Pre-erythrocytic Stage of Mammalian Malaria

Shortt, H. E.; Garnhám, P. C. C.; Malamos, B.

doi:10.1136/bmj.1.4543.192

Cited by 48 publications

(12 citation statements)

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“…Regarding Plasmodium parasite growth, the sizes reported in our system are similar to what have been previously observed in other in vitro systems at day 5 32,66,74 , but smaller than those observed observed in vivo at day 5 75,76 or in humanized mouse models 77 . It is possible that conformational cues may be important for parasite growth (e.g., two-dimensional versus three-dimensional contexts), or that EEF size is impacted by hepatocyte packing density.…”

Section: Introductionsupporting

confidence: 89%

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Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

et al. 2015

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Studying human hepatotropic pathogens such as hepatitis B and C viruses and malaria will be necessary for understanding host-pathogen interactions, and developing therapy and prophylaxis. Unfortunately, existing in vitro liver models typically employ either cell lines that exhibit aberrant physiology, or primary human hepatocytes in culture configurations wherein they rapidly lose their hepatic functional phenotype. Stable, robust, and reliable in vitro primary human hepatocyte models are needed as platforms for infectious disease applications. For this purpose, we describe the application of micropatterned co-cultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive cells. Using this system, we demonstrate how to recapitulate in vitro liver infection by the hepatitis B and C viruses and Plasmodium pathogens. In turn, the MPCC platform can be used to uncover aspects of host-pathogen interactions, and has the potential to be used for medium-throughput drug screening and vaccine development.

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Section: Introductionsupporting

confidence: 89%

“…However, larger EEFs have been observed in vivo at day 5 (30-50 μm) 75,76 or in humanized mouse models (18-22 μm at day 5 and 54-69 μm at day 7) 77 . Nonetheless, we consistently observe that P. falciparum EEFs continue to grow in MPCCs for at least 7 days post infection 16 .…”

Section: Anticipated Resultsmentioning

confidence: 99%

Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

et al. 2015

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“…Plasmodium species and mammals have coexisted for millions of years, with frequent cases of host-shifts and host range expansions along their evolution [38, 39]. Great apes are commonly infected with malaria-related parasites [40, 41] and recent evidence suggests that human P. vivax originated in African great apes [40], contrasting with previous results that supported an Asian origin for P. vivax [42, 43].…”

Section: Introductionmentioning

confidence: 99%

Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

et al. 2017

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The human DARC (Duffy antigen receptor for chemokines) gene encodes a membrane-bound chemokine receptor crucial for the infection of red blood cells by Plasmodium vivax, a major causative agent of malaria. Of the three major allelic classes segregating in human populations, the FY*O allele has been shown to protect against P. vivax infection and is at near fixation in sub-Saharan Africa, while FY*B and FY*A are common in Europe and Asia, respectively. Due to the combination of strong geographic differentiation and association with malaria resistance, DARC is considered a canonical example of positive selection in humans. Despite this, details of the timing and mode of selection at DARC remain poorly understood. Here, we use sequencing data from over 1,000 individuals in twenty-one human populations, as well as ancient human genomes, to perform a fine-scale investigation of the evolutionary history of DARC. We estimate the time to most recent common ancestor (TMRCA) of the most common FY*O haplotype to be 42 kya (95% CI: 34–49 kya). We infer the FY*O null mutation swept to fixation in Africa from standing variation with very low initial frequency (0.1%) and a selection coefficient of 0.043 (95% CI:0.011–0.18), which is among the strongest estimated in the human genome. We estimate the TMRCA of the FY*A mutation in non-Africans to be 57 kya (95% CI: 48–65 kya) and infer that, prior to the sweep of FY*O, all three alleles were segregating in Africa, as highly diverged populations from Asia and ≠Khomani San hunter-gatherers share the same FY*A haplotypes. We test multiple models of admixture that may account for this observation and reject recent Asian or European admixture as the cause.

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“…The hepatic effector cells present in challenged mice could mediate a memory T cell response in the liver. Shortt et al, in 1948 observed that an immune volunteer infected with sporozoites of P. vivax did not develop any blood infection but had hepatic schizonts surrounded by infiltrated cells (Shortt et al 1948). This was confirmed in a simian model by Garnham and Bray (Garnham & Bray 1956).…”

Section: Discussionmentioning

confidence: 99%

Protective immunity against malaria: cellular changes in the liver vary according to the method of immunization

Fauré

Hulier

Miltgen

et al. 1995

Parasite Immunology

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Characterization of cells present in the extravascular compartment of murine liver was performed after different immunization procedures against the malaria parasite Plasmodium yoelii. Mice were immunized with live or irradiated sporozoites or with parasitized erythrocytes. Whatever the immunization protocol used, the mice were protected against a sporozoite challenge but each immunization procedure induced a specific profile of cell types. Immunization with irradiated sporozoite induce a significant increase in CD8+ lymphocytes, parasitized erythrocytes stimulates production of monocytes/macrophages and CD8+ lymphocytes while, after live sporozoites immunization, polymorphonuclear cells, macrophages/monocytes, B cells and a range of T cell subsets were increased in number.

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Pre-erythrocytic Stage of Mammalian Malaria

Cited by 48 publications

References 1 publication

Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens

Population genetic analysis of the DARC locus (Duffy) reveals adaptation from standing variation associated with malaria resistance in humans

Protective immunity against malaria: cellular changes in the liver vary according to the method of immunization

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