoadhesin (Sn) decreased in mice infected with P. chabaudi AS. In contrast, MRC type 1 (MRC1), MRC2 and EGF-like module containing mucin-like hormone receptor-like sequence 1 (F4/80) expression decreased with parasitemia in mice infected with 17X, whereas MRC1 an MRC2 increased and F4/80 decreased in mice infected with 17XL. Furthermore, macrophage receptor with collagenous structure and CD68 declined rapidly after initial parasitemia. SIGNR1 and Sn expression demonstrated minor variations in the spleens of mice infected with either strain. Notably, macrophage scavenger receptor (Msr1) and dendritic cell-associated C-type lectin 2 expression increased at both the transcript and protein levels in 17XL-infected mice with 50% parasitemia. Furthermore, the increased lethality of 17X infection in Msr1 -/- mice demonstrated a protective role for Msr1. Our results suggest a dual role for these receptors in parasite clearance and protection in 17X infection and lethality in 17XL infection.

O ciclo eritrocítico do Plasmodium falciparum apresenta uma particularidade em relação às outras espécies de Plasmodium que infectam o homem. Trofozoítas maduros e esquizontes são seqüestrados da circulação periférica devido à adesão de eritrócitos infectados às células endoteliais. Modificações na superfície dos eritrócitos infectados, denominadas "knobs", permitem adesão ao endotélio e a outros eritrócitos. A adesão fornece uma melhor maturação na atmosfera venosa microaerofílica e permite que o parasita escape do clareamento pelo baço, que reconhece a perda de deformabilidade do eritrócito infectado. A adesão ao endotélio ou citoaderência, tem importante função na patogenicidade da doença, causando obstrução de pequenos vasos e contribuindo para danos em muitos órgãos. Citoaderência designa também a adesão de eritrócitos infectados a eritrócitos não infectados, fenômeno amplamente conhecido como "rosetting". Aspectos clínicos da malária grave bem como receptores do hospedeiro e ligantes do parasita envolvidos em citoaderência e "rosetting", são revisados aqui. A proteína de membrana do eritrócito 1 de P. falciparum (PfEMP1) parece ser o principal ligante adesivo dos eritrócitos infectados e será discutida em maiores detalhes. Uma melhor compreensão da função dos receptores do hospedeiro e dos ligantes do parasita no desenvolvimento de diferentes síndromes clínicas é urgentemente necessária para identificar alvos para vacinação visando diminuir as taxas de mortalidade desta doença.

The erythrocytic cycle of Plasmodium falciparum presents a particularity in relation to other Plasmodium species that infect man. Mature trophozoites and schizonts are sequestered from the peripheral circulation due to adhesion of infected erythrocytes to host endothelial cells. Modifications in the surface of infected erythrocytes, termed knobs, seem to facilitate adhesion to endothelium and other erythrocytes. Adhesion provides better maturation in the microaerophilic venous atmosphere and allows the parasite to escape clearance by the spleen which recognizes the erythrocytes loss of deformability. Adhesion to the endothelium, or cytoadherence, has an important role in the pathogenicity of the disease, causing occlusion of small vessels and contributing to failure of many organs. Cytoadherence can also describe adhesion of infected erythrocytes to uninfected erythrocytes, a phenomenon widely known as rosetting. Clinical aspects of severe malaria, as well as the host receptors and parasite ligands involved in cytoadherence and rosetting, are reviewed here. The erythrocyte membrane protein 1 of P. falciparum (PfEMP1) appears to be the principal adhesive ligand of infected erythrocytes and will be discussed in more detail. Understanding the role of host receptors and parasite ligands in the development of different clinical syndromes is urgently needed to identify vaccination targets in order to decrease the mortality rates of this disease.