The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites

IntroductionThe 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. Prev...

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Main Authors: Zhi-Ying Phong, Joo-Yie Chin, Yee Ling Ng, Nurul Izza Zakaria, Siti Nur Athirah-Azman, Varakorn Kosaisavee, Laurent Rénia, Wenn-Chyau Lee
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-05-01
Series:Frontiers in Cellular and Infection Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fcimb.2025.1599872/full
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author Zhi-Ying Phong
Zhi-Ying Phong
Joo-Yie Chin
Yee Ling Ng
Nurul Izza Zakaria
Siti Nur Athirah-Azman
Siti Nur Athirah-Azman
Varakorn Kosaisavee
Laurent Rénia
Laurent Rénia
Laurent Rénia
Wenn-Chyau Lee
Wenn-Chyau Lee
author_facet Zhi-Ying Phong
Zhi-Ying Phong
Joo-Yie Chin
Yee Ling Ng
Nurul Izza Zakaria
Siti Nur Athirah-Azman
Siti Nur Athirah-Azman
Varakorn Kosaisavee
Laurent Rénia
Laurent Rénia
Laurent Rénia
Wenn-Chyau Lee
Wenn-Chyau Lee
author_sort Zhi-Ying Phong
collection DOAJ
description IntroductionThe 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).MethodsLaboratory-adapted P. falciparum and P. knowlesi isolates were cultured, and the late-stage parasites were purified for experiments using recombinant human OSF-2.ResultsWe 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.DiscussionThis work contributes to our understanding of the host-parasite interactions in malaria pathobiology.
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spelling doaj-art-5d622b78abfc4e3581529b77e386b1a32025-08-20T02:15:24ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882025-05-011510.3389/fcimb.2025.15998721599872The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasitesZhi-Ying Phong0Zhi-Ying Phong1Joo-Yie Chin2Yee Ling Ng3Nurul Izza Zakaria4Siti Nur Athirah-Azman5Siti Nur Athirah-Azman6Varakorn Kosaisavee7Laurent Rénia8Laurent Rénia9Laurent Rénia10Wenn-Chyau Lee11Wenn-Chyau Lee12Department of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, MalaysiaDepartment of Medical Microbiology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, MalaysiaDepartment of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, MalaysiaCollaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Bandar Puncak Alam, Selangor, MalaysiaDepartment of Pathology, Hospital Tengku Ampuan Afzan, Kuantan, Pahang, MalaysiaHigher Institution Centre of Excellence, Tropical Infectious Diseases Research and Education Centre (TIDREC), Universiti Malaya, Kuala Lumpur, MalaysiaInstitute for Advanced Studies, Universiti Malaya, Kuala Lumpur, MalaysiaDepartment of Parasitology and Entomology, Faculty of Public Health, Mahidol University, Bangkok, ThailandLee Kong Chian School of Medicine, Nanyang Technological University (NTU), Singapore, SingaporeSchool of Biological Sciences, Nanyang Technological University (NTU), Singapore, Singapore0A*STAR Infectious Diseases Labs, Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeDepartment of Parasitology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia0A*STAR Infectious Diseases Labs, Agency for Science, Technology and Research (A*STAR), Singapore, SingaporeIntroductionThe 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).MethodsLaboratory-adapted P. falciparum and P. knowlesi isolates were cultured, and the late-stage parasites were purified for experiments using recombinant human OSF-2.ResultsWe 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.DiscussionThis work contributes to our understanding of the host-parasite interactions in malaria pathobiology.https://www.frontiersin.org/articles/10.3389/fcimb.2025.1599872/fullPlasmodium falciparumPlasmodium knowlesiOSF-2endothelial bindingrosetting
spellingShingle Zhi-Ying Phong
Zhi-Ying Phong
Joo-Yie Chin
Yee Ling Ng
Nurul Izza Zakaria
Siti Nur Athirah-Azman
Siti Nur Athirah-Azman
Varakorn Kosaisavee
Laurent Rénia
Laurent Rénia
Laurent Rénia
Wenn-Chyau Lee
Wenn-Chyau Lee
The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites
Frontiers in Cellular and Infection Microbiology
Plasmodium falciparum
Plasmodium knowlesi
OSF-2
endothelial binding
rosetting
title The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites
title_full The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites
title_fullStr The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites
title_full_unstemmed The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites
title_short The role of periostin (OSF-2) in the cytoadherence phenomena mediated by malaria parasites
title_sort role of periostin osf 2 in the cytoadherence phenomena mediated by malaria parasites
topic Plasmodium falciparum
Plasmodium knowlesi
OSF-2
endothelial binding
rosetting
url https://www.frontiersin.org/articles/10.3389/fcimb.2025.1599872/full
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