Plasmodium Berghei Infection Research Articles

VEGF: inflammatory paradoxes

Invited commentary on ‘VEGF and LPS synergistically silence inflammatory response to Plasmodium berghei infection and protect against cerebral malaria’ and ‘Vascular Endothelial Growth factor (VEGF) and Lovastatin suppress the inflammatory response to Plasmodium berghei infection and protect against Experimental Cerebral Malaria’ by Canavese et al.

Molecular characterization of SOCS gene and its expression analysis on Plasmodium berghei infection in Anopheles culicifacies

Anopheles culicifacies mosquitoes are able to transmit both falciparum and vivax malaria in India. More than 65% of malaria cases reported annually spread through this vector. Despite the fact that it poses major vectorial burden in India, the molecular basis of its immune role against Plasmodium development has not been explored intensively. Here, we characterized An. culicifacies SOCS (suppressor of cytokine signaling) gene, a regulator of STAT pathway and its expression analysis upon Plasmodium infection. Our analysis has demonstrated that An. culicifacies SOCS gene shares strikingly high level of sequence similarity in SH2 domain and SOCS box region with other mosquito species. However, its N-terminal identity is limited to Anophelines mosquito only, suggesting its genus specific role. SOCS mRNA is expressed in all developmental stages of mosquito and its expression is higher in male than female adults. SOCS mRNA is significantly induced after Plasmodium infection in midgut tissue indicating its involvement in the immune defense responses. This is the first evidence of involvement of SOCS as an immune gene in Indian malaria vector An. culicifacies.

Gene expression changes in the salivary glands of Anopheles coluzzii elicited by Plasmodium berghei infection.

BackgroundMalaria is a devastating infectious disease caused by Plasmodium parasites transmitted through the bites of infected Anopheles mosquitoes. Salivary glands are the only mosquito tissue invaded by Plasmodium sporozoites, being a key stage for the effective parasite transmission, making the study of Anopheles sialome highly relevant.MethodsRNA-sequencing was used to compare differential gene expression in salivary glands of uninfected and Plasmodium berghei-infected Anopheles coluzzii mosquitoes. RNA-seq results were validated by quantitative RT-PCR. The transmembrane glucose transporter gene AGAP007752 was selected for functional analysis by RNA interference. The effect of gene silencing on infection level was evaluated. The putative function and tertiary structure of the protein was assessed.ResultsRNA-seq data showed that 2588 genes were differentially expressed in mosquitoes salivary glands in response to P. berghei infection, being 1578 upregulated and 1010 downregulated. Metabolism, Immunity, Replication/Transcription/Translation, Proteolysis and Transport were the mosquito gene functional classes more affected by parasite infection. Endopeptidase coding genes were the most abundant within the differentially expressed genes in infected salivary glands (P < 0.001). Based on its putative function and expression level, the transmembrane glucose transporter gene, AGAP007752, was selected for functional analysis by RNA interference. The results demonstrated that the number of sporozoites was 44.3 % lower in mosquitoes fed on infected mice after AGAPP007752 gene knockdown when compared to control (P < 0.01).ConclusionsOur hypothesis is that the protein encoded by the gene AGAPP007752 may play a role on An. coluzzii salivary glands infection by Plasmodium parasite, working as a sporozoite receptor and/or promoting a favorable environment for the capacity of sporozoites.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-1079-8) contains supplementary material, which is available to authorized users.

VEGF and LPS synergistically silence inflammatory response to Plasmodium berghei infection and protect against cerebral malaria

Malaria infection induces, alongside endothelial damage and obstruction hypoxia, a potent inflammatory response similar to that observed in other systemic diseases caused by bacteria and viruses. Accordingly, it is increasingly recognised that cerebral malaria (CM), the most severe and life threatening complication of Plasmodium falciparum infection, bears a number of similarities with sepsis, an often fatal condition associated with a misregulated inflammatory response triggered by systemic microbial infections.Using a Plasmodium berghei ANKA mouse model, histology, immunohistochemistry and gene expression analysis, we showed that lipopolysaccharide S (LPS), at doses that normally induce inflammation tolerance, protects P. berghei infected mice against experimental CM (ECM). Vascular endothelial growth factor (VEGF) preserved blood vessel integrity, and the combination with LPS resulted in a strong synergistic effect. Treated mice did not develop ECM, showed a prolonged survival and failed to develop a significant inflammatory response and splenomegaly in spite of normal parasite loads. The protective role of VEGF was further confirmed by the observation that the treatment of P. berghei infected C57BL/6 and Balb/c mice with the VEGF receptor inhibitor axitinib exacerbates cerebral pathology and aggravates the course of infection. Infected mice treated with VEGF and LPS showed an induction of the anti-inflammatory genes Nrf2 and HO-1 and a suppression to basal levels of the genes IFN-γ and TNF-α. These results provide the rationale for developing new therapeutic approaches against CM and shed new light on how the inflammatory process can be modulated in the presence of systemic infectious diseases.

