Plasmodium Falciparum: New Vector with Bi-directional Promoter Activity to Stably Express Transgenes

Experimental Parasitology. Jan-Feb, 2003  |  Pubmed ID: 12810052

Pilot Survey of Expressed Sequence Tags (ESTs) from the Asexual Blood Stages of Plasmodium Vivax in Human Patients

Malaria Journal. Jul, 2003  |  Pubmed ID: 12914668

Plasmodium vivax is the most widely distributed human malaria, responsible for 70-80 million clinical cases each year and large socio-economical burdens for countries such as Brazil where it is the most prevalent species. Unfortunately, due to the impossibility of growing this parasite in continuous in vitro culture, research on P. vivax remains largely neglected.

Malaria Parasites Lacking Eef1a Have a Normal S/M Phase Yet Grow More Slowly Due to a Longer G1 Phase

Molecular Microbiology. Dec, 2003  |  Pubmed ID: 14651637

Eukaryotic elongation factor 1A (eEF1A) plays a central role in protein synthesis, cell growth and morphology. Malaria parasites possess two identical genes encoding eEF1A (eef1aa and eef1ab). Using pbeef1a-Plasmodium berghei mutants that lack an eEF1a gene, we demonstrate that the level of eEF1A production affects the proliferation of blood stages and parasite fitness. Pbeef1a- parasites can complete the vertebrate and mosquito phases of the life cycle, but the growth phase of the asexual blood stages is extended by up to 20%. Analysis of the cell cycle by flow cytometry as well as transcriptional analyses revealed that the duration of the S and M phases and the number of daughter cells produced were not detectably affected, but that the G1 phase is elongated. Thus, as in budding yeast, a growth threshold must be achieved by blood-stage Plasmodium parasites to permit transition from G1 into S/M phase. Initial analyses indicate that transcriptional events associated with gametocyte development were not remarkably retarded. Insight into protein synthesis and its influence on cell proliferation might be used to generate slow-growing (attenuated) parasites.

The Methylerythritol Phosphate Pathway is Functionally Active in All Intraerythrocytic Stages of Plasmodium Falciparum

The Journal of Biological Chemistry. Dec, 2004  |  Pubmed ID: 15452112

Two genes encoding the enzymes 1-deoxy-D-xylulose-5-phosphate synthase and 1-deoxy-D-xylulose-5-phosphate reductoisomerase have been recently identified, suggesting that isoprenoid biosynthesis in Plasmodium falciparum depends on the methylerythritol phosphate (MEP) pathway, and that fosmidomycin could inhibit the activity of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. The metabolite 1-deoxy-D-xylulose-5-phosphate is not only an intermediate of the MEP pathway for the biosynthesis of isopentenyl diphosphate but is also involved in the biosynthesis of thiamin (vitamin B1) and pyridoxal (vitamin B6) in plants and many microorganisms. Herein we report the first isolation and characterization of most downstream intermediates of the MEP pathway in the three intraerythrocytic stages of P. falciparum. These include, 1-deoxy-D-xylulose-5-phosphate, 2-C-methyl-D-erythritol-4-phosphate, 4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol, 4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol-2-phosphate, and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. These intermediates were purified by HPLC and structurally characterized via biochemical and electrospray mass spectrometric analyses. We have also investigated the effect of fosmidomycin on the biosynthesis of each intermediate of this pathway and isoprenoid biosynthesis (dolichols and ubiquinones). For the first time, therefore, it is demonstrated that the MEP pathway is functionally active in all intraerythrocytic forms of P. falciparum, and de novo biosynthesis of pyridoxal in a protozoan is reported. Its absence in the human host makes both pathways very attractive as potential new targets for antimalarial drug development.

