Pregnancy-associated malaria affects toll-like receptor ligand-induced cytokine responses in cord blood.

Abstract

BACKGROUND: Pregnancy-associated malaria is known to modify fetal immunity. Most previous studies have been cross-sectional in nature and have focused on the priming of acquired immune responses in utero. In this context, the influence of the timing and/or duration of placental infection with Plasmodium falciparum are unknown, and changes to innate immune responses have not been studied extensively. METHODS: Pregnant women in Gabon, where P. falciparum infection is endemic, were followed up through monthly clinical and parasitological examinations from the second trimester to delivery. Cells of neonates born to mothers who had acquired P. falciparum infection <or=1 month before delivery had significantly altered interferon-gamma and tumor necrosis factor-alpha responses after stimulation with the Toll-like receptor (TLR) ligands lipopolysaccharide and polyinosine-polycytidylic acid, compared with cells of neonates born either to mothers free of P. falciparum infection or to mothers who were successfully treated for malaria during pregnancy. An independent association between parity and neonatal TLR responsiveness was also discerned in our study. CONCLUSION: P. falciparum infection history during pregnancy appears to have a pronounced effect on neonatal innate immune responses. The observed effects may have profound implications for the outcome of newly encountered infections in early life.