Vascular endothelial growth factor (VEGF) and lovastatin suppress the inflammatory response to Plasmodium berghei infection and protect against experimental cerebral malaria

Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection, which is associated with high mortality and long-term cognitive impairment even when effective anti-parasitic treatment is administered. Supportive therapy is needed to improve both morbidity and mortality associated with this condition. In an accompanying paper, we have demonstrated that in the Plasmodium berghei ANKA (PbA) rodent model, CM can be effectively prevented by a treatment combining sub-lethal doses of lipopolysaccharide S (LPS) and vascular endothelial growth factor (VEGF). Since LPS is not suitable for human therapy, we investigated whether lovastatin would represent a suitable substitute. This compound, widely used to lower cholesterol levels in plasma, shares with LPS the ability to elicit an anti-inflammatory response by activating the Nrf-2 gene, and when given to P. berghei-infected mice prevents to some extent the onset of CM. We show here that lovastatin- and VEGF-treated mice did not develop CM and showed few signs, if any, of endothelial damage and systemic inflammation. The combination treatment was much more effective than lovastatin and VEGF alone. Immunohistochemistry and gene expression analysis indicated that VEGF and LPS together overturned the two pathogenic mechanisms responsible for the development of CM: endothelial damage and disregulated activation of the inflammatory response. These findings provide the rationale for investigating the therapeutic potential of these compounds in human CM as well as in other inflammatory pathologies that respond poorly to steroid and non-steroid anti-inflammatory therapy.

Anopheles Midgut FREP1 Mediates Plasmodium Invasion

Malaria transmission depends on sexual stage Plasmodium parasites successfully invading Anopheline mosquito midguts following a blood meal. However, the molecular mechanisms of Plasmodium invasion of mosquito midguts have not been fully elucidated. Previously, we showed that genetic polymorphisms in the fibrinogen-related protein 1 (FREP1) gene are significantly associated with Plasmodium falciparum infection in Anopheles gambiae, and FREP1 is important for Plasmodium berghei infection of mosquitoes. Here we identify that the FREP1 protein is secreted from the mosquito midgut epithelium and integrated as tetramers into the peritrophic matrix, a chitinous matrix formed inside the midgut lumen after a blood meal feeding. Moreover, we show that the FREP1 can directly bind Plasmodia sexual stage gametocytes and ookinetes. Notably, ablating FREP1 expression or targeting FREP1 with antibodies significantly decreases P. falciparum infection in mosquito midguts. Our data support that the mosquito-expressed FREP1 mediates mosquito midgut invasion by multiple species of Plasmodium parasites via anchoring ookinetes to the peritrophic matrix and enabling parasites to penetrate the peritrophic matrix and the epithelium. Thus, targeting FREP1 can limit malaria transmission.

Parasite-induced ER stress response in hepatocytes facilitates Plasmodium liver stage infection.

Upon infection of a mammalian host, Plasmodium parasites first replicate inside hepatocytes, generating thousands of new parasites. Although Plasmodium intra-hepatic development represents a substantial metabolic challenge to the host hepatocyte, how infected cells respond to and integrate this stress remains poorly understood. Here, we present proteomic and transcriptomic analyses, revealing that the endoplasmic reticulum (ER)-resident unfolded protein response (UPR) is activated in host hepatocytes upon Plasmodium berghei infection. The expression of XBP1s--the active form of the UPR mediator XBP1--and the liver-specific UPR mediator CREBH is induced by P. berghei infection in vivo. Furthermore, this UPR induction increases parasite liver burden. Altogether, our data suggest that ER stress is a central feature of P. berghei intra-hepatic development, contributing to the success of infection.

