 | Hamtandi Magloire Natama, Gemma Moncunill, Eduard Rovira-Vallbona, Héctor Sanz, Hermann Sorgho, Ruth Aguilar, Maminata Coulibaly-Traoré, M Athanase Somé, Susana Scott, Innocent Valéa, Petra F Mens, Henk D F H Schallig, Luc Kestens, Halidou Tinto, Carlota Doba no, Anna Rosanas-Urgell Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life (Journal Article) In: BMC Med., vol. 16, no. 1, pp. 198, 2018, ISSN: 1741-7015. @article{Natama2018-es,
title = {Modulation of innate immune responses at birth by prenatal malaria exposure and association with malaria risk during the first year of life},
author = {Hamtandi Magloire Natama and Gemma Moncunill and Eduard Rovira-Vallbona and H\'{e}ctor Sanz and Hermann Sorgho and Ruth Aguilar and Maminata Coulibaly-Traor\'{e} and M Athanase Som\'{e} and Susana Scott and Innocent Val\'{e}a and Petra F Mens and Henk D F H Schallig and Luc Kestens and Halidou Tinto and Carlota Doba no and Anna Rosanas-Urgell},
doi = {10.1186/s12916-018-1187-3},
issn = {1741-7015},
year = {2018},
date = {2018-11-01},
urldate = {2018-11-01},
journal = {BMC Med.},
volume = {16},
number = {1},
pages = {198},
abstract = {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.},
keywords = {Cytokines; Innate immunity; Malaria in infancy; Malaria in pregnancy; Prenatal malaria exposure; Toll-like receptor},
pubstate = {published},
tppubtype = {article}
}
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. |
