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Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport.
- Source :
-
PLoS pathogens [PLoS Pathog] 2013 Feb; Vol. 9 (2), pp. e1003153. Date of Electronic Publication: 2013 Feb 07. - Publication Year :
- 2013
-
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.
- Subjects :
- Adolescent
Adult
Amino Acid Transport System A genetics
Amino Acid Transport System A metabolism
Amino Acids analysis
Biological Transport
Case-Control Studies
Cell Line, Tumor
Cohort Studies
Female
Fetal Growth Retardation etiology
Fetal Growth Retardation immunology
Fetal Growth Retardation metabolism
Humans
Infant
Infant, Low Birth Weight
Infant, Newborn
Interleukin-1beta blood
Interleukin-1beta metabolism
Malaria, Falciparum complications
Malaria, Falciparum immunology
Malawi
Maternal-Fetal Exchange immunology
Monocytes
Placenta immunology
Placenta metabolism
Placenta Diseases immunology
Plasmodium falciparum physiology
Pregnancy
Pregnancy Complications, Parasitic immunology
Young Adult
Amino Acids metabolism
Malaria, Falciparum metabolism
Placenta Diseases metabolism
Plasmodium falciparum immunology
Pregnancy Complications, Parasitic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 9
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 23408887
- Full Text :
- https://doi.org/10.1371/journal.ppat.1003153