Fetal hemoglobin does not inhibit Plasmodium falciparum growth

Archer, Natasha M.; Petersen, Nicole; Duraisingh, Manoj T.

doi:10.1182/bloodadvances.2019000399

Cited by 11 publications

(13 citation statements)

References 13 publications

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“…Furthermore, earlier reports suggested that Plasmodium parasites do not develop normally in red blood cells containing fetal hemoglobin ( Wilson et al., 1977 ). These data have been challenged by more recent study results that show that P. falciparum and P. vivax parasites invade cord blood-derived RBCs as well as RBCs from peripheral blood ( Archer et al., 2019 ; Roobsoong et al., 2015 ). Concordantly, the invasion capacity of the parasites in our model was not reduced in reticulocytes originating from cord blood.…”

Section: Discussionmentioning

confidence: 98%

A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

et al. 2020

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Summary The human malaria parasite Plasmodium vivax remains vastly understudied, mainly due to the lack of suitable laboratory models. Here, we report a humanized mouse model to test interventions that block P. vivax parasite transition from liver stage infection to blood stage infection. Human liver-chimeric FRGN huHep mice infected with P. vivax sporozoites were infused with human reticulocytes, allowing transition of exo-erythrocytic merozoites to reticulocyte infection and development into all erythrocytic forms, including gametocytes, in vivo. In order to test the utility of this model for preclinical assessment of interventions, the invasion blocking potential of a monoclonal antibody targeting the essential interaction of the P. vivax Duffy Binding Protein with the Duffy antigen receptor was tested by passive immunization. This antibody inhibited invasion by over 95%, providing unprecedented in vivo evidence that PvDBP constitutes a promising blood stage vaccine candidate and proving our model highly suitable to test blood stage interventions.

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Section: Discussionmentioning

confidence: 98%

A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

et al. 2020

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“…The delay in the onset of parasitemia in our experiments cannot be attributed to maternal antibodies because the dams were naïve to P. yoelii . Although early studies suggested the prevalence of HbF during neonatal period as another possible reason in the protection of infants from P. falciparum infection 16 , subsequent studies demonstrated that cord RBCs can be infected with P. falciparum 18 , 19 . Moreover, HbF cannot account for the suppressed parasitemia in NB mice because, unlike humans, mice RBCs do not have HbF 38 .…”

Section: Discussionmentioning

confidence: 99%

“…Early studies suggested that P. falciparum growth is arrested in cord blood erythrocytes due to HbF 16 , 17 . Subsequent reports demonstrated that Hbf does not inhibit P. falciparum growth in infant red blood cells 18 , 19 . The dietary elements of neonatal period can also be contributing to the protection of infants from malaria 20 .…”

Section: Introductionmentioning

confidence: 99%

Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning

Parra

Yang

Weitner

et al. 2021

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We developed a newborn (NB) mouse Plasmodium yoelii NL infection model to study malaria in early age. Surprisingly, the onset of parasitemia in P. yoelii challenged NB mice was delayed compared to adults and coincided with the weaning date when weanlings switched from maternal milk to normal chow diet. Also, compared to adult mice, parasitemia resolved much later (48 days vs 20 days post challenge) and the peak parasitemia was twice as high in weanlings. Concurrently, weanlings’ germinal center reaction was delayed and diminished compared to adult mice. Maternal milk is deficient in para-aminobenzoic acid (PABA), which is required for de novo folate synthesis by Plasmodium. Suggesting a possible role for the protection afforded by PABA-deficient maternal milk, mice fed with a PABA-deficient diet after the weaning continued to control parasitemia. Despite the reduced parasitemia, these mice developed robust T follicular helper (Tfh) responses and were protected from a second P. yoelii challenge. The NB malaria model provides mechanistic insight into the human infant malaria manifestations where a diet solely based on breast-feeding reduces the incidence of severe malaria in infants. NB mice experiments also support further studies to investigate dietary PABA restriction in the management of severe malaria in infants.

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“…There is also evidence that sickle red cells can modify the parasite gene expression at transcriptional level through red cell microRNA that translocate into the parasite (39). This raises the possibility that other abnormal hemoglobin, such as HbF, may as well contribute to protection by reducing var gene expression and cytoadhesion (40). HbF has been suggested to work together with maternally acquired antibodies to protect infants from malaria (41) perhaps by impairing cytoadhesion and promoting clearance of IE.…”

Section: Discussionmentioning

confidence: 99%

Exploring Plasmodium falciparum Var Gene Expression to Assess Host Selection Pressure on Parasites During Infancy

et al. 2019

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In sub-Saharan Africa, children below 5 years bear the greatest burden of severe malaria because they lack naturally acquired immunity that develops following repeated exposure to infections by Plasmodium falciparum. Antibodies to the surface of P. falciparum infected erythrocytes (IE) play an important role in this immunity. In children under the age of 6 months, relative protection from severe malaria is observed and this is thought to be partly due to trans-placental acquired protective maternal antibodies. However, the protective effect of maternal antibodies has not been fully established, especially the role of antibodies to variant surface antigens (VSA) expressed on IE. Here, we assessed the immune pressure on parasites infecting infants using markers associated with the acquisition of naturally acquired immunity to surface antigens. We hypothesized that, if maternal antibodies to VSA imposed a selection pressure on parasites, then the expression of a relatively conserved subset of var genes called group A var genes in infants should change with waning maternal antibodies. To test this, we compared their expression in parasites from children between 0 and 12 months and above 12 months of age. The transcript quantity and the proportional expression of group A var subgroup, including those containing domain cassette 13, were positively associated with age during the first year of life, which contrasts with above 12 months. This was accompanied by a decline in infected erythrocyte surface antibodies and an increase in parasitemia during this period. The observed increase in group A var gene expression with age in the first year of life, when the maternal antibodies are waning and before acquisition of naturally acquired antibodies with repeated exposure, is consistent with the idea that maternally acquired antibodies impose a selection pressure on parasites that infect infants and may play a role in protecting these infants against severe malaria.

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Fetal hemoglobin does not inhibit Plasmodium falciparum growth

Abstract: Key Points P falciparum growth is not inhibited in either cord or heterozygote hereditary persistence of fetal hemoglobin erythrocytes. P falciparum growth in fetal hemoglobin erythrocytes is oxygen independent.

Cited by 11 publications

References 13 publications

A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

A Humanized Mouse Model for Plasmodium vivax to Test Interventions that Block Liver Stage to Blood Stage Transition and Blood Stage Infection

Neonatal mice resist Plasmodium yoelii infection until exposed to para-aminobenzoic acid containing diet after weaning

Exploring Plasmodium falciparum Var Gene Expression to Assess Host Selection Pressure on Parasites During Infancy

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