Variant Genes and the Spleen in Plasmodium Vivax Malaria

International Journal for Parasitology. Dec, 2004  |  Pubmed ID: 15582531

It is generally accepted that Plasmodium vivax, the most widely distributed human malaria, does not cytoadhere in the deep capillaries of inner organs and thus this malaria parasite must have evolved splenic evasion mechanism in addition to sequestration. The spleen is a uniquely adapted lymphoid organ whose central function is the selective clearance of cell and other particles from the blood, and microbes including malaria. Splenomegaly is a hallmark of malaria and no other disease seems to exacerbate this organ as this disease does. Besides this major selective clearance function however, the spleen is also an erythropoietic organ which, under stress conditions, can be responsible for close to 40% of the RBC populations. Data obtained in experimental infections of human patients with P. vivax showed that anaemia is associated with acute and chronic infections and it has been postulated that the continued parasitemia might have been sufficient to infect and destroy most circulating reticulocytes. We review here the basis of our current knowledge of variant genes in P. vivax and the structure and function of the spleen during malaria. Based on this data, we propose that P. vivax specifically adhere to barrier cells in the human spleen allowing the parasite to escape spleen-clearance while favouring the release of merozoites in an environment where reticulocytes, the predominant, if not exclusive, host cell of P. vivax, are stored before their release into circulation to compensate for the anaemia associated with vivax malaria.

Plasmodium Vivax: Allele Variants of the Mdr1 Gene Do Not Associate with Chloroquine Resistance Among Isolates from Brazil, Papua, and Monkey-adapted Strains

Experimental Parasitology. Apr, 2005  |  Pubmed ID: 15755424

We describe here the sequence of the Plasmodium vivax mdr1 gene from 10 different isolates differing in chloroquine sensitivity. The deduced amino acid sequence of PvMDR1 shares more than 70% similarity with other malarial MDR proteins and it displays consensus motifs of an ABC family transporter including two transmembrane domains and two ATP binding cassettes. Similarity and dendrogram analyses revealed that sequences could be grouped according to their geographical origin. Within each geographical group however, no correlation was found between chloroquine resistance and specific mutations.

Mining the Malaria Transcriptome

Trends in Parasitology. Aug, 2005  |  Pubmed ID: 15979411

Malaria remains the most devastating parasitic disease worldwide, and is responsible each year for >500 million infections and between one million and two million deaths of children under five years of age. Plasmodium falciparum is the most prevalent and deadly malaria parasite of humans, and a huge amount of data about it is now publicly available following completion of its genome sequence, the complete transcriptome of its asexual blood stages and proteomic analyses of its different life stages. Thus, new computational approaches are needed to analyze these data to yield biologically meaningful results that can be validated experimentally and, hopefully, lead to alternative control strategies. In this article, we highlight the importance of new computational approaches in mining the malaria transcriptome of the intraerythrocytic developmental cycle of P. falciparum.

Clinical and Molecular Aspects of Severe Malaria

Anais Da Academia Brasileira De Ciências. Sep, 2005  |  Pubmed ID: 16127552

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.

Variant Proteins of Plasmodium Vivax Are Not Clonally Expressed in Natural Infections

Molecular Microbiology. Nov, 2005  |  Pubmed ID: 16238616

Plasmodium vivax is the most widely distributed human malaria parasite and responsible for 70-80 million clinical cases each year and a large socio-economical burden. The sequence of a chromosome end from P. vivax revealed the existence of a multigene superfamily, termed vir (P. vivax variant antigens), that can be subdivided into different subfamilies based on sequence similarity analysis and which represents close to 10-20% of the coding sequences of the parasite. Here we show that there is a vast repertoire of vir genes abundantly expressed in isolates obtained from human patients, that different vir gene subfamilies are transcribed in mature asexual blood stages by individual parasites, that VIR proteins are not clonally expressed and that there is no significant difference in the recognition of VIR-tags by immune sera of first-infected patients compared with sera of multiple-infected patients. These data provide to our knowledge the first comprehensive study of vir genes and their encoding variant proteins in natural infections and thus constitute a baseline for future studies of this multigene superfamily. Moreover, whereas our data are consistent with a major role of vir genes in natural infections, they are inconsistent with a predominant role in the strict sense of antigenic variation.

A Reduced Risk of Infection with Plasmodium Vivax and Clinical Protection Against Malaria Are Associated with Antibodies Against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

Infection and Immunity. May, 2006  |  Pubmed ID: 16622209

Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite.

