Prenatal immune responses to Plasmodium falciparum erythrocyte membrane protein 1 DBL-α domain in Gabon

Tena-Tomás, Cristina; Bouyou-Akotet, Marielle Karine; Kendjo, Éric; Kombila, Maryvonne; Kremsner, Peter G.; Kun, Jürgen F. J.

doi:10.1007/s00436-007-0585-9

Cited by 7 publications

(7 citation statements)

References 21 publications

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“…This hypothesis is further strengthened by reports of non-immune HbS children with high parasitemias and severe malaria [36], and could be more rigorously tested by studying non-immune hemoglobinopathic individuals who acquire malaria. Our findings indicate that measurements of PfEMP-1-specific antibody levels are likely to be particularly relevant and informative in studies of infant immunity to malaria [37], [38], [39].…”

Section: Discussionmentioning

confidence: 86%

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

et al. 2011

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BackgroundIn Africa, infant susceptibility to Plasmodium falciparum malaria increases substantially as fetal hemoglobin (HbF) and maternal immune IgG disappear from circulation. During the first few months of life, however, resistance to malaria is evidenced by extremely low parasitemias, the absence of fever, and the almost complete lack of severe disease. This resistance has previously been attributed in part to poor parasite growth in HbF-containing red blood cells (RBCs). A specific role for maternal immune IgG in infant resistance to malaria has been hypothesized but not yet identified.Methods and FindingsWe found that P. falciparum parasites invade and develop normally in fetal (cord blood, CB) RBCs, which contain up to 95% HbF. However, these parasitized CB RBCs are impaired in their binding to human microvascular endothelial cells (MVECs), monocytes, and nonparasitized RBCs – cytoadherence interactions that have been implicated in the development of high parasite densities and the symptoms of malaria. Abnormal display of the parasite's cytoadherence antigen P. falciparum erythrocyte membrane protein-1 (PfEMP-1) on CB RBCs accounts for these findings and is reminiscent of that on HbC and HbS RBCs. IgG purified from the plasma of immune Malian adults almost completely abolishes the adherence of parasitized CB RBCs to MVECs.ConclusionsOur data suggest a model of malaria protection in which HbF and maternal IgG act cooperatively to impair the cytoadherence of parasitized RBCs in the first few months of life. In highly malarious areas of Africa, an infant's contemporaneous expression of HbC or HbS and development of an immune IgG repertoire may effectively reconstitute the waning protective effects of HbF and maternal immune IgG, thereby extending the malaria resistance of infancy into early childhood.

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Section: Discussionmentioning

confidence: 86%

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

et al. 2011

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“…As maternal IgM (and likely IgE) do not cross the placental barrier, detection of malaria‐specific IgM and/or IgE in cord blood may also provide evidence that infants have antigen‐specific B cells capable of producing antibody. Although some studies have reported minimal detection of P. falciparum ‐specific IgM in cord blood, others have reported P. falciparum ‐specific IgM in up to 30% of African newborns . In addition, Desowitz et al reported detection of malaria‐specific IgE in cord blood.…”

Section: Altered Malaria‐specific Immune Responses In Cord Bloodmentioning

confidence: 99%

Malaria in pregnancy shapes the development of foetal and infant immunity

Harrington

Kakuru

Jagannathan

2018

Parasite Immunology

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Malaria, particularly Plasmodium falciparum, continues to disproportionately affect pregnant women. In addition to the profoundly deleterious impact of maternal malaria on the health of the mother and foetus, malaria infection in pregnancy has been shown to affect the development of the foetal and infant immune system and may alter the risk of malaria and nonmalarial outcomes during infancy. This review summarizes our current understanding of how malaria infection in pregnancy shapes the protective components of the maternal immune system transferred to the foetus and how foetal exposure to parasite antigens impacts the development of foetal and infant immunity. It also reviews existing evidence linking malaria infection in pregnancy to malaria and nonmalarial outcomes in infancy and how preventing malaria in pregnancy may alter these outcomes. A better understanding of the consequences of malaria infection in pregnancy on the development of foetal and infant immunity will inform control strategies, including intermittent preventive treatment in pregnancy and vaccine development.

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“…The nature of the initial exposure to malaria Ags likely affects the potentially diverse roles assumed by T regs in malaria infection. For some individuals, this first experience appears to occur in utero (10,12,14,17,83,84). This may have an important impact on the subsequent development of an individual's immune response to malaria and potentially to other Ags.…”

Section: Cd25mentioning

confidence: 99%

Human Cord Blood CD4+CD25hi Regulatory T Cells Suppress Prenatally Acquired T Cell Responses toPlasmodium falciparumAntigens

Mackroth

Malhotra

Mungai

et al. 2011

The Journal of Immunology

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In malaria endemic regions, a fetus is often exposed in utero to Plasmodium falciparum blood-stage Ags. In some newborns, this can result in the induction of immune suppression. We have previously shown these modulated immune responses to persist postnatally, with a subsequent increase in a child’s susceptibility to infection. To test the hypothesis that this immune suppression is partially mediated by malaria-specific regulatory T cells (Tregs) in utero, cord blood mononuclear cells (CBMC) were obtained from 44 Kenyan newborns of women with and without malaria at delivery. CD4+CD25lo T cells and CD4+CD25hi FOXP3+ cells (Tregs) were enriched from CBMC. Treg frequency and HLA-DR expression on Tregs were significantly greater for Kenyan as compared with North American CBMC (p < 0.01). CBMC/CD4+ T cells cultured with P. falciparum blood-stage Ags induced production of IFN-γ, IL-13, IL-10, and/or IL-5 in 50% of samples. Partial depletion of CD25hi cells augmented the Ag-driven IFN-γ production in 69% of subjects with malaria-specific responses and revealed additional Ag-reactive lymphocytes in previously unresponsive individuals (n = 3). Addition of Tregs to CD4+CD25lo cells suppressed spontaneous and malaria Ag-driven production of IFN-γ in a dose-dependent fashion, until production was completely inhibited in most subjects. In contrast, Tregs only partially suppressed malaria-induced Th2 cytokines. IL-10 or TGF-β did not mediate this suppression. Thus, prenatal exposure to malaria blood-stage Ags induces Tregs that primarily suppress Th1-type recall responses to P. falciparum blood-stage Ags. Persistence of these Tregs postnatally could modify a child’s susceptibility to malaria infection and disease.

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Prenatal immune responses to Plasmodium falciparum erythrocyte membrane protein 1 DBL-α domain in Gabon

Cited by 7 publications

References 21 publications

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria

Malaria in pregnancy shapes the development of foetal and infant immunity

Human Cord Blood CD4+CD25hi Regulatory T Cells Suppress Prenatally Acquired T Cell Responses toPlasmodium falciparumAntigens

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