• Title/Summary/Keyword: Plasmodium berghei

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Previous Infection with Plasmodium berghei Confers Resistance to Toxoplasma gondii Infection in Mice

  • Lee, Dong-Hun;Chu, Ki-Back;Kang, Hae-Ji;Lee, Su-Hwa;Quan, Fu-Shi
    • Parasites, Hosts and Diseases
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    • v.57 no.2
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    • pp.93-99
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    • 2019
  • Both Plasmodium spp. and Toxoplasma gondii are important apicomplexan parasites, which infect humans worldwide. Genetic analyses have revealed that 33% of amino acid sequences of inner membrane complex from the malaria parasite Plasmodium berghei is similar to that of Toxoplasma gondii. Inner membrane complex is known to be involved in cell invasion and replication. In this study, we investigated the resistance against T. gondii (ME49) infection induced by previously infected P. berghei (ANKA) in mice. Levels of T. gondii-specific IgG, IgG1, IgG2a, and IgG2b antibody responses, $CD4^+$ and $CD8^+$ T cell populations were found higher in the mice infected with P. berghei (ANKA) and challenged with T. gondii (ME49) compared to that in control mice infected with T. gondii alone (ME49). P. berghei (ANKA) + T. gondii (ME49) group showed significantly reduced the number and size of T. gondii (ME49) cysts in the brains of mice, resulting in lower body weight loss compared to ME49 control group. These results indicate that previous exposure to P. berghei (ANKA) induce resistance to subsequent T. gondii (ME49) infection.

Glutathione Reductase and Thioredoxin Reductase: Novel Antioxidant Enzymes from Plasmodium berghei

  • Kapoor, Gaurav;Banyal, Harjeet Singh
    • Parasites, Hosts and Diseases
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    • v.47 no.4
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    • pp.421-424
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    • 2009
  • Malaria parasites adapt to the oxidative stress during their erythrocytic stages with the help of vital thioredoxin redox system and glutathione redox system. Glutathione reductase and thioredoxin reductase are important enzymes of these redox systems that help parasites to maintain an adequate intracellular redox environment. In the present study, activities of glutathione reductase and thioredoxin reductase were investigated in normal and Plasmodium berghei-infected mice red blood cells and their fractions. Activities of glutathione reductase and thioredoxin reductase in P. berghei-infected host erythrocytes were found to be higher than those in normal host cells. These enzymes were mainly confined to the cytosolic part of cell-free P. berghei. Full characterization and understanding of these enzymes may promise advances in chemotherapy of malaria.

Glutamate dehydrogenase antigen detection in Plasmodium falciparum infections

  • Dominguez, Neira-De;Alexis, Rodriguez-Acosta
    • Parasites, Hosts and Diseases
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    • v.34 no.4
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    • pp.239-246
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    • 1996
  • The usefulness of malaria diagnosis by Plusmodium JaLcipawn-GDH (NADP+), obtained by affinity chromatography. is demonstrated in ELISA assays, testing IgG antibodies against GDH (NADP+) from patients with acute malaria, who have had two or more episodes of malaria. or from sera of hyperimmune patients. GDH (NADP+) thermal stability was demonstrated in a high heat resistance assay. The immunofluorescence assay demonstrated that anti-culture (P. falciporum) supernatant serum and anti-GDH (NADP+) of Proton app. recognized epitopes in Venezuelan isolates and Colombian and Brazilian malarial strains. The antigen is soluble, with high specificity is a potent imnlunogen and is thermoresistant. Key words: antigenic enzymes. glutamate dehydrogenase, malaria diagnosis, Plasmodium berghei, Plcswlodium ccthemelum, PlusmoniumJnlcipnmm, Plosmonium uiuox. soluble antigens.

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Characterization of Plasmodium berghei Homologues of T-cell Immunomodulatory Protein as a New Potential Candidate for Protecting against Experimental Cerebral Malaria

  • Cui, Ai;Li, Yucen;Zhou, Xia;Wang, Lin;Luo, Enjie
    • Parasites, Hosts and Diseases
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    • v.57 no.2
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    • pp.101-115
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    • 2019
  • The pathogenesis of cerebral malaria is biologically complex and involves multi-factorial mechanisms such as microvascular congestion, immunopathology by the pro-inflammatory cytokine and endothelial dysfunction. Recent data have suggested that a pleiotropic T-cell immunomodulatory protein (TIP) could effectively mediate inflammatory cytokines of mammalian immune response against acute graft-versus-host disease in animal models. In this study, we identified a conserved homologue of TIP in Plasmodium berghei (PbTIP) as a membrane protein in Plasmodium asexual stage. Compared with PBS control group, the pathology of experimental cerebral malaria (ECM) in rPbTIP intravenous injection (i.v.) group was alleviated by the downregulation of pro-inflammatory responses, and rPbTIP i.v. group elicited an expansion of regulatory T-cell response. Therefore, rPbTIP i.v. group displayed less severe brain pathology and feverish mice in rPbTIP i.v. group died from ECM. This study suggested that PbTIP may be a novel promising target to alleviate the severity of ECM.

