Impaired placental autophagy in placental malaria

Dimasuay, Kris Genelyn, Gong, Lan, Rosario, Fredrick, McBryde, Emma, Spelman, Tim, Glazier, Jocelyn, Rogerson, Stephen J., Beeson, James G., Jansson, Thomas, Devenish, Rodney J., and Boeuf, Philippe (2017) Impaired placental autophagy in placental malaria. PLoS ONE, 12 (11). e0187291.

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Abstract

Background: Placental malaria is a major cause of low birthweight, principally due to impaired fetal growth. Intervillositis, a local inflammatory response to placental malaria, is central to the pathogenesis of poor fetal growth as it impairs transplacental amino acid transport. Given the link between inflammation and autophagy, we investigated whether placental malaria-associated intervillositis increased placental autophagy as a potential mechanism in impaired fetal growth.

Methods: We examined placental biopsies collected after delivery from uninfected women (n = 17) and from women with Plasmodium falciparum infection with (n = 14) and without (n = 7) intervillositis. Western blotting and immunofluorescence staining coupled with advanced image analysis were used to quantify the expression of autophagic markers (LC3-II, LC3-I, Rab7, ATG4B and p62) and the density of autophagosomes (LC3-positive puncta) and lysosomes (LAMP1-positive puncta).

Results: Placental malaria with intervillositis was associated with higher LC3-II: LC3-I ratio, suggesting increased autophagosome formation. We found higher density of autophagosomes and lysosomes in the syncytiotrophoblast of malaria-infected placentas with intervillositis. However, there appear to be no biologically relevant increase in LC3B/LAMP1 colocalization and expression of Rab7, a molecule involved in autophagosome/lysosome fusion, was lower in placental malaria with intervillositis, indicating a block in the later stage of autophagy. ATG4B and p62 expression showed no significant difference across histological groups suggesting normal autophagosome maturation and loading of cargo proteins into autophagosomes. The density of autophagosomes and lysosomes in the syncytiotrophoblast was negatively correlated with placental amino acid uptake.

Conclusions: Placental malaria-associated intervillositis is associated with dysregulated autophagy that may impair transplacental amino acid transport, possibly contributing to poor fetal growth.

Item ID: 51686
Item Type: Article (Research - C1)
ISSN: 1932-6203
Additional Information:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funders: University of Melbourne (UM), National Institutes of Health (NIH), National Health and Medical Research Council (NHMRC)
Projects and Grants: UM Henry and Rachael Ackman Travelling Scholarship, NIH RHD68370, NHMRC program grant 1092789
Date Deposited: 29 Nov 2017 07:43
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1108 Medical Microbiology > 110801 Medical Bacteriology @ 100%
SEO Codes: 92 HEALTH > 9204 Public Health (excl. Specific Population Health) > 920404 Disease Distribution and Transmission (incl. Surveillance and Response) @ 100%
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