Mouse Models of Uncomplicated and Fatal Malaria

Huang, Ben; Pearman, Emily; Kim, Charles C.

doi:10.21769/bioprotoc.1514

Cited by 38 publications

(51 citation statements)

References 9 publications

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“…Mice were infected with 10 6 Plasmodium chabaudi AS (MRA-429; MR4 Stock Center) parasitized RBCs, and parasitemia was monitored by thin film blood smear as described [86]. Where noted, mice were injected i.p.…”

Section: Methodsmentioning

confidence: 99%

Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection

et al. 2016

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Dynamic regulation of leukocyte population size and activation state is crucial for an effective immune response. In malaria, Plasmodium parasites elicit robust host expansion of macrophages and monocytes, but the underlying mechanisms remain unclear. Here we show that myeloid expansion during P. chabaudi infection is dependent upon both CD4+ T cells and the cytokine Macrophage Colony Stimulating Factor (MCSF). Single-cell RNA-Seq analysis on antigen-experienced T cells revealed robust expression of Csf1, the gene encoding MCSF, in a sub-population of CD4+ T cells with distinct transcriptional and surface phenotypes. Selective deletion of Csf1 in CD4+ cells during P. chabaudi infection diminished proliferation and activation of certain myeloid subsets, most notably lymph node-resident CD169+ macrophages, and resulted in increased parasite burden and impaired recovery of infected mice. Depletion of CD169+ macrophages during infection also led to increased parasitemia and significant host mortality, confirming a previously unappreciated role for these cells in control of P. chabaudi. This work establishes the CD4+ T cell as a physiologically relevant source of MCSF in vivo; probes the complexity of the CD4+ T cell response during type 1 infection; and delineates a novel mechanism by which T helper cells regulate myeloid cells to limit growth of a blood-borne intracellular pathogen.

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Section: Methodsmentioning

confidence: 99%

Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection

et al. 2016

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“…Parasite suppression and antimalarial effect of the lemon decoction as evaluated using Rane's curative test employing Plasmodium berghei parasites. Is an good model for studying pathological features associated with malaria infections as well as the primary screening for natural products with antimalarial activity [21]. In this study lemon decoction (CILI extract) has shown some antimalarial effect by suppressing parasite growth as depicted in Table 3.…”

Section: Discussionmentioning

confidence: 92%

Effects of lemon decoction on malaria parasite clearance and selected hematological parameters in Plasmodium berghei ANKA infected mice

Shija

Nondo

Mloka

et al. 2020

BMC Complement Med Ther

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Background: Citrus plants particularly lemon (Citrus limon L.) concoctions are ethno-medically used for treatment of infectious diseases including malaria. Therefore, we set an experiment to investigate the effects of lemon decoction in mice infected with Plasmodium berghei ANKA parasites. Methods: Antimalarial activity was determined using Rane's curative test on 25 Theiler's albino mice. Twenty mice were each injected with 2 × 10 7 infected red blood cells (iRBCs). The mice were divided into four groups, consisting of five mice per group. Each group received an oral dose of either 5% carboxymethyl cellulose/placebo (negative infected control), lemon decoction (Citrus limon [CILI extract]) alone or a combination of artemether/lumefantrine (A/LU, 28 mg/kg) and CILI extract and A/LU alone. A fifth group of mice consisted of uninfected mice as parasitenegative control. Results: Within 72 hours after initiation of treatment, the mean percentage parasitemia ± standard deviation of the CILI extract group (24.2% ± 9.83%) was lower compared to placebo group (40.0% ± 14.78%), p = 0.037. CILI extract group was found to have an increased survival rate (11 days ± 1.6 days) as compared to placebo group (8.6 days ± 3.4 days), p = 0.226. Mice in the combination group (A/LU + CILI extract) had the highest mean counts in terms of hemato-immunological parameters, whereas those in the CILI extract alone had the lowest hematocrit levels. The study also found that mice that received a combination of CILI extract and A/LU exhibited a decreased lag time with regards to time required to clear 99% of parasites (58.8 h vs. 64.2 h, p = 0.681) as compared to the A/LU alone group. Conclusion: Lemon decoction demonstrated antimalarial activity in mice infected with P. berghei ANKA through parasites suppression by 39% as compared to those received placebo. However, when used alone, lemons did not suffice as a cure but in combination with standard antimalarials, lemons promoted early parasite clearance with an improved hematological parameters.