Origins of Sequence Diversity in the Malaria Vaccine Candidate Merozoite Surface Protein-2 (MSP-2) in Amazonian Isolates of Plasmodium Falciparum

Gene. Jul, 2006  |  Pubmed ID: 16716539

The recent evolution of Plasmodium falciparum is at odds with the extensive polymorphism found in most genes coding for antigens. Here, we examined the patterns and putative mechanisms of sequence diversification in the merozoite surface protein-2 (MSP-2), a major malarial repetitive surface antigen. We compared the msp-2 gene sequences from closely related clones derived from sympatric parasite isolates from Brazilian Amazonia and used microsatellite typing to examine, in these same clones, the haplotype background of chromosome 2, where msp-2 is located. We found examples of msp-2 sequence rearrangements putatively created by nonreciprocal recombinational events, such as replication slippage and gene conversion, while maintaining the chromosome haplotype. We conclude that these nonreciprocal recombination events may represent a major source of antigenic diversity in MSP-2 in P. falciparum populations with low rates of classical meiotic recombination.

Multi-character Population Study of the Vir Subtelomeric Multigene Superfamily of Plasmodium Vivax, a Major Human Malaria Parasite

Molecular and Biochemical Parasitology. Sep, 2006  |  Pubmed ID: 16730808

Plasmodium vivax, the most widely distributed human malaria parasite, contains the subtelomeric multigene vir superfamily corresponding to circa 10% of its coding genome. In this work, we used a multi-character strategy to study the vir gene repertoire circulating in natural parasite populations obtained directly from 32 human patients from endemic regions of Brazil and Sri Lanka. Cladistic analysis confirmed the existence of vir subfamilies, which varied in size and allele polymorphisms. Moreover, different motifs, protein domain, and secondary structures were predicted for each subfamily. Of importance, not all vir sequences possess a recognizable Pexel motif recently shown to be important, though not essential, signal for transportation to the cell membrane of infected red blood cells. Furthermore, subfamilies A and D display common structural features with the recently described P. falciparum SURFIN and Pfmc-2tm subtelomeric multigene families. These results suggest that VIR proteins can have different subcellular localizations and functions. This is the first study on a population level of the P. vivax vir subtelomeric multigene superfamily.

Extense Variant Gene Family Repertoire Overlap in Western Amazon Plasmodium Falciparum Isolates

Molecular and Biochemical Parasitology. Dec, 2006  |  Pubmed ID: 16938359

In order to find a molecular basis for observations of relatively fast developing immunity to malarial infections in the Western Amazon region, the partial var, stevor and rif gene repertoires of nine different Plasmodium falciparum isolates collected in 1985 and 2000-2004 were evaluated. In contrast to previous results from South East Asia, the variant gene repertoire in Brazilian isolates is rather small and redundant. While the individual var repertoire sizes of Brazilian strains did not differ from Southeast Asian/African isolates, we found an over three times higher overlap of var sequence repertoires in Amazonian strains which was also conserved over time, suggesting the ongoing circulation of a similar var gene repertoire. Coincidently, almost 40% of the sequences identified herein showed the highest degree of similarity to var genes from either Brazilian or Venezuelan isolates, indicating a limited var repertoire of P. falciparum in the Amazon Basin as a whole. The intrastrain similarities of var genes were slightly but significantly lower than in Southeast Asian/African samples suggesting a higher selective pressure for diversification in Amazonian isolates. Despite of higher copy numbers per genome, rif genes also showed a significant repertoire overlap. stevor genes, which share the same predominant subtelomeric localization as var and rif genes, showed a still higher repertoire overlap and were highly similar to 3D7 stevor genes, indicating stronger functional conservation than var and rif genes. This is the first study that reveals that P. falciparum variant gene repertoires of certain areas can be limited. This has important implications for the strain-specific immunity against variant antigens occurring in these areas.

