Impact of dengue virus infection on the cytoadherence of Plasmodium vivax-infected erythrocytes

BACKGROUND Coinfections of Plasmodium parasites and the dengue virus have been linked to severe disease in some patients. The interactions between these two pathogens, particularly their effects on disease progression, highlight the clinical importance of understanding the mechanisms underlying the potential synergistic effects. OBJECTIVES The primary objective of this study was to investigate the adhesion dynamics of Plasmodium vivax-infected erythrocytes (Pv-iRBCs) in the presence of dengue virus (DENV) infection. By examining the interaction between these pathogens, the study aimed to provide insights into how coinfections might influence disease severity and progression. METHODS HepG2 cells were infected with DENV to observe changes in adhesion receptors and Pv-iRBCs adhesion capacity. Experiments using trypsin-treated Pv-iRBCs and UV-inactivated DENV dissected the adhesion process. Small molecule inhibitors were used to assess innate activation. ICAM-1 expression and its functional significance was quantified using a monoclonal anti-ICAM-1 antibody. FINDINGS We noted a significant increase in cytoadherence of Pv-iRBCs following DENV infection compared to mock conditions. Both trypsin treatment of Pv-iRBCs and UV inactivation of DENV led to a reduction in cytoadherence, underscoring their impact on the adhesion process. Notably, DENV infection induces an innate immune activation upregulating ICAM-1 on the cell surface and blocking with a monoclonal anti-ICAM-1 antibody significantly reduced the cytoadherence of Pv-iRBCs. MAIN CONCLUSIONS Elevated ICAM-1 levels on DENV-permissive cells may not only trap parasites within several niches but also contribute to endothelial and haematological disturbances in individuals with coinfections. Further research is required to fully elucidate the roles of cytoadherence and immune activation in the pathogenesis of dengue and malaria coinfections.