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“…Toxoplasma gondii is frequently used as a model organism for other apicomplexa due to its genetic and biochemical manipulability (Li and He 2017; Meyer, Caton, and Shapiro 2018; Sidik et al 2016; Kim and Weiss 2004). Mouse models of malaria (Huang, Pearman, and Kim 2015; Minkah, Schafer, and Kappe 2018) and cryptosporidiosis (Ward 2017; Sateriale et al 2019) imperfectly represent the disease and/or use different species than the human pathogen. However, the modest characterization of functional differences among parasite species limits the utility of this extrapolation-based approach.…”

Section: Introductionmentioning

confidence: 99%

Comparative analyses of parasites with a comprehensive database of genome-scale metabolic models

Carey

Medlock

Stolarczyk

et al. 2019

Preprint

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1 Protozoan parasites cause diverse diseases with large global impacts. Research on the pathogenesis and biology 2 of these organisms is limited by economic and experimental constraints. Accordingly, studies of one parasite are 3 frequently extrapolated to infer knowledge about another parasite, across and within genera. Model in vitro or in 4 vivo systems are frequently used to enhance experimental manipulability, but these systems generally use species 5 related to, yet distinct from, the clinically relevant causal pathogen. Characterization of functional differences 6 among parasite species is confined to post hoc or single target studies, limiting the utility of this extrapolation 7 approach. To address this challenge and to accelerate parasitology research broadly, we present a functional 8 comparative analysis of 192 genomes, representing every high-quality, publicly-available protozoan parasite 9 genome including Plasmodium, 10 and other species. We generated an automated metabolic network reconstruction pipeline optimized for 11 eukaryotic organisms. These metabolic network reconstructions serve as biochemical knowledgebases for each 12 parasite, enabling qualitative and quantitative comparisons of metabolic behavior across parasites. We identified 13 putative differences in gene essentiality and pathway utilization to facilitate the comparison of experimental 14 findings. This knowledgebase represents the largest collection of genome-scale metabolic models for both 15 pathogens and eukaryotes; with this resource, we can predict species-specific functions, contextualize 16 experimental results, and optimize selection of experimental systems for fastidious species. 42hindering drug development, such as resistance to genetic modification. For example, Plasmodium falciparum 43 (malaria) was considered refractory to genetic modification until recently (Ghorbal et al. 2014; Lee and Fidock 44 2014). Entamoeba histolytica (diarrheal disease) has also been refractory to efficient genetic manipulation, and the genomes of Leishmania develop significant aneuploidy under selective pressure (Downing et al. 2011; Sterkers Although these challenges may be circumvented with new technology, the use of clinical samples, and reductionist 1 approaches, little data exist relative to that which is available for most bacterial pathogens. Without adequate 2 profiling data (genome-wide essentiality, growth profiling in diverse environmental conditions, etc.), we do not 3 have the knowledge to rationally identify novel drug targets. Untargeted and unbiased screens of chemical 4 compounds for antiparasitic effects have proven useful (if the parasite can be cultured, e.g. (Jumani et al. 2018; 5 Chao et al. 2018; Love et al. 2017; Subramanian et al. 2018; Lucantoni et al. 2013)), but this approach provides 6 little information about mechanism of action or mechanisms of resistance development. Typical approaches to 7 study drug resistance, such as evolving resistance to identify mutations in a drug's putative target, are not poss...

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Mouse Models of Uncomplicated and Fatal Malaria

Cited by 38 publications

References 9 publications

Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection

Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection

Effects of lemon decoction on malaria parasite clearance and selected hematological parameters in Plasmodium berghei ANKA infected mice

Comparative analyses of parasites with a comprehensive database of genome-scale metabolic models

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