Expressed Sequence Tag Analysis of the Erythrocytic Stage of Plasmodium berghei

  • Seok, Ji-Woong;Lee, Yong-Seok;Moon, Eun-Kyung;Lee, Jung-Yub;Jha, Bijay Kumar;Kong, Hyun-Hee;Chung, Dong-Il;Hong, Yeon-Chul
    • Parasites, Hosts and Diseases
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    • v.49 no.3
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    • pp.221-228
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    • 2011
  • Rodent malaria parasites, such as Plasmodium berghei, are practical and useful model organisms for human malaria research because of their analogies to the human malaria in terms of structure, physiology, and life cycle. Exploiting the available genetic sequence information, we constructed a cDNA library from the erythrocytic stages of P. berghei and analyzed the expressed sequence tag (EST). A total of 10,040 ESTs were generated and assembled into 2,462 clusters. These EST clusters were compared against public protein databases and 48 putative new transcripts, most of which were hypothetical proteins with unknown function, were identified. Genes encoding ribosomal or membrane proteins and purine nucleotide phosphorylases were highly abundant clusters in P. berghei. Protein domain analyses and the Gene Ontology functional categorization revealed translation/protein folding, metabolism, protein degradation, and multiple family of variant antigens to be mainly prevalent. The presently-collected ESTs and its bioinformatic analysis will be useful resources to identify for drug target and vaccine candidates and validate gene predictions of P. berghei.

Antimalarial Efficacy of Aqueous Extract of Strychnos ligustrina and Its Combination with Dihydroartemisinin and Piperaquine Phosphate (DHP) against Plasmodium berghei Infection

  • Cahyaningsih, Umi;Sa'diah, Siti;Syafii, Wasrin;Sari, Rita Kartika;Maring, Abdul Jafar;Nugraha, Arifin Budiman
    • Parasites, Hosts and Diseases
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    • v.60 no.5
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    • pp.339-344
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    • 2022
  • The development of drug resistance is one of the most severe concerns of malaria control because it increases the risk of malaria morbidity and death. A new candidate drug with antiplasmodial activity is urgently needed. This study evaluated the efficacy of different dosages of aqueous extract of Strychnos ligustrina combined with dihydroartemisinin and piperaquine phosphate (DHP) against murine Plasmodium berghei infection. The BALB/c mice aged 6-8 weeks were divided into 6 groups, each consisting of 10 mice. The growth inhibition of compounds against P. berghei was monitored by calculating the percentage of parasitemia. The results showed that the mice receiving aqueous extract and combination treatment showed growth inhibition of P. berghei in 74% and 94%, respectively. S. ligustrina extract, which consisted of brucine and strychnine, effectively inhibited the multiplication of P. berghei. The treated mice showed improved hematology profiles, body weight, and temperature, as compared to control mice. Co-treatment with S. ligustrina extract and DHP revealed significant antimalarial and antipyretic effects. Our results provide prospects for further discovery of antimalarial drugs that may show more successful chemotherapeutic treatment.

Evaluation of the antimalarial activity of SAM13-2HCl with morpholine amide (SKM13 derivative) against antimalarial drug-resistant Plasmodium falciparum and Plasmodium berghei infected ICR mice

  • Hyelee Hong;Kwonmo Moon;Thuy-Tien Thi Trinh;Tae-Hui Eom;Hyun Park;Hak Sung Kim;Seon-Ju Yeo
    • Parasites, Hosts and Diseases
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    • v.62 no.1
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    • pp.42-52
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    • 2024
  • Antimalarial drugs are an urgently need and crucial tool in the campaign against malaria, which can threaten public health. In this study, we examined the cytotoxicity of the 9 antimalarial compounds chemically synthesized using SKM13-2HCl. Except for SKM13-2HCl, the 5 newly synthesized compounds had a 50% cytotoxic concentration (CC50) >100 μM, indicating that they would be less cytotoxic than SKM13-2HCl. Among the 5 compounds, only SAM13-2HCl outperformed SKM13-2HCl for antimalarial activity, showing a 3- and 1.3-fold greater selective index (SI) (CC50/IC50) than SKM13-2HCl in vitro against both chloroquine-sensitive (3D7) and chloroquine -resistant (K1) Plasmodium falciparum strains, respectively. Thus, the presence of morpholine amide may help to effectively suppress human-infectious P. falciparum parasites. However, the antimalarial activity of SAM13-2HCl was inferior to that of the SKM13-2HCl template compound in the P. berghei NK65-infected mouse model, possibly because SAM13-2HCl had a lower polarity and less efficient pharmacokinetics than SKM13-2HCl. SAM13-2HCl was more toxic in the rodent model. Consequently, SAM13-2HCl containing morpholine was selected from screening a combination of pharmacologically significant structures as being the most effective in vitro against human-infectious P. falciparum but was less efficient in vivo in a P. berghei-infected animal model when compared with SKM13-2HCl. Therefore, SAM13-2HCl containing morpholine could be considered a promising compound to treat chloroquine-resistant P. falciparum infections, although further optimization is crucial to maintain antimalarial activity while reducing toxicity in animals.

Age-Related $CD4^+CD25^+Foxp3^+$ Regulatory T-Cell Responses During Plasmodium berghei ANKA Infection in Mice Susceptible or Resistant to Cerebral Malaria

  • Shan, Ying;Liu, Jun;Pan, Yan-Yan;Jiang, Yong-Jun;Shang, Hong;Cao, Ya-Ming
    • Parasites, Hosts and Diseases
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    • v.51 no.3
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    • pp.289-295
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    • 2013
  • Different functions have been attributed to $CD4^+CD25^+Foxp3^+$ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-${\alpha}$, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.