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Published on: May 16, 2013
Infectivity of Plasmodium falciparum in Malaria-Naive Individuals Is Related to Knob Expression and Cytoadherence of
Danielle I Stanisic1, John Gerrard2, James Fink2
1Institute for Glycomics, Griffith University, Southport, Queensland, Australia.
Abstract:
Plasmodium falciparum is the most virulent human malaria parasite because of its ability to cytoadhere in the microvasculature. Nonhuman primate studies demonstrated relationships among knob expression, cytoadherence, and infectivity. This has not been examined in humans. Cultured clinical-grade P. falciparum parasites (NF54, 7G8, and 3D7B) and ex vivo-derived cell banks were characterized. Knob and knob-associated histidine-rich protein expression, CD36 adhesion, and antibody recognition of parasitized erythrocytes (PEs) were evaluated. Parasites from the cell banks were administered to malaria-naive human volunteers to explore infectivity. For the NF54 and 3D7B cell banks, blood was collected from the study participants for in vitro characterization. All parasites were infective in vivo However, infectivity of NF54 was dramatically reduced. In vitro characterization revealed that unlike other cell bank parasites, NF54 PEs lacked knobs and did not cytoadhere. Recognition of NF54 PEs by immune sera was observed, suggesting P. falciparum erythrocyte membrane protein 1 expression. Subsequent recovery of knob expression and CD36-mediated adhesion were observed in PEs derived from participants infected with NF54. Knobless cell bank parasites have a dramatic reduction in infectivity and the ability to adhere to CD36. Subsequent infection of malaria-naive volunteers restored knob expression and CD36-mediated cytoadherence, thereby showing that the human environment can modulate virulence.
Insights
Knobless Plasmodium falciparum parasites showed reduced infectivity and adhesion. However, infection in humans restored these virulence factors, demonstrating the human environment
Area of Science:
- Malariology
- Parasitology
- Human Infectious Diseases
Background:
- Plasmodium falciparum causes severe malaria due to cytoadherence in blood vessels.
- Knob expression, cytoadherence, and infectivity links are known in primates but unstudied in humans.
Purpose of the Study:
- To investigate the role of knob expression and CD36 cytoadherence in human Plasmodium falciparum infection and virulence.
- To determine if the human environment can restore virulence in knobless parasites.
Main Methods:
- Characterization of cultured P. falciparum parasites (NF54, 7G8, 3D7B) for knob expression, CD36 adhesion, and antibody recognition.
- Administration of parasites to malaria-naive human volunteers to assess infectivity.
- In vitro analysis of infected volunteers' blood to monitor parasite characteristics.
Main Results:
- All parasites were infective in vivo, but NF54 showed significantly reduced infectivity.
- NF54 parasites lacked knobs and CD36 cytoadherence in vitro, yet were recognized by immune sera.
- Infection with NF54 in volunteers restored knob expression and CD36-mediated cytoadherence.
Conclusions:
- Knobless P. falciparum exhibits reduced infectivity and adhesion.
- The human host environment can restore virulence factors like knob expression and cytoadherence in P. falciparum.
- This study highlights the dynamic interplay between parasite virulence and the human host.
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