Expression and Function of Pvcrt-o, a Plasmodium Vivax Ortholog of Pfcrt, in Plasmodium Falciparum and Dictyostelium Discoideum

Molecular and Biochemical Parasitology. Dec, 2006  |  Pubmed ID: 16987557

Chloroquine resistance in Plasmodium vivax threatens the use of this drug as first-line treatment for millions of people infected each year worldwide. Unlike Plasmodium falciparum, in which chloroquine resistance is associated with mutations in the pfcrt gene encoding a digestive vacuole transmembrane protein, no point mutations have been associated with chloroquine resistance in the P. vivax ortholog gene, pvcrt-o (also called pvcg10). However, the question remains whether pvcrt-o can affect chloroquine response independent of mutations. Since P. vivax cannot be cultured in vitro, we used two heterologous expression systems to address this question. Results from the first system, in which chloroquine sensitive P. falciparum parasites were transformed with pvcrt-o, showed a 2.2-fold increase in chloroquine tolerance with pvcrt-o expression under a strong promoter; this effect was reversed by verapamil. In the second system, wild type pvcrt-o or a mutated form of the gene was expressed in Dictyostelium discoideum. Forms of PvCRT-o engineered to express either lysine or threonine at position 76 produced a verapamil-reversible reduction of chloroquine accumulation in this system to approximately 60% of that in control cells. Our data support an effect of PvCRT-o on chloroquine transport and/or accumulation by P. vivax, independent of the K76T amino acid substitution.

Evaluation of the Acquired Immune Responses to Plasmodium Vivax VIR Variant Antigens in Individuals Living in Malaria-endemic Areas of Brazil

Malaria Journal. 2006  |  Pubmed ID: 17026752

The naturally-acquired immune response to Plasmodium vivax variant antigens (VIR) was evaluated in individuals exposed to malaria and living in different endemic areas for malaria in the north of Brazil.

Promoter Regions of Plasmodium Vivax Are Poorly or Not Recognized by Plasmodium Falciparum

Malaria Journal. 2007  |  Pubmed ID: 17313673

Heterologous promoter analysis in Plasmodium has revealed the existence of conserved cis regulatory elements as promoters from different species can drive expression of reporter genes in heterologous transfection assays. Here, the functional characterization of different Plasmodium vivax promoters in Plasmodium falciparum using luciferase as the reporter gene is presented.

Computational Methods in Noncoding RNA Research

Journal of Mathematical Biology. Jan, 2008  |  Pubmed ID: 17786447

Non protein-coding RNAs (ncRNAs) are a research hotspot in bioinformatics. Recent discoveries have revealed new ncRNA families performing a variety of roles, from gene expression regulation to catalytic activities. It is also believed that other families are still to be unveiled. Computational methods developed for protein coding genes often fail when searching for ncRNAs. Noncoding RNAs functionality is often heavily dependent on their secondary structure, which makes gene discovery very different from protein coding RNA genes. This motivated the development of specific methods for ncRNA research. This article reviews the main approaches used to identify ncRNAs and predict secondary structure.

Comparative Genomics of the Neglected Human Malaria Parasite Plasmodium Vivax

Nature. Oct, 2008  |  Pubmed ID: 18843361

The human malaria parasite Plasmodium vivax is responsible for 25-40% of the approximately 515 million annual cases of malaria worldwide. Although seldom fatal, the parasite elicits severe and incapacitating clinical symptoms and often causes relapses months after a primary infection has cleared. Despite its importance as a major human pathogen, P. vivax is little studied because it cannot be propagated continuously in the laboratory except in non-human primates. We sequenced the genome of P. vivax to shed light on its distinctive biological features, and as a means to drive development of new drugs and vaccines. Here we describe the synteny and isochore structure of P. vivax chromosomes, and show that the parasite resembles other malaria parasites in gene content and metabolic potential, but possesses novel gene families and potential alternative invasion pathways not recognized previously. Completion of the P. vivax genome provides the scientific community with a valuable resource that can be used to advance investigation into this neglected species.

