Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport.
Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplace...
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doaj-231202bd16b44597a9ea018b7a7012782020-11-25T00:43:35ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742013-02-0192e100315310.1371/journal.ppat.1003153Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport.Philippe BoeufElizabeth H AitkenUpeksha ChandrasiriCaroline Lin Lin ChuaBernie McInerneyLeon McQuadeMichael DuffyMalcolm MolyneuxGraham BrownJocelyn GlazierStephen J RogersonPlacental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na⁺-dependent ¹⁴C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM.http://europepmc.org/articles/PMC3567154?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Philippe Boeuf Elizabeth H Aitken Upeksha Chandrasiri Caroline Lin Lin Chua Bernie McInerney Leon McQuade Michael Duffy Malcolm Molyneux Graham Brown Jocelyn Glazier Stephen J Rogerson |
spellingShingle |
Philippe Boeuf Elizabeth H Aitken Upeksha Chandrasiri Caroline Lin Lin Chua Bernie McInerney Leon McQuade Michael Duffy Malcolm Molyneux Graham Brown Jocelyn Glazier Stephen J Rogerson Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. PLoS Pathogens |
author_facet |
Philippe Boeuf Elizabeth H Aitken Upeksha Chandrasiri Caroline Lin Lin Chua Bernie McInerney Leon McQuade Michael Duffy Malcolm Molyneux Graham Brown Jocelyn Glazier Stephen J Rogerson |
author_sort |
Philippe Boeuf |
title |
Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. |
title_short |
Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. |
title_full |
Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. |
title_fullStr |
Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. |
title_full_unstemmed |
Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. |
title_sort |
plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Pathogens |
issn |
1553-7366 1553-7374 |
publishDate |
2013-02-01 |
description |
Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na⁺-dependent ¹⁴C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM. |
url |
http://europepmc.org/articles/PMC3567154?pdf=render |
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