Plasmodium falciparum exposure in utero, maternal age and parity influence the innate activation of foetal antigen presenting cells

Abstract

BackgroundMalaria in pregnancy is associated with immunological abnormalities in the newborns, such as hampered T-helper 1 responses and increased T-regulatory responses, while the effect of maternal Plasmodium falciparum infection on foetal innate immunity is still controversial.Materials and methodsThe immunophenotype and cytokine release by dendritic cells (DC) and monocytes were evaluated in cord blood from 59 Beninese women with or without malaria infection by using flow cytometry.ResultsAccumulation of malaria pigment in placenta was associated with a partial maturation of cord blood myeloid and plasmacytoid DC, as reflected by an up-regulated expression of the major histocompatibility complex class II molecules, but not CD86 molecules. Cells of newborns of mothers with malaria pigment in their placenta also exhibited significantly increased cytokine responses upon TLR9 stimulation. In addition, maternal age and parity influenced the absolute numbers and activation status of cord blood antigen-presenting cells. Lastly, maternal age, but not parity, influenced TLR3, 4 and 9 responses in cord blood cells.DiscussionOur findings support the view that placental parasitization, as indicated by the presence of malaria pigment in placental leukocytes, is significantly associated with partial maturation of different DC subsets and also to slightly increased responses to TLR9 ligand in cord blood. Additionally, other factors, such as maternal age and parity should be taken into consideration when analysing foetal/neonatal innate immune responses.ConclusionThese data advocate a possible mechanism by which PAM may modulate foetal/neonatal innate immunity.

Neonatal antigen-presenting cells are functionally more quiescent in children born under traditional compared with modern environmental conditions

“…Interestingly, HLA-DR expression of APCs was reported to correlate with infection status, 31 including in neonates exposed to malaria prenatally. 32 Furthermore, enhanced baseline expression of the inhibitory markers ILT3 and ILT4 on monocytes of PNG neonates might also suggest enhanced potential for tolerogenic activity. PNG ILT3 1 ILT4 1 monocytes coexpressed high levels of HLA-DR, suggesting that cells with potential inhibitory function were those that had been activated in utero.…”

Malaria Modifies Neonatal and Early-Life Toll-Like Receptor Cytokine Responses

“…The choice of stimulants reflects a desire, based on our own knowledge and experience (32), to focus as much as possible on DC-mediated activity.…”

“…In the context of pregnancy, we and others have shown that placental infection with P. falciparum at delivery is associated with altered fetal innate immune responses, modified frequency of cord blood DC (31), partial activation of cord blood APC (32), and modulated cord blood cytokine responses to TLR ligation (33). Two independent studies in nonpregnant individuals have reported the capacity of P. falciparum infection to cause proinflammatory priming of responses to subsequent TLR ligation, a capacity that distinguishes the parasite from most other microbial pathogens (34,35).…”

High Seroprevalence of Chikungunya Virus Antibodies Among Pregnant Women Living in an Urban Area in Benin, West Africa

“…18 For this study, 352 pregnant women were enrolled at delivery after informed consent was obtained from July of 2006 to January of 2007 from the Hospital Mother and Child Lagune, the main obstetrical referring hospital in Cotonou, Benin and the Houenoussou Health Center in Cotonou, Benin. Women who underwent delivery at the above-mentioned clinics between July of 2006 and January of 2007 were enrolled in the study, regardless of presence or absence of fever or other symptoms.…”