Malaria Cellular Immune Responses in Neonates From Cameroon

Fiévet, Nadine; Ringwald, Pascal; Bickii, Jean; Dubois, Betty Lou; Maubert, Bertrand; Hesran, Jean-Yves Le; Cot, Michel; Deloron, Philippe

doi:10.1046/j.1365-3024.1996.d01-19.x

Cited by 65 publications

(60 citation statements)

References 21 publications

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“…IgM Abs reactive with a large number of blood stage Ags including the vaccine candidate MSP-1 (20 -22), are present in up to 25% of cord samples in sub-Saharan Africa. Plasmodial Ag-specific Th2-type responses have been recalled in cord blood mononuclear cell (CBMC) cultures (23).…”

Section: P Lasmodium Falciparum (Pf)mentioning

confidence: 99%

IFN-γ and IL-10 Mediate Parasite-Specific Immune Responses of Cord Blood Cells Induced by Pregnancy-Associated Plasmodium falciparum Malaria

Brustoski

Möller

Kramer

et al. 2005

The Journal of Immunology

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Available evidence suggests that immune cells from neonates born to mothers with placental Plasmodium falciparum (Pf) infection are sensitized to parasite Ag in utero but have reduced ability to generate protective Th1 responses. In this study, we detected Pf Ag-specific IFN-γ+ T cells in cord blood from human neonates whose mothers had received treatment for malaria or who had active placental Pf infection at delivery, with responses being significantly reduced in the latter group. Active placental malaria at delivery was also associated with reduced expression of monocyte MHC class I and II in vivo and following short term in vitro coculture with Pf Ag compared with levels seen in neonates whose mothers had received treatment during pregnancy. Given that APC activation and Th1 responses are driven in part by IFN-γ and down-regulated by IL-10, we examined the role of these cytokines in modulating the Pf Ag-specific immune responses in cord blood samples. Exogenous recombinant human IFN-γ and neutralizing anti-human IL-10 enhanced T cell IFN-γ production, whereas recombinant human IFN-γ also restored MHC class I and II expression on monocytes from cord blood mononuclear cells cocultured with Pf Ag. Accordingly, active placental malaria at delivery was associated with increased frequencies of Pf Ag-specific IL-10+CD4+ T cells in cord blood mononuclear cell cultures from these neonates. Generation and maintenance of IL-10+ T cells in utero may thus contribute to suppression of APC function and Pf Ag-induced Th1 responses in newborns born to mothers with placental malaria at delivery, which may increase susceptibility to infection later in life.

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Section: P Lasmodium Falciparum (Pf)mentioning

confidence: 99%

IFN-γ and IL-10 Mediate Parasite-Specific Immune Responses of Cord Blood Cells Induced by Pregnancy-Associated Plasmodium falciparum Malaria

Brustoski

Möller

Kramer

et al. 2005

The Journal of Immunology

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“…The presence of IgM or IgE Abs to malaria Ags in cord blood constitutes prima facie evidence of in utero sensitization since, unlike IgG, these Ig isotypes do not cross the placenta from the maternal circulation (8,11,12). There have been relatively fewer studies of cord blood T cell responses to malaria Ags (12)(13)(14) and to our knowledge, no descriptions of cord blood B cell responses. These investigations, which reported lymphocyte proliferation, IL-2, IL-4, and IFN-␥ responses to lysates of infected red cells (i.e., schizont extracts), recombinant proteins, or synthetic antigenic peptides, suggest that a small proportion of infants become sensitized to malaria Ags during gestation.…”

Section: P Regnancy Is Associated With An Increased Risk Of Maternalmentioning

confidence: 99%

“…These investigations, which reported lymphocyte proliferation, IL-2, IL-4, and IFN-␥ responses to lysates of infected red cells (i.e., schizont extracts), recombinant proteins, or synthetic antigenic peptides, suggest that a small proportion of infants become sensitized to malaria Ags during gestation. For example, Fievet et al (14) reported that 9.8% of 164 Cameroonian newborns had cord blood lymphocyte (CBL) 3 IFN-␥ responses to native P. falciparum ring-infected erythrocyte surface Ag (Pf155/RESA).…”

