Phong Zhi-Ying, Chin Joo-Yie, Ng Yee Ling, Zakaria Nurul Izza, Athirah-Azman Siti Nur, Kosaisavee Varakorn, Rénia Laurent, Lee Wenn-Chyau
Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Department of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia.
Front Cell Infect Microbiol. 2025 May 13;15:1599872. doi: 10.3389/fcimb.2025.1599872. eCollection 2025.
The pathogenesis of severe malaria is primarily attributed to the cytoadherence properties of -infected erythrocytes (IRBC), which include rosetting and IRBC-endothelial cytoadherence. These cytoadherence events are influenced by various parasite- and host-derived factors. Previously, antibodies against human periostin (OSF-2), an inflammation-associated protein, were reported to inhibit rosetting. In this study, we aimed to characterize the OSF-2-mediated cytoadherence in infections caused by (the most fatal human malaria parasite) and (an emerging, potentially fatal zoonotic malaria parasite).
Laboratory-adapted and isolates were cultured, and the late-stage parasites were purified for experiments using recombinant human OSF-2.
We found that OSF-2 at a concentration of 200 ng/ml induced rosette-stimulation in both parasite species. Furthermore, we demonstrated the serum dependency of OSF-2-mediated rosetting. The rosette-stimulating effect of OSF-2 was completely abolished when IRBC were treated with a low concentration of trypsin. This suggests a role for erythrocyte membrane protein 1 (PfEMP1) in OSF-2-mediated rosetting by , and reveals the trypsin-sensitive nature of the P. knowlesi-derived ligands involved in OSF-2-mediated rosetting. We also found that OSF-2-mediated rosetting was independent of the ABO blood group. Additionally, we demonstrated the ability of OSF-2 to disrupt the IRBC-endothelial binding.
This work contributes to our understanding of the host-parasite interactions in malaria pathobiology.
重症疟疾的发病机制主要归因于感染疟原虫的红细胞（IRBC）的细胞黏附特性，其中包括花结形成和IRBC与内皮细胞的黏附。这些细胞黏附事件受多种寄生虫和宿主来源的因素影响。此前，有报道称针对人骨膜蛋白（OSF-2）（一种炎症相关蛋白）的抗体可抑制花结形成。在本研究中，我们旨在表征OSF-2介导的细胞黏附在由恶性疟原虫（最致命的人类疟原虫）和诺氏疟原虫（一种新出现的、可能致命的人兽共患疟原虫）引起的感染中的情况。
培养实验室适应的恶性疟原虫和诺氏疟原虫分离株，并使用重组人OSF-2纯化晚期疟原虫用于实验。
我们发现浓度为200 ng/ml的OSF-2在两种疟原虫物种中均诱导花结刺激。此外，我们证明了OSF-2介导的花结形成对血清的依赖性。当IRBC用低浓度胰蛋白酶处理时，OSF-2的花结刺激作用完全消除。这表明恶性疟原虫红细胞膜蛋白1（PfEMP1）在OSF-2介导的恶性疟原虫花结形成中起作用，并揭示了参与OSF-2介导的花结形成的诺氏疟原虫来源配体的胰蛋白酶敏感性质。我们还发现OSF-2介导的花结形成与ABO血型无关。此外，我们证明了OSF-2破坏IRBC与内皮细胞结合的能力。
这项工作有助于我们理解疟疾病理生物学中的宿主-寄生虫相互作用。
