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Plasmodium falciparum field isolates use complement receptor 1 (CR1) as a receptor for invasion of erythrocytes

Gordon A Awandare1, Carmenza Spadafora, J Kathleen Moch

  • 1Division of Malaria Vaccine Development, Walter Reed Army Institute of Research, Silver Spring, MD, United States.

Molecular and Biochemical Parasitology
|January 22, 2011
PubMed

Insights

Complement receptor 1 (CR1) mediates sialic acid-independent invasion of erythrocytes by Plasmodium falciparum field isolates. This finding is crucial for understanding malaria parasite invasion mechanisms and developing new interventions.

Area of Science:

  • Malariology
  • Infectious Diseases
  • Cellular and Molecular Biology

Background:

  • Plasmodium falciparum, the deadliest malaria parasite, typically invades human erythrocytes via sialic acid (SA)-dependent interactions with glycophorins.
  • Complement receptor 1 (CR1) has been identified as an SA-independent invasion receptor for laboratory strains of P. falciparum.
  • The role of CR1 in erythrocyte invasion by P. falciparum field isolates remains largely unexplored.

Purpose of the Study:

  • To investigate the role of CR1 in mediating erythrocyte invasion by P. falciparum field isolates from Kenya.
  • To determine if CR1-mediated invasion is sialic acid-independent in naturally acquired parasite strains.

Main Methods:

  • Erythrocyte invasion assays were performed using eight P. falciparum field isolates from Kenyan children.
  • Parasite invasion was assessed using neuraminidase-treated erythrocytes to remove sialic acid.
  • The effects of anti-CR1 antibodies and soluble CR1 (sCR1) on parasite invasion were evaluated.
  • Sequencing of the P. falciparum apical membrane antigen-1 (AMA-1) hypervariable region was conducted.

Main Results:

  • All tested field isolates demonstrated SA-independent erythrocyte invasion.
  • Invasion of neuraminidase-treated erythrocytes was significantly inhibited by anti-CR1 and sCR1.
  • Anti-CR1 and sCR1 partially blocked invasion of intact erythrocytes in most isolates.
  • Significant diversity was observed in the AMA-1 hypervariable region among the isolates.

Conclusions:

  • Complement receptor 1 (CR1) plays a significant role in mediating sialic acid-independent erythrocyte invasion by Plasmodium falciparum field isolates.
  • These findings highlight the importance of CR1 as an alternative invasion pathway for P. falciparum, particularly in natural settings.
  • The study underscores the potential of targeting CR1 for malaria intervention strategies.

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