The objective of this thesis was to investigate the immunological consequences of pregnancy associated malaria (PAM) in pregnant women and their newborns. The study populations comprise sub-groups drawn from a longitudinal study known as “Strategies TO Prevent Pregnancy Associated Malaria” (STOPPAM) that was conducted in parallel in the two study sites i.e. Benin and Tanzania. The STOPPAM objectives were to elucidate the mechanisms and course of PAM and quantify the effects of PAM on mothers and their childhood’s health. First, we characterized cell mediated-immunity from P. falciparum-infected or non-infected pregnant women. Two studies were carried out in two sub-groups of pregnant women at early pregnancy and at delivery. In the first study, we observed a decrease frequency of T cells independently of malaria infection in the twenty-four pregnant women matched at early pregnancy and at delivery. In the second study, we characterized: i) the frequency and the level of activation of cell mediated-immunity and ii) quantify the plasma level of cytokine and chemokine in sub-groups at early pregnancy and at delivery. We observed that malaria infected pregnant women enhanced qualitative and quantitative changes in cells frequencies early during pregnancy and at delivery. The main finding of this study was the B cells activation at any time of infection and the decreased frequency of Treg at early pregnancy. PAM enhanced also higher levels of IL-10, IP-10 and MIG in our sub-groups. These bio-markers were identified as risk factors of placental infection at delivery. These observations suggest the management of malaria control in pregnant women in early pregnancy. The second part of this thesis was focused on the impact of PAM on neonatal innate immune responses. In a first study, we characterized antigen-presenting cells (APC) in cord blood as a function of placental malaria infection or inflammation of the placenta. Our results showed that the presence of malaria pigment in the placenta was associated to partial activation of cord blooddendritic cells. Our results highlight the importance of the age of the mother at the time of pregnancy and parity on APC activation in cord blood. These results suggest that PAM can induce neonatal innate responses alteration. Then we considered the cytokine responses in cord blood and in peripheral blood of newborn, to TLR ligands in a cohort of 134 children. The observations from this study demonstrate that infection occurred close to/at delivery in the mother can induce modulation of young-children innate immune system, through the TLR. Our results suggest that susceptibility to malaria infection during the first year of life could depend on the period of stimulation of TLRs neonatal immune system. All the work done in this thesis provides an understanding of the cellular mechanisms involved in inflammatory and gestational malaria in pregnant women and in children. Our results have identified biomarkers associated with PAG.
Malaria associated with pregnancy : Immunological consequences in pregnant women and newborn