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Plasmodium falciparum Malaria Elicits Inflammatory Responses that Dysregulate Placental Amino Acid Transport

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Boeuf, Philippe, Aitken, Elizabeth H., Chandrasiri, Upeksha, Chua, Caroline Lin Lin, McInerney, Bernie, McQuade, Leon, Duffy, Michael, Molyneux, Malcolm E, Brown, Graham, Glazier, Jocelyn and Rogerson, Stephen J. (2013) 'Plasmodium falciparum Malaria Elicits Inflammatory Responses that Dysregulate Placental Amino Acid Transport'. PLoS Pathogens, Vol 9, Issue 2, e1003153.

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Abstract

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.

Item Type: Article
Subjects: QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58 Nucleic acids and derivatives (General)
QX Parasitology > Protozoa > QX 135 Plasmodia
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 750 Malaria
WQ Obstetrics > Pregnancy > WQ 200 General works
WS Pediatrics > By Age Groups > WS 420 Newborn infants. Neonatology
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.ppat.1003153
Depositing User: Lynn Roberts-Maloney
Date Deposited: 13 Feb 2015 11:25
Last Modified: 06 Feb 2018 13:08
URI: https://archive.lstmed.ac.uk/id/eprint/4900

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