Plasmodium Vivax and the Importance of the Subtelomeric Multigene Vir Superfamily

Trends in Parasitology. Jan, 2009  |  Pubmed ID: 19036639

Plasmodium vivax is responsible for more than 100 million clinical cases yearly. Unlike P. falciparum, in which infected red blood cells cytoadhere via variant proteins, avoiding passage through the spleen, P.-vivax-infected reticulocytes seem not to cytoadhere. However, a variant subtelomeric multigene vir family has been identified in P. vivax. Thus, questions remain about how P. vivax circulates through the spleen and the role of Vir proteins. In this review, the importance of the vir multigene superfamily is reviewed in the light of the completion of the entire genome sequence of P. vivax and from data gathered from experimental infections in reticulocyte-prone non-lethal malaria parasites and natural P. vivax infections.

Increased Expression Levels of the Pvcrt-o and Pvmdr1 Genes in a Patient with Severe Plasmodium Vivax Malaria

Malaria Journal. 2009  |  Pubmed ID: 19341456

There are increasing reports of severe clinical cases exclusively associated with Plasmodium vivax infections. Notably, this severity has been recently suggested to be associated with chloroquine resistance.

Analysis of Single-nucleotide Polymorphisms in the Crt-o and Mdr1 Genes of Plasmodium Vivax Among Chloroquine-resistant Isolates from the Brazilian Amazon Region

Antimicrobial Agents and Chemotherapy. Aug, 2009  |  Pubmed ID: 19451296

Plasmodium vivax parasites with chloroquine resistance (CQR) are already circulating in the Brazilian Amazon. Complete single-nucleotide polymorphism (SNP) analyses of coding and noncoding sequences of the pvmdr1 and pvcrt-o genes revealed no associations with CQR, even if some mutations had not been randomly selected. In addition, striking differences in the topologies and numbers of SNPs in these transporter genes between P. vivax and P. falciparum reinforce the idea that mechanisms other than mutations may explain this virulent phenotype in P. vivax.

Key Gaps in the Knowledge of Plasmodium Vivax, a Neglected Human Malaria Parasite

The Lancet Infectious Diseases. Sep, 2009  |  Pubmed ID: 19695492

Plasmodium vivax is geographically the most widely distributed cause of malaria in people, with up to 2.5 billion people at risk and an estimated 80 million to 300 million clinical cases every year--including severe disease and death. Despite this large burden of disease, P vivax is overlooked and left in the shadow of the enormous problem caused by Plasmodium falciparum in sub-Saharan Africa. The technological advances enabling the sequencing of the P vivax genome and a recent call for worldwide malaria eradication have together placed new emphasis on the importance of addressing P vivax as a major public health problem. However, because of this parasite's biology, it is especially difficult to interrupt the transmission of P vivax, and experts agree that the available methods for preventing and treating infections with P vivax are inadequate. It is thus imperative that the development of new methods and strategies become a priority. Advancing the development of such methods needs renewed emphasis on understanding the biology, pathogenesis, and epidemiology of P vivax. This Review critically examines what is known about P vivax, focusing on identifying the crucial gaps that create obstacles to the elimination of this parasite in human populations.

Naturally-acquired Humoral Immune Responses Against the N- and C-termini of the Plasmodium Vivax MSP1 Protein in Endemic Regions of Brazil and Papua New Guinea Using a Multiplex Assay

Malaria Journal. 2010  |  Pubmed ID: 20092651

Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic.

On the Cytoadhesion of Plasmodium Vivax-infected Erythrocytes

The Journal of Infectious Diseases. Aug, 2010  |  Pubmed ID: 20617923

Plasmodium falciparum and Plasmodium vivax are responsible for most of the global burden of malaria. Although the accentuated pathogenicity of P. falciparum occurs because of sequestration of the mature erythrocytic forms in the microvasculature, this phenomenon has not yet been noted in P. vivax. The increasing number of severe manifestations of P. vivax infections, similar to those observed for severe falciparum malaria, suggests that key pathogenic mechanisms (eg, cytoadherence) might be shared by the 2 parasites.

