Phong Z.Y.Chin J.Y.Ng Y.L.Zakaria N.I.Athirah-Azman S.N.Kosaisavee V.Rénia L.Lee W.C.Mahidol University2025-06-052025-06-052025-01-01Frontiers in Cellular and Infection Microbiology Vol.15 (2025)https://repository.li.mahidol.ac.th/handle/123456789/110465Introduction: The pathogenesis of severe malaria is primarily attributed to the cytoadherence properties of Plasmodium-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 Plasmodium falciparum (the most fatal human malaria parasite) and P. knowlesi (an emerging, potentially fatal zoonotic malaria parasite). Methods: Laboratory-adapted P. falciparum and P. knowlesi isolates were cultured, and the late-stage parasites were purified for experiments using recombinant human OSF-2. Results: 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 P. falciparum erythrocyte membrane protein 1 (PfEMP1) in OSF-2-mediated rosetting by P. falciparum, 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. Discussion: This work contributes to our understanding of the host-parasite interactions in malaria pathobiology.MedicineImmunology and MicrobiologyArticleSCOPUS10.3389/fcimb.2025.15998722-s2.0-10500647137422352988