Enhancing Efficacy of Antimicrobials with the Medicinal Synthetic Aluminum-Magnesium Silicate, for Prevention and Treatment of Resistant Infections

Aim: To achieve, at least, 95% clearance of loads of treated infections so that pathogens do not develop resistance against drugs used for treatment. Materials and Methodology: Lower doses of Aluminum-magnesium silicate (AMS)-stabilized antimicrobials (Piparazine, Ampicillin, Chloroquine and Sulphadimidine), supported with immune stimulants, were used to treat respective sensitive and resistant infections. Results: Recommended doses of Piparazine, Ampicillin and Chloroquine cleared only 82.94%, 80.68% and 20% of Helignosomoides bakeri, Salmonella gallinarum and Plasmodium berghei infections, respectively. Lower doses (75%) of the AMS-stabilized Piparazine and Ampicillin cleared 96.82% and 97.84% of the treated infections. Supporting the lower doses of AMSstabilized Chloroquine and AMS-stabilized Ampicillin with immune stimulants led to 100% clearance of P. berghei infection and 95.80% clearance of Ampicillin-resistant Escherichia coli infection, respectively. Original Research Article Ezeibe and Ogbonna; BJMMR, 9(6): 1-8, 2015; Article no.BJMMR.17768 2 Conclusion: Prolonging bioavailability of drugs with AMS, minimizing side effects of drugs by using their lower doses for treatment, and enhancing immune responses of treated patients, help treatments to prevent and cure resistant infections.

Anti-hemolysis of Aqueous Crude Extract of Siamese Neem Tree (Azadirachta indica) during Plasmodium berghei Infection in Mice

Malaria-associated hemolysis is associated with mortality in malaria patients. It has been speculated that oxidative stress and inflammation induced by parasite infection and propagation are involved in its pathophysiology. Hence, this study was aimed to investigate the anti-hemolysis of Siamese neem tree (Azadirachta indica) extracts against Plasmodium berghei infection in mice. Leaf aqueous crude extract of Siamese neem tree was prepared using hot water method and used for oral treatment in mice. ICR mice were infected with 1×107 infected red blood cells of P. berghei ANKA by intraperitoneal injection and given the extracts (500, 1,000, and 2,000 mg/kg) for 4-consecutive days. To assess hemolysis, hematocrit levels were then evaluated. Hematocrit level was markedly decreased during malaria parasite propagation in mice. However, anti-hemolytic effect was observed in infected mice treated with the extracts at dose-dependent manners, especially at doses of 1,000 and 2,000 mg/kg. Although hemolysis was observed in pyrimethamine, antimalarial drug, treated group, but it could be protected by combination treatment of pyrimethamine with this extract. In conclusion, aqueous crude extracts of Siamese neem tree exerted anti-hemolysis induced by malaria infection and could be used as combination tre

Effect of Black Tea Extract on Hypoglycemia Induced by Plasmodium berghei ANKA Infection in Mice

Hypoglycemia was found as one of all causes of death in malaria disease and urgently needed to fine new drugs to treat this condition. Hence, the present study was aimed to evaluate the effect of black tea extract on hypoglycemia induced by Plasmodium berghei infection in mice. Aqueous crude extract of black tea was freshly prepared using hot water method and used for efficacy test in vivo. For in vivo test, P. berghei ANKA infected mice were given orally by gavage with 500, 1000, and 2000 mg/kg of black tea extract for 4 consecutive days. Blood glucose levels were then measured. It was found that aqueous crude extract of black tea exerted dose-dependent anti-hypoglycemic activity, especially at a dose of 2000 mg/kg showed the highest activity. Although, pyrimethamine treated group showed significantly (p<0.01) decreasing of blood glucose levels, combination treatment with black tea extract could protect and maintain blood glucose to normal level. It can be concluded that aqueous crude extract of black tea presented anti-hypoglycemic activity against P. berghei infection in mice.

Protective effects of Andrographis paniculata leaf extract on liver and renal damage and hypoglycemia during Plasmodium berghei infection

Liver and renal damage are some causes of deaths in malaria disease. Moreover, hypoglycemia and hypoglycemic shock during malaria infection have also been reported. Therefore, finding new plant extracts to have the activities to protect liver and renal damage as well as hypoglycemia during malaria infection is urgently needed. In this study was aimed to investigate the protective effects of Andrographis paniculata leaf extract on liver and renal damage as well as hypoglycemia induced by Plasmodium berghei ANKA (PbANKA) infection in mice. Aqueous crude extract of A. paniculata leaves was freshly prepared using hot water method. For efficacy test, standard 4-day suppressive test was used. ICR mice were inoculated with 1x107 parasitized erythrocytes of PbANKA by intraperitoneal infected, and given the extract (500, 1000, and 2000 mg/kg) orally by gavage for 4 consecutive days. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, blood urea nitrogen (BUN), creatinine, and glucose were measured. It was found that liver and renal damage were developed during malaria infection as indicated by markedly increasing of AST, ALT, BUN, and creatinine, and decreasing of albumin levels. Additionally, hypoglycemia was also found during the infection. Interestingly, A. paniculata extract showed protective effects on liver and renal damage, and presented anti-hypoglycemia in a dose-dependent manner against infected mice treated with this extract. The highest effect was found at dose of 2000 mg/kg. Moreover, no any side effects were observed in normal mice treated with the extract. It can be concluded that A. paniculata leaf extract can be used as alternative drug to protect liver and renal damage as well as hypoglycemia during malaria infection

