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Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum

BACKGROUND: Malaria during pregnancy is characterized by the sequestration of malaria-infected red blood cells (iRBC) in the intervillous spaces of the placenta, often accompanied by the infiltration of maternal mononuclear cells, causing substantial maternal and foetal/infant morbidity. The iRBC bi...

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Autores principales: Lucchi, Naomi W, Peterson, David S, Moore, Julie M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268702/
https://www.ncbi.nlm.nih.gov/pubmed/18312657
http://dx.doi.org/10.1186/1475-2875-7-42
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author Lucchi, Naomi W
Peterson, David S
Moore, Julie M
author_facet Lucchi, Naomi W
Peterson, David S
Moore, Julie M
author_sort Lucchi, Naomi W
collection PubMed
description BACKGROUND: Malaria during pregnancy is characterized by the sequestration of malaria-infected red blood cells (iRBC) in the intervillous spaces of the placenta, often accompanied by the infiltration of maternal mononuclear cells, causing substantial maternal and foetal/infant morbidity. The iRBC bind to receptors expressed by the syncytiotrophoblast (ST). How ST responds to this interaction remains poorly understood. Because it is known that ST is immunoactive and can respond to infectious agents, the consequences of this ST-iRBC interaction should be investigated. METHODS: An in vitro system was used to assess the biochemical and immunological changes induced in ST by ST-adherent iRBCs. Changes in ST mitogen-activated protein kinase (MAPK) activation were assessed by immunoblotting and mRNA expression levels of selected cytokine and chemokines in primary ST bound by iRBC were determined using real-time, reverse transcription PCR. In addition, secreted cytokine and chemokine proteins were assayed by standard ELISA, and chemotaxis of PBMC was assessed using a two-chamber assay system. RESULTS: Following iRBC/ST interaction, ST C-Jun N-terminal kinase 1 (JNK1) was activated and modest increases in the mRNA expression of TGF-β and IL-8/CXCL8 were observed. In addition, this interaction increased secretion of MIF and MIP-1α/CCL3 by ST and induced migration of PBMC towards iRBC-stimulated ST. CONCLUSION: Results from this study provide the first evidence that ST participates in shaping the local immunological milieu and in the recruitment of maternal immune cells to the maternal blood space during placental malaria infection.
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spelling pubmed-22687022008-03-18 Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum Lucchi, Naomi W Peterson, David S Moore, Julie M Malar J Research BACKGROUND: Malaria during pregnancy is characterized by the sequestration of malaria-infected red blood cells (iRBC) in the intervillous spaces of the placenta, often accompanied by the infiltration of maternal mononuclear cells, causing substantial maternal and foetal/infant morbidity. The iRBC bind to receptors expressed by the syncytiotrophoblast (ST). How ST responds to this interaction remains poorly understood. Because it is known that ST is immunoactive and can respond to infectious agents, the consequences of this ST-iRBC interaction should be investigated. METHODS: An in vitro system was used to assess the biochemical and immunological changes induced in ST by ST-adherent iRBCs. Changes in ST mitogen-activated protein kinase (MAPK) activation were assessed by immunoblotting and mRNA expression levels of selected cytokine and chemokines in primary ST bound by iRBC were determined using real-time, reverse transcription PCR. In addition, secreted cytokine and chemokine proteins were assayed by standard ELISA, and chemotaxis of PBMC was assessed using a two-chamber assay system. RESULTS: Following iRBC/ST interaction, ST C-Jun N-terminal kinase 1 (JNK1) was activated and modest increases in the mRNA expression of TGF-β and IL-8/CXCL8 were observed. In addition, this interaction increased secretion of MIF and MIP-1α/CCL3 by ST and induced migration of PBMC towards iRBC-stimulated ST. CONCLUSION: Results from this study provide the first evidence that ST participates in shaping the local immunological milieu and in the recruitment of maternal immune cells to the maternal blood space during placental malaria infection. BioMed Central 2008-02-29 /pmc/articles/PMC2268702/ /pubmed/18312657 http://dx.doi.org/10.1186/1475-2875-7-42 Text en Copyright © 2008 Lucchi et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Lucchi, Naomi W
Peterson, David S
Moore, Julie M
Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
title Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
title_full Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
title_fullStr Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
title_full_unstemmed Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
title_short Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum
title_sort immunologic activation of human syncytiotrophoblast by plasmodium falciparum
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2268702/
https://www.ncbi.nlm.nih.gov/pubmed/18312657
http://dx.doi.org/10.1186/1475-2875-7-42
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