Section: P Regnancy Is Associated With An Increased Risk Of Maternalmentioning

confidence: 99%

Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

King

Malhotra

Wamachi

et al. 2002

The Journal of Immunology

104

108

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Infants born in areas of stable malaria transmission are relatively protected against severe morbidity and high density Plasmodium falciparum blood-stage infection. This protection may involve prenatal sensitization and immunologic reactivity to malaria surface ligands that participate in invasion of red cells. We examined cord blood T and B cell immunity to P. falciparum merozoite surface protein-1 (MSP-1) in infants born in an area of stable malaria transmission in Kenya. T cell cytokine responses to the C-terminal 19-kDa fragment of MSP-1 (MSP-119) were detected in 24 of 92 (26%) newborns (4–192 IFN-γ and 3–88 IL-4-secreting cells per 106/cord blood lymphocytes). Peptide epitopes in the N-terminal block 3 region of MSP-1 also drove IFN-γ and/or IL-13 production. There was no evidence of prenatal T cell sensitization to liver-stage Ag-1. A total of 5 of 86 (6%) newborns had cord blood anti-MSP-119 IgM Abs, an Ig isotype that does not cross the placenta and is therefore of fetal origin. The frequency of neonatal B cell sensitization was higher than that indicated by serology alone, as 5 of 27 (18%) cord blood samples contained B cells that produced IgG when stimulated with MSP-119 in vitro. Neonatal B cell IgG responses were restricted to the Q-KNG allele of MSP-119, the major variant in this endemic area, whereas T cells responded to all four MSP-119 alleles evaluated. In utero sensitization to MSP-1 correlated with the presence of malaria parasites in cord blood (χ2 = 20, p < 0.0001). These data indicate that prenatal sensitization to blood-stage Ags occurs in infants born in malaria endemic areas.

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“…These have demonstrated low level reactivity to schizont extract, and certain blood stage Ag, and lack of reactivity to liver stage Ag [7][8][9][10][11]. Healthy adults living in malaria endemic regions generally have low level cellular reactivity to P. falciparum Ag despite lifelong exposure to parasites [12][13][14].…”

Section: Introductionmentioning

confidence: 99%

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

et al. 2010

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Placental malaria (PM), a frequent infection of pregnancy, provides an ideal opportunity to investigate the impact on immune development of exposure of the foetal immune system to foreign Ag. We investigated the effect of PM on the regulatory phenotype and function of cord blood cells from healthy Gambian newborns and peripheral blood cells from their mothers, and analyzed for effects on the balance between regulatory and effector responses. Using the gold standard for classifying PM we further distinguished between resolved infection and acute or chronic PM active at the time of delivery. We show that exposure to malarial Ag in utero results in the expansion of malaria-specific FOXP31 Treg and more generalized FOXP3 1 CD4 1 Treg in chronic and resolved PM, alongside increased Th1 pro-inflammatory responses (IFN-c, TNF-a, IFN-c:IL-10) in resolved PM infection only. These observations demonstrate a clear effect of exposure to malarial Ag in foetal life on the immune environment at birth, with a regulatory response dominating in the newborns with ongoing chronic PM, while those with resolved infection produce both regulatory and inflammatory responses. The findings might explain some of the adverse effects on the health of babies born to women with PM.

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Malaria Cellular Immune Responses in Neonates From Cameroon

Cited by 65 publications

References 21 publications

IFN-γ and IL-10 Mediate Parasite-Specific Immune Responses of Cord Blood Cells Induced by Pregnancy-Associated Plasmodium falciparum Malaria

IFN-γ and IL-10 Mediate Parasite-Specific Immune Responses of Cord Blood Cells Induced by Pregnancy-Associated Plasmodium falciparum Malaria

Acquired Immune Responses to Plasmodium falciparum Merozoite Surface Protein-1 in the Human Fetus

The effect of placental malaria infection on cord blood and maternal immunoregulatory responses at birth

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