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Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life
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Background: Factors driving inter-individual differences in immune responses upon different types of prenatal malaria
exposure (PME) and subsequent risk of malaria in infancy remain poorly understood. In this study, we examined the
impact of four types of PME (i.e., maternal peripheral infection and placental acute, chronic, and past infections) on
both spontaneous and toll-like receptors (TLRs)-mediated cytokine production in cord blood and how these innate
immune responses modulate the risk of malaria during the first year of life.
Methods: We conducted a birth cohort study of 313 mother-child pairs nested within the COSMIC clinical trial
(NCT01941264), which was assessing malaria preventive interventions during pregnancy in Burkina Faso. Malaria
infections during pregnancy and infants’ clinical malaria episodes detected during the first year of life were recorded.
Supernatant concentrations of 30 cytokines, chemokines, and growth factors induced by stimulation of cord blood
with agonists of TLRs 3, 7/8, and 9 were measured by quantitative suspension array technology. Crude concentrations
and ratios of TLR-mediated cytokine responses relative to background control were analyzed.
Results: Spontaneous production of innate immune biomarkers was significantly reduced in cord blood of infants
exposed to malaria, with variation among PME groups, as compared to those from the non-exposed control group.
However, following TLR7/8 stimulation, which showed higher induction of cytokines/chemokines/growth factors than
TLRs 3 and 9, cord blood cells of infants with evidence of past placental malaria were hyper-responsive in comparison
to those of infants not-exposed. In addition, certain biomarkers, which levels were significantly modified depending on
the PME category, were independent predictors of either malaria risk (GM-CSF TLR7/8 crude) or protection (IL-12 TLR7/
8 ratio and IP-10 TLR3 crude, IL-1RA TLR7/8 ratio) during the first year of life.
Conclusions: These findings indicate that past placental malaria has a profound effect on fetal immune system and
that the differential alterations of innate immune responses by PME categories might drive heterogeneity between
individuals to clinical malaria susceptibility during the first year of life
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NATAMA, Hamtandi Magloire, et al. Modulation of innate immune responses at birth by prenatal
malaria exposure and association with malaria risk during the
first year of life. BMC medicine. 2018. Vol. 16, num. 198. ISSN 1741-7015. [consulted: 7 of October of 2026]. Available at: https://hdl.handle.net/2445/134501