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Updated: Jun 5, 2025
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In Vivo Assessment of Rodent Plasmodium Parasitemia and Merozoite Invasion by Flow Cytometry
Published on: April 5, 2015
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Red blood cell signaling is functionally conserved in Plasmodium invasion
James Jia Ming Yong1, Xiaohong Gao1, Prem Prakash1
1School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
Iscience
|December 5, 2024
Summary
Plasmodium merozoite invasion relies on a conserved host cell signaling pathway. RH5-basigin interaction triggers calcium influx, crucial for parasite entry and potentially targetable for new therapies.
Area of Science:
- Malariology
- Cellular Signaling
- Infectious Diseases
Background:
- Plasmodium merozoites interact with red blood cell (RBC) receptors during invasion.
- The role of RBC signaling in facilitating parasite entry remains unclear.
- Plasmodium falciparum is known to manipulate RBC calcium (Ca2+) signaling.
Purpose of the Study:
- To investigate the conserved role of RBC Ca2+ influx in Plasmodium invasion across species.
- To elucidate the signaling pathways triggered by merozoite ligand-receptor interactions.
- To identify potential therapeutic targets for blocking parasite invasion.
Main Methods:
- Investigated the role of RBC Ca2+ influx in invasion using various Plasmodium species.
- Examined the effect of RH5-basigin interaction on RBC signaling pathways.
- Utilized inhibitors to block RBC signaling pathways during invasion.
- Analyzed changes in RBC membrane protein complex association.
Main Results:
- Demonstrated a conserved requirement for RBC Ca2+ influx in Plasmodium invasion.
- Showed that RH5-basigin interaction triggers an increase in RBC cyclic adenosine monophosphate (cAMP).
- Confirmed that cAMP increase promotes Ca2+ influx, essential for invasion.
- Identified that RH5-basigin binding induces a multimeric RBC membrane complex involving the β-adrenergic receptor.
- Inhibitors targeting these RBC signaling pathways blocked Plasmodium invasion.
Conclusions:
- A conserved host cAMP-Ca2+ signaling cascade is essential for Plasmodium invasion.
- This signaling pathway is triggered by RH5-basigin interaction and involves RBC membrane complex reorganization.
- Targeting this conserved host signaling pathway offers a promising therapeutic strategy against malaria.
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