Plasmodium falciparum adhesion on human brain microvascular endothelial cells involves transmigration-like cup

Ronan Jambou1, Valery Combes, Marie-Jose Jambou

  • 1Vascular Immunology Unit, Department of Pathology and Bosch Institute, Sydney Medical School, The University of Sydney, New South Wales, Australia. rjambou@pasteur.fr

Plos Pathogens
|August 6, 2010
PubMed

Insights

In cerebral malaria, infected red blood cells transfer material to brain endothelial cells, altering their function and contributing to disease. This interaction opens intercellular junctions, making endothelial cells targets for immune responses.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Cerebral malaria is a lethal complication of malaria, marked by infected red blood cell sequestration in brain microvessels.
  • While IRBC adhesion molecules are known, the IRBC/EC junction structure and EC impact remain unclear.

Purpose of the Study:

  • To investigate the structural and functional consequences of infected red blood cell (IRBC) and brain endothelial cell (EC) interactions.
  • To elucidate the mechanisms underlying EC alterations in cerebral malaria.

Main Methods:

  • Co-culture of human brain microvascular EC monolayers with IRBC.
  • Analysis of material transfer, antigen uptake, and intercellular junction dynamics.

Main Results:

  • Demonstrated a trogocytosis-like transfer of IRBC material to ECs.
  • Observed TNF-enhanced IRBC engulfment and parasite antigen transfer to EC endosomes.
  • Showed cytoskeleton-dependent antigen transfer and opening of intercellular EC junctions.

Conclusions:

  • IRBC antigen transfer transforms ECs into immune targets, contributing to cerebral malaria pathology.
  • Adhesion-induced EC alterations, including junction opening and potential edema, are key features of severe malaria.

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