Experimental study of the relationship between Plasmodium gametocyte density and infection success in mosquitoes; implications for the evaluation of malaria transmission-reducing interventions

The evaluation of transmission reducing interventions (TRI) to control malaria widely uses membrane feeding assays. In such assays, the intensity of Plasmodium infection in the vector might affect the measured efficacy of the candidates to block transmission. Gametocyte density in the host blood is a determinant of the infection success in the mosquito, however, uncertain estimates of parasite densities and intrinsic characteristics of the infected blood can induce variability. To reduce this variation, a feasible method is to dilute infectious blood samples. We describe the effect of diluting samples of Plasmodium-containing blood samples to allow accurate relative measures of gametocyte densities and their impact on mosquito infectivity and TRI efficacy. Natural Plasmodium falciparum samples were diluted to generate a wide range of parasite densities, and fed to Anopheles coluzzii mosquitoes. This was compared with parallel dilutions conducted on Plasmodium berghei infections. We examined how blood dilution influences the observed blocking activity of anti-Pbs28 monoclonal antibody using the P. berghei/Anopheles stephensi system.In the natural species combination P. falciparum/An. coluzzii, blood dilution using heat-inactivated, infected blood as diluents, revealed positive near linear relationships, between gametocyte densities and oocyst loads in the range tested. A similar relationship was observed in the P. berghei/An. stephensi system when using a similar dilution method. In contrast, diluting infected mice blood with fresh uninfected blood dramatically increases the infectiousness. This suggests that highly infected mice blood contains inhibitory factors or reduced blood moieties, which impede infection and may in turn, lead to misinterpretation when comparing individual TRI evaluation assays. In the lab system, the transmission blocking activity of an antibody specific for Pbs28 was confirmed to be density-dependent. This highlights the need to carefully interpret evaluations of TRI candidates, regarding gametocyte densities in the P. berghei/An. stephensi system.

Mosquito Akirin as a potential antigen for malaria control.

BackgroundThe control of vector-borne diseases is important to improve human and animal health worldwide. Malaria is one of the world’s deadliest diseases and is caused by protozoan parasites of the genus Plasmodium, which are transmitted by Anopheles spp. mosquitoes. Recent evidences using Subolesin (SUB) and Akirin (AKR) vaccines showed a reduction in the survival and/or fertility of blood-sucking ectoparasite vectors and the infection with vector-borne pathogens. These experiments suggested the possibility of using AKR for malaria control.MethodsThe role of AKR on Plasmodium berghei infection and on the fitness and reproduction of the main malaria vector, Anopheles gambiae was characterized by evaluating the effect of akr gene knockdown or vaccination with recombinant mosquito AKR on parasite infection levels, fertility and mortality of female mosquitoes.ResultsGene knockdown by RNA interference in mosquitoes suggested a role for akr in mosquito survival and fertility. Vaccination with recombinant Aedes albopictus AKR reduced parasite infection in mosquitoes fed on immunized mice when compared to controls.ConclusionsThese results showed that recombinant AKR could be used to develop vaccines for malaria control. If effective, AKR-based vaccines could be used to immunize wildlife reservoir hosts and/or humans to reduce the risk of pathogen transmission. However, these vaccines need to be evaluated under field conditions to characterize their effect on vector populations and pathogen infection and transmission.

Exacerbation of autoimmune neuro-inflammation in mice cured from blood-stage Plasmodium berghei infection.

