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Plasmodium knowlesi Cytoadhesion Involves SICA Variant Proteins.

Mariko S Peterson1,2, Chester J Joyner1,2,3, Stacey A Lapp1,2

  • 1Emory National Primate Research Center, Emory University, Atlanta, GA, United States.

Frontiers in Cellular and Infection Microbiology
|July 11, 2022
PubMed
Summary

Plasmodium knowlesi malaria parasites sequester in gastrointestinal tissues of rhesus monkeys, explaining human symptoms. This sequestration is linked to Schizont-Infected Cell Agglutination (SICA) antigens and spleen function.

Keywords:
Plasmodium falciparumanemiaantigenic variationgastritishistopathology (HPE)infected erythrocytesmalariarhesus monkey (Macaca mulatta)

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Area of Science:

  • Parasitology
  • Immunology
  • Pathology

Background:

  • Plasmodium knowlesi is a zoonotic parasite causing significant malaria cases in Southeast Asia, particularly Malaysia.
  • Rhesus monkeys (Macaca mulatta) serve as a model for studying severe malaria, chronicity, and antigenic variation in Plasmodium.
  • Schizont-Infected Cell Agglutination (SICA) antigens were first identified on Plasmodium-infected erythrocytes in rhesus monkeys and are crucial for antigenic variation.

Purpose of the Study:

  • To comprehensively analyze clinical parameters and infected red blood cell sequestration in Plasmodium knowlesi infections in rhesus monkeys.
  • To investigate the role of SICA antigens in parasite sequestration and its correlation with observed clinical symptoms.

Main Methods:

  • Longitudinal P. knowlesi infections were studied in rhesus monkeys.
  • Histopathological analysis of 22 tissue types was performed to assess parasite distribution and erythrocyte margination.
  • Comparative analysis was conducted between infected and splenectomized rhesus monkeys.

Main Results:

  • A significantly higher burden of Plasmodium knowlesi parasites was found in the gastrointestinal tissues of infected rhesus monkeys.
  • Extensive margination of infected erythrocytes along the endothelium was observed in gastrointestinal tissues, correlating with reported human symptoms.
  • Margination was absent in splenectomized rhesus monkeys infected with parasites lacking SICA protein expression.

Conclusions:

  • The study provides direct evidence that a subpopulation of P. knowlesi parasites cytoadheres and sequesters, likely mediated by SICA variant antigens.
  • SICA-mediated sequestration in the vasculature, particularly in the gastrointestinal tract, may explain the gastrointestinal symptoms in human P. knowlesi malaria.
  • This mechanism is analogous to the cytoadherence function of Erythrocyte Membrane Protein-1 in Plasmodium falciparum infections.