Abstract
Plasmodium knowlesi is responsible for zoonotic malaria infections that are potentially fatal. While the severe pathology of falciparum malaria is associated with cytoadherence phenomena by Plasmodium falciparum-infected erythrocytes (IRBC), information regarding cytoadherence properties of P. knowlesi-IRBC remained scarce. Here, we characterized the cytoadherence properties of RBC infected with the laboratory-adapted P. knowlesi A1-H.1 strain. We found that late-stage IRBC formed rosettes in a human serum-dependent manner, and rosettes hampered IRBC phagocytosis. IRBC did not adhere much to unexposed (unstimulated) human endothelial cell lines derived from the brain (hCMEC/D3), lungs (HPMEC), and kidneys (HRGEC). However, after being “primed” with P. knowlesi culture supernatant, the IRBC-endothelial cytoadherence rate increased in HPMEC and HRGEC, but not in hCMEC/D3 cells. Both endothelial cytoadherence and rosetting phenomena were abrogated by treatment of P. knowlesi-IRBC with trypsin. We also found that different receptors were involved in IRBC cytoadherence to different types of endothelial cells. Although some of the host receptors were shared by both P. falciparum- and P. knowlesi-IRBC, the availability of glycoconjugates on the receptors might influence the capacity of P. knowlesi-IRBC to cytoadhere to these receptors.
Highlights
Malaria is still one of the significant healthcare burdens in many tropical and subtropical countries
No rosettes were found after the IRBCs were treated with 1 mg/ml of trypsin
Phagocytosis of IRBC by THP-1 cells (Figure 1E) was less efficient when parasites were grown in human AB serum-enriched media, which facilitated rosette formation (Figure 1F)
Summary
Malaria is still one of the significant healthcare burdens in many tropical and subtropical countries. Our current understandings on severe malaria pathogenesis are mostly based on the in-depth studies conducted on Plasmodium falciparum, the most fatal human malaria parasite. The severe pathogenesis in falciparum malaria is thought to be associated with the ability of P. falciparum-infected erythrocytes (IRBC) to stably adhere to endothelial cells (a phenomenon known as IRBC–endothelial cytoadherence) and uninfected erythrocytes (URBC) (a phenomenon called rosetting) (Craig et al, 2012; Lee et al, 2019). These phenomena disrupt blood flow and activate the endothelial cells, resulting in vascular leakage and injury, which are the hallmarks of severe malaria pathology. We characterized the cytoadherence properties of P. knowlesi A1-H.1, the reference strain that can be propagated in vitro with human RBC (Moon et al, 2013)
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