Fetal Immune Responses to Plasmodium falciparum Antigens in a Malaria-Endemic Region of Cameroon

Abstract

Plasmodium falciparum infection during pregnancy can lead to the transplacental passage of malarial Ags that are capable of inducing acquired immune responses in the fetus. Studies have identified cytokines produced by malaria-specific cord blood (CB) T cells, but information on fetal B cells is limited. Thus, CB mononuclear cells from 120 Cameroonian newborns were cultured for 7 days in vitro and supernatants were assessed by ELISA for Abs to an extract of malarial schizonts (MA), recombinant apical merozoite Ag 1 (AMA-1), the 42-kDa C-terminal region of merozoite surface protein 1 (MSP-142), a B epitope of ring-infected erythrocyte surface Ag (RESA), and the dominant B epitope of the circumsporozoite protein (CSP). Only 12% of supernatants contained IgM to MA but 78% had IgG to one or more malarial Ags, with 53% having IgG to AMA-1, 38% to MSP-142, 3% to RESA, and 0% to CSP. The Abs to AMA-1 and MSP-142 were predominantly IgG1 and IgG3. CB mononuclear cells were also tested for the ability to secrete cytokines in response to MA and a pool of conserved MSP-1 T cell epitopes. Among the Ag-reactive samples, 39.3% produced only Th2-type cytokines, whereas 60.6% produced a combination of Th1- and Th2-type cytokines. Although a Th2 bias was observed, the in utero cytokine environment was adequate to support isotype switching to cytophilic IgGs, the isotypes that are protective in adults. Because many infants living in a low transmission area are born with malaria-specific B and T cells, the influence of in utero priming on neonatal immunity merits further investigation.

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

“…This suppression is much more potent for Th1 than for Th2-type cytokine production by cord blood cells, consistent with generally Th2 cytokine bias of cord blood lymphocytes (18,63,64). IL-10 or TGF-b do not mediate this T reg suppression, consistent with some but not all prior studies (36,38).…”

“…The accumulation of infected erythrocytes in the placenta may result in transplacental transport of infected erythrocytes or their soluble components, thereby exposing and sensitizing the fetal immune system to P. falciparum Ags (8)(9)(10)(11)(12). The reported frequency of malaria bloodstage-specific T and B cell responses in cord blood mononuclear cells (CBMC) ranges from ∼5% to .70% (13)(14)(15)(16)(17)(18). The consequences of this prenatal exposure of the infant to P. falciparum remain poorly understood.…”

Evaluation of oxidative stress and antioxidant status of pregnant women suffering from malaria in Cameroon

“…Pregnant women experience lowered immunity to malaria. Malaria suppresses responses to immunogens, and placental malaria impairs materno-fetal antibody transfer, which potentially reduces the benefits of maternal immunization strategies (9)(10)(11). This is particularly frequent and severe in primigravidae (10,11).…”

“…Malaria suppresses responses to immunogens, and placental malaria impairs materno-fetal antibody transfer, which potentially reduces the benefits of maternal immunization strategies (9)(10)(11). This is particularly frequent and severe in primigravidae (10,11). Also, parasites-infected red blood cells (IRBCs) sequestration in the placenta is a key feature of infection by P. falciparum during pregnancy and is frequently associated with severe adverse outcomes for both mother and baby such as spontaneous abortion, preterm delivery, low birth weight and infant death, as well as severe anemia for both mother and infant (12)(13)(14).…”

Fine Specificity of Neonatal Lymphocytes to an Abundant Malaria Blood-Stage Antigen: Epitope Mapping ofPlasmodium falciparumMSP133

“…Notable infections that reproducibly stimulate an immune response in the fetus are HIV and CMV, and the parasitic infections Trypanosoma cruzi, toxoplasmosis, and malaria (1)(2)(3)(4)(5)(6). This prenatal priming has generated considerable interest because of the impact it might have on the infant.…”