The thymus plays an important role shaping the T cell repertoire in the periphery, partly, through the elimination of inflammatory auto-reactive cells. It has been shown that, during Plasmodium berghei infection, the thymus is rendered atrophic by the premature egress of CD4+CD8+ double-positive (DP) T cells to the periphery. To investigate whether autoimmune diseases are affected after Plasmodium berghei NK65 infection, we immunized C57BL/6 mice, which was previously infected with P.berghei NK65 and treated with chloroquine (CQ), with MOG35–55 peptide and the clinical course of Experimental Autoimmune Encephalomyelitis (EAE) was evaluated. Our results showed that NK65+CQ+EAE mice developed a more severe disease than control EAE mice. The same pattern of disease severity was observed in MOG35–55-immunized mice after adoptive transfer of P.berghei-elicited splenic DP-T cells. The higher frequency of IL-17+- and IFN-γ+-producing DP lymphocytes in the Central Nervous System of these mice suggests that immature lymphocytes contribute to disease worsening. To our knowledge, this is the first study to integrate the possible relationship between malaria and multiple sclerosis through the contribution of the thymus. Notwithstanding, further studies must be conducted to assert the relevance of malaria-induced thymic atrophy in the susceptibility and clinical course of other inflammatory autoimmune diseases.

Expression analysis of reactive oxygen species detoxifying enzyme genes in Anopheles stephensi during Plasmodium berghei midgut invasion

ObjectiveTo investigate the involvement of reactive oxygen species detoxification system in Anopheles stephensi during Plasmodium berghei midgut invasion. MethodsEight key reactive oxygen species metabolizing enzymes were cloned and characterized, and their expression was monitored in parasite-infected mosquitoes. ResultsSuperoxide anion detoxifying superoxide dismutases (Fe/Mn SOD, Cu/Zn SOD 2, Cu/Zn SOD 3A, and Cu/Zn SOD 3B) depicted varied expression patterns. Fe/Mn SOD expression declined, whereas Cu/Zn SOD expression was elevated in the infected mosquitoes. Peroxidases, catalase and glutathione peroxidase showed lack of induction in expression during the Plasmodium berghei infection. Further, expression of thioredoxin reductase increased in the infected mosquitoes, whereas gluthathione S-transferase levels decreased markedly. ConclusionsDetoxification enzymes may play a role in modulating host immunity and parasite transmission.

Antiplasmodial potential of homeopathic drugs Chelidonium and nosode against Plasmodium berghei infection.

Malaria remains a major global health concern in developing regions of the world. Homeopathy, a holistic system of medicine, has a lot to offer in protecting against malaria. In the present study, antimalarial efficacy of combination of two homeopathic drugs Chelidonium 30 and nosode 30 has been evaluated in vivo against Plasmodium berghei (P. berghei) infection using Peters 4-day test. Biochemical assays have been performed to assess the levels of hepatic and renal function biomarkers upon drug treatment using diagnostic kits. The combination of the drugs demonstrated considerable in vivo antimalarial activity with chemosuppression of 91.45% on day 7. The combination also significantly (p < 0.0005) enhanced the mean survival time of mice which was calculated to be 22.5 ± 6.31 days, whereas it was 8.55 ± 0.83 days in infected control. The increase in levels of the liver function marker enzymes tested in serum of treated mice were significantly less (p < 0.0005) than those observed in infected control on day 10. The serum urea and creatinine used for assessment of renal sufficiency were slightly elevated above normal, but were statistically significant (p < 0.0005) as compared to infected control. The study establishes the effectiveness of the combination against P. berghei in vivo along with the safety of the drugs to the liver and kidney functions of the host.

Innexin AGAP001476 is critical for mediating anti-Plasmodium responses in Anopheles mosquitoes.

The Toll and IMD pathways are known to be induced upon Plasmodium berghei and Plasmodium falciparum infection, respectively. It is unclear how Plasmodium or other pathogens in the blood meal and their invasion of the midgut epithelium would trigger the innate immune responses in immune cells, in particular hemocytes. Gap junctions, which can mediate both cell-to-cell and cell-to-extracellular communication, may participate in this signal transduction. This study examined whether innexins, gap junction proteins in insects, are involved in anti-Plasmodium responses in Anopheles gambiae. Inhibitor studies using carbenoxolone indicated that blocking innexons resulted in an increase in Plasmodium oocyst number and infection prevalence. This was accompanied by a decline in TEP1 levels in carbenoxolone-treated mosquitoes. Innexin AGAP001476 mRNA levels in midguts were induced during Plasmodium infection and a knockdown of AGAP001476, but not AGAP006241, caused an induction in oocyst number. Silencing AGAP001476 caused a concurrent increase in vitellogenin levels, a TEP1 inhibitor, in addition to a reduced level of TEP1-LRIM1-APL1C complex in hemolymph. Both vitellogenin and TEP1 are regulated by Cactus under the Toll pathway. Simultaneous knockdown of cactus and AGAP001476 failed to reverse the near refractoriness induced by the knockdown of cactus, suggesting that the AGAP001476-mediated anti-Plasmodium response is Cactus-dependent. These data demonstrate a critical role for innexin AGAP001476 in mediating innate immune responses against Plasmodium through Toll pathway in mosquitoes.

