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Updated: Jun 5, 2025

In Vivo Assessment of Rodent Plasmodium Parasitemia and Merozoite Invasion by Flow Cytometry
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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
PubMed

Insights

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.
Keywords:
Biological sciencesMicrobiology parasiteMolecular microbiology

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