TY - JOUR
T1 - Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life
AU - Natama, Hamtandi Magloire
AU - Moncunill, Gemma
AU - Rovira-Vallbona, Eduard
AU - Sanz, Hector
AU - Sorgho, Hermann
AU - Aguilar, Ruth
AU - Coulibaly-Traore, Maminata
AU - Some, M. Athanase
AU - Scott, Susana
AU - Valea, Innocent
AU - Mens, Petra F.
AU - Schallig, Henk D. F. H.
AU - Kestens, Luc
AU - Tinto, Halidou
AU - Dobano, Carlota
AU - Rosanas-Urgell, Anna
N1 - FTX; DOAJ
PY - 2018
Y1 - 2018
N2 - BackgroundFactors 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.MethodsWe 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.ResultsSpontaneous 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.ConclusionsThese 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.
AB - BackgroundFactors 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.MethodsWe 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.ResultsSpontaneous 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.ConclusionsThese 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.
KW - Malaria in pregnancy
KW - Prenatal malaria exposure
KW - Innate immunity
KW - Cytokines
KW - Toll-like receptor
KW - Malaria in infancy
KW - PLASMODIUM-FALCIPARUM MALARIA
KW - MEROZOITE SURFACE PROTEIN-1
KW - CORD BLOOD
KW - CYTOKINE RESPONSES
KW - PLACENTAL MALARIA
KW - NITRIC-OXIDE
KW - TNF-ALPHA
KW - IN-UTERO
KW - PROINFLAMMATORY CYTOKINES
KW - TRAINED IMMUNITY
U2 - 10.1186/s12916-018-1187-3
DO - 10.1186/s12916-018-1187-3
M3 - A1: Web of Science-article
SN - 1741-7015
VL - 16
JO - BMC Medicine
JF - BMC Medicine
M1 - 198
ER -