Effect of &lt;em&gt;Acalypha wilkesiana&lt;/em&gt; MuellArg Leaf Extract on the Oxidative Indices, Liver Enzymes and Liver Integrity of Rats Infected with &lt;em&gt;Plasmodium berghei&lt;/em&gt;

This study investigates the effect of the methanolic extract of Acalypha wilkesiana on the oxidative stress caused by Plasmodium berghei infection and on the liver of parasitized animals. Phytochemical screening of the extract reveals that it is rich in flavonoids, carotenoids and sterols. Our results showed that liver Malondialdehyde (MDA) significantly (p<0.05) increased while Superoxide Dismutase (SOD), (Glutathione peroxide) GSH-P, reduced Glutathione (rGSH) and Catalase (CAT) decreased (p<0.05) in the parasitized non-treated rats, evident of increase in lipid peroxidation and oxidative stress following P. berghei infection. Extract treatment of the parasitized rats was observed to reverse the effects of the oxidative stress and restore the elevated liver enzymes; on the other hand, extract treatment of the non-parasitized rats increased antioxidant molecule levels, thus increasing their free radicals scavenging activity. The extract was also observed to extend the mean survival time of treated rats and improve malaria symptoms. Histological examination of the liver of treated and non-treated animals reveals that the extract may have a hepato-protective as there were no observable cellular defects. These findings suggest that the extract can be useful in management of oxidative stress to the biological system e.g., during malaria infection.

English

Antimalarial activity of the crude aqueous leaf extract of&nbsp;Pyrenacantha&nbsp;staudtii&nbsp;was evaluated using chloroquine-sensitive&nbsp;Plasmodium&nbsp;berghei&nbsp;infection in mice with an objective to finding scientific evidence for the use of the plant as traditional antimalarial remedy in Ido/Osi LGA of Ekiti state, Nigeria. The crude aqueous extract of&nbsp;P.&nbsp;staudtii&nbsp;Engl. (Icacinaceae) (100, 200 and 500 mg/kg) was administered orally to mice infected with&nbsp;P.&nbsp;berghei&nbsp;in 4 days suppressive test. The antiplasmodial effect during the test of the plant in blood was determined and the extract at these doses induced 58.0 to 63.4% activity in comparison with untreated (negative) control group. Chloroquine produced 100% activity. The antimalarial activity showed by&nbsp;P.&nbsp;staudtii&nbsp;during the test justifies its use in traditional medicine for treating of malaria in the area. &nbsp; Key words:&nbsp;Pyrenacantha&nbsp;staudtii,&nbsp;herb, malarial, anti-malarial, Ido/Osi, Ekiti,&nbsp;Plasmodium berghei, mice.

Production, Fate and Pathogenicity of Plasma Microparticles in Murine Cerebral Malaria

In patients with cerebral malaria (CM), higher levels of cell-specific microparticles (MP) correlate with the presence of neurological symptoms. MP are submicron plasma membrane-derived vesicles that express antigens of their cell of origin and phosphatidylserine (PS) on their surface, facilitating their role in coagulation, inflammation and cell adhesion. In this study, the in vivo production, fate and pathogenicity of cell-specific MP during Plasmodium berghei infection of mice were evaluated. Using annexin V, a PS ligand, and flow cytometry, analysis of platelet-free plasma from infected mice with cerebral involvement showed a peak of MP levels at the time of the neurological onset. Phenotypic analyses showed that MP from infected mice were predominantly of platelet, endothelial and erythrocytic origins. To determine the in vivo fate of MP, we adoptively transferred fluorescently labelled MP from mice with CM into healthy or infected recipient mice. MP were quickly cleared following intravenous injection, but microscopic examination revealed arrested MP lining the endothelium of brain vessels of infected, but not healthy, recipient mice. To determine the pathogenicity of MP, we transferred MP from activated endothelial cells into healthy recipient mice and this induced CM-like brain and lung pathology. This study supports a pathogenic role for MP in the aggravation of the neurological lesion and suggests a causal relationship between MP and the development of CM.