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Updated: Jun 15, 2026
Selection of Plasmodium falciparum Parasites for Cytoadhesion to Human Brain Endothelial Cells
Published on: January 3, 2012
Plasmodium falciparum-infected erythrocyte co-culture with the monocyte cell line THP-1 does not trigger production
Janet Storm1, Grazia Camarda1, Michael J Haley2
1Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool, United Kingdom.
Abstract:
Monocytes contribute to the pro-inflammatory immune response during the blood stage of a Plasmodium falciparum infection, but their precise role in malaria pathology is not clear. Besides phagocytosis, monocytes are activated by products from P. falciparum infected erythrocytes (IE) and one of the activation pathways is potentially the NLR family pyrin domain containing 3 (NLRP3) inflammasome, a multi-protein complex that leads to the production of interleukin (IL)-1β. In cerebral malaria cases, monocytes accumulate at IE sequestration sites in the brain microvascular and the locally produced IL-1β, or other secreted molecules, could contribute to leakage of the blood-brain barrier. To study the activation of monocytes by IE within the brain microvasculature in an in vitro model, we co-cultured IT4var14 IE and the monocyte cell line THP-1 for 24 hours and determined whether generated soluble molecules affect barrier function of human brain microvascular endothelial cells, measured by real time trans-endothelial electrical resistance. The medium produced after co-culture did not affect endothelial barrier function and similarly no effect was measured after inducing oxidative stress by adding xanthine oxidase to the co-culture. While IL-1β does decrease barrier function, barely any IL-1β was produced in the co- cultures, indicative of a lack of or incomplete THP-1 activation by IE in this co-culture model.
Insights
Monocytes and malaria parasites (Plasmodium falciparum) do not activate inflammatory pathways in brain cells in this model. This suggests incomplete monocyte activation, potentially limiting their role in cerebral malaria pathology.
Area of Science:
- Immunology
- Infectious Diseases
- Neuroscience
Background:
- Monocytes are key immune cells in Plasmodium falciparum malaria, contributing to inflammation.
- The NLR family pyrin domain containing 3 (NLRP3) inflammasome pathway in monocytes may drive malaria pathology, particularly in cerebral malaria.
- Interleukin (IL)-1β, a product of NLRP3 inflammasome activation, is implicated in blood-brain barrier dysfunction.
Purpose of the Study:
- To investigate the activation of monocytes by Plasmodium falciparum infected erythrocytes (IE) in an in vitro model.
- To determine if soluble factors produced during monocyte-IE co-culture impact human brain microvascular endothelial cell barrier function.
Main Methods:
- Co-culture of IT4var14 IE with the THP-1 monocyte cell line for 24 hours.
- Measurement of endothelial barrier function using real-time trans-endothelial electrical resistance.
- Assessment of IL-1β production in co-culture supernatants.
Main Results:
- Co-culture medium did not alter endothelial barrier function.
- Oxidative stress induction did not enhance monocyte activation or affect barrier function.
- Minimal IL-1β production was observed, indicating limited THP-1 activation by IE.
Conclusions:
- In this in vitro model, Plasmodium falciparum infected erythrocytes do not fully activate monocytes via the NLRP3 inflammasome pathway.
- The limited IL-1β production suggests that monocyte-derived inflammatory mediators may not significantly contribute to blood-brain barrier leakage in this specific model of cerebral malaria.
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