Work

IGFBP7 induces phenotypic shift from platelet-mediated autoagglutination to rosetting of Plasmodium knowlesi -infected erythrocytes

Year: 2026

Type: article

Abstract: Zoonotic malaria caused by Plasmodium knowlesi is an emerging infectious disease with persistent transmission in Southeast Asia over the past two decades. This zoonosis causes potentially life-threatening hematological complications such as thrombocytopenia. While mechanisms behind the malaria-induced acute thrombocytopenia remain to be fully deciphered, it is believed to be associated with the cytoadherence of Plasmodium-infected erythrocytes (IRBC) to platelets. Of note, platelet-mediated cytoadherence of IRBC gives rise to platelet-mediated clumping of IRBC, also known as IRBC autoagglutination. Nevertheless, most of the autoagglutination studies were performed with P. falciparum. In this study, we characterized autoagglutination of P. knowlesi and P. falciparum, and investigated the relationship between IRBC autoagglutination and rosetting rates (another IRBC cytoadherence phenomenon). Autoagglutination was found to be dependent on the presence of human serum and platelets, where the presence of platelets favored IRBC autoagglutination over rosetting. The autoagglutination of P. knowlesi and P. falciparum was mediated by CD36, where antibody blockade of CD36 inhibited autoagglutination and drove the IRBC to form more rosettes with the uninfected erythrocytes (URBC). Antibody blocking of P-selectin reduced only the autoagglutination of P. falciparum with no effect on the rosetting rates. Notably, the presence of IGFBP7 (a human-derived protein that facilitates the formation of type II rosettes) suppressed autoagglutination while stimulating rosetting rates of IRBC. Given the ability of IGFBP7 to alter the Plasmodium-mediated cytoadherence dynamics between autoagglutination and rosetting, this human protein may alter the pathobiology of malaria, hence the disease outcomes of the infection.

Source: Virulence

DOI: 10.1080/21505594.2026.2711530

Authors: Joo-Yie Chin, Laurent Rénia, Wenn-Chyau Lee

Institutions: University of Malaya, Agency for Science, Technology and Research, Nanyang Technological University

Language: English

Topic: Malaria Research and Control

Subfield: Public Health, Environmental and Occupational Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,557