title: Immunologic activation of human syncytiotrophoblast by Plasmodium falciparum.
abstract: 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-beta and IL-8/CXCL8 were observed. In addition, this interaction increased secretion of MIF and MIP-1alpha/CCL3 by ST and induced migration of PBMC towards iRBC-stimulated ST.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Infectious Diseases and Center for Tropical and Emerging Global Diseases, University of Georgia, Athens, GA 30602, USA. frd9@cdc.gov
authors.forename: Naomi W
authors.initials: NW
authors.lastname: Lucchi
authors.forename: David S
authors.initials: DS
authors.lastname: Peterson
authors.forename: Julie M
authors.initials: JM
authors.lastname: Moore
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002460:Cell Line; D054443:Cell Migration Assays; D002634:Chemotaxis, Leukocyte; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology; D004912:Erythrocytes / Q000469:parasitology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D010920:Placenta / Q000166:cytology / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014327:Trophoblasts / Q000276:immunology* / Q000469:parasitology*
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D048055:Mitogen-Activated Protein Kinase 8