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

Abstract

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.

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

“…+ FOXP3 + cells only after in vitro stimulation with merozoites or staphylococcal enterotoxin B in offspring of women with chronic or past but not active malaria (37). A third study found no association with placental malaria and T regs in cord blood (38), similar to the lack of association with malaria infection in women for the current study.…”

“…Alternatively, in utero exposure to malaria blood-stage Ags may trigger activation and expansion of regulatory T cells (T regs ) and/or increased production of immunomodulatory cytokines such as IL-10 or TGF-b (33)(34)(35). Recently, several studies have identified expanded populations of CD4 + T cells capable of producing IL-10 in cord blood from offspring of women with placental malaria when compared with those without placental malaria (36,37). In some of these studies, specifically CD4 + CD25 hi cells have been shown to be an important source of 38 (37).…”

“…Recently, several studies have identified expanded populations of CD4 + T cells capable of producing IL-10 in cord blood from offspring of women with placental malaria when compared with those without placental malaria (36,37). In some of these studies, specifically CD4 + CD25 hi cells have been shown to be an important source of 38 (37). These studies, however, failed to isolate and fully characterize these T regs .…”

Immune responses during gestational malaria: a review of the current knowledge and future trend of research

“…However, a deregulation of cytokine networks can lead to adverse pregnancy outcomes including spontaneous abortion, preterm labour, pre-eclampsia, and intrauterine growth restriction [76,77]. Such is the case of gestational malaria, in which a pro-inflammatory status has been confirmed and contributes to explain the deleterious effect of P. falciparum infection in mother and fetus [78].…”

Delaying Bacillus Calmette-Guérin Vaccination from Birth to 4 1/2 Months of Age Reduces Postvaccination Th1 and IL-17 Responses but Leads to Comparable Mycobacterial Responses at 9 Months of Age

“…Placental malaria was assessed in maternal placental biopsies by microscopy (50). Further venous blood samples of 1 ml/kg (maximum 5 ml) were collected at 4 1/2 and 9 mo of age and a TB questionnaire was completed to assess for TB exposure.…”