Comparison of Diagnostic Methods for the Detection and Quantification of the Four Sympatric Plasmodium Species in Field Samples from Papua New Guinea

Malaria Journal. 2010  |  Pubmed ID: 21156052

Accurate diagnosis of Plasmodium infections is essential for malaria morbidity and mortality reduction in tropical areas. Despite great advantages of light microscopy (LM) for malaria diagnosis, its limited sensitivity is a critical shortfall for epidemiological studies. Robust molecular diagnostics tools are thus needed.

Plasmodium Vivax: Comparison of Immunogenicity Among Proteins Expressed in the Cell-free Systems of Escherichia Coli and Wheat Germ by Suspension Array Assays

Malaria Journal. 2011  |  Pubmed ID: 21756349

In vitro cell-free systems for protein expression with extracts from prokaryotic (Escherichia coli) or eukaryotic (wheat germ) cells coupled to solid matrices have offered a valid approach for antigen discovery in malaria research. However, no comparative analysis of both systems is presently available nor the usage of suspension array technologies, which offer nearly solution phase kinetics.

Exosomes from Plasmodium Yoelii-infected Reticulocytes Protect Mice from Lethal Infections

PloS One. 2011  |  Pubmed ID: 22046311

Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released after the fusion of multivesicular bodies (MVBs) with the plasma membrane. While initial studies suggested that the role of exosomes was limited to the removal of proteins during the maturation of reticulocytes to erythrocytes, recent studies indicate that they are produced by different types of cells and are involved in promoting inter-cellular communication and antigen presentation. Here, we describe the isolation and characterization of exosomes from peripheral blood of BALB/c mice infected with the reticulocyte-prone non-lethal Plasmodium yoelii 17X strain. Importantly, proteomic analysis revealed the presence of parasite proteins in these vesicles. Moreover, immunization of mice with purified exosomes elicited IgG antibodies capable of recognizing P. yoelii-infected red blood cells. Furthermore, lethal challenge of immunized mice with the normocyte-prone lethal P. yoelii 17XL strain caused a significant attenuation in the course of parasitaemia, increased survival time, and altered the cell tropism to reticulocytes. These results were obtained also when the exosomes were isolated from a P. yoelii-infected reticulocyte culture indicating that reticulocyte-derived exosomes carry antigens and are involved in immune modulation. Moreover, inclusion of CpG ODN 1826 in exosome immunizations elicited IgG2a and IgG2b antibodies and promoted survival, clearance of parasites and subsequent sterile protection of 83% of the animals challenged with P. yoelli 17XL. To our knowledge, this is the first report of immune responses elicited by exosomes derived from reticulocytes opening new avenues for the modulation of anti-malaria responses.

The Role of the Spleen in Malaria

Cellular Microbiology. Dec, 2011  |  Pubmed ID: 22188297

The spleen is a complex organ that is perfectly adapted to selectively filtering and destroying senescent red blood cells (RBCs), infectious microorganisms and Plasmodium-parasitized RBCs. Infection by malaria is the most common cause of spleen rupture and splenomegaly, albeit variably, a landmark of malaria infection. Here, the role of the spleen in malaria is reviewed with special emphasis in lessons learned from human infections and mouse models.

Strain-specific Spleen Remodelling in Plasmodium Yoelii Infections in Balb/c Mice Facilitates Adherence and Spleen Macrophage-clearance Escape

Cellular Microbiology. Jan, 2011  |  Pubmed ID: 20923452

Knowledge of the dynamic features of the processes driven by malaria parasites in the spleen is lacking. To gain insight into the function and structure of the spleen in malaria, we have implemented intravital microscopy and magnetic resonance imaging of the mouse spleen in experimental infections with non-lethal (17X) and lethal (17XL) Plasmodium yoelii strains. Noticeably, there was higher parasite accumulation, reduced motility, loss of directionality, increased residence time and altered magnetic resonance only in the spleens of mice infected with 17X. Moreover, these differences were associated with the formation of a strain-specific induced spleen tissue barrier of fibroblastic origin, with red pulp macrophage-clearance evasion and with adherence of infected red blood cells to this barrier. Our data suggest that in this reticulocyte-prone non-lethal rodent malaria model, passage through the spleen is different from what is known in other Plasmodium species and open new avenues for functional/structural studies of this lymphoid organ in malaria.