Host Immune Modulation by Plasmodium-Derived Epigenetic Factors in Severe and Cerebral Malaria

Zakaria Ali

Department of Pharmacy Kampala International University Uganda

Email:ali.zakaria@studwc.kiu.ac.ug

ABSTRACT

Plasmodium falciparum infection triggered complex host immune responses that determined disease severity, with cerebral malaria representing the most lethal complication characterized by profound neuroinflammation, endothelial dysfunction, and blood-brain barrier disruption. Emerging evidence indicates that parasite-derived epigenetic factors, including histones, nucleosomes, extracellular vesicles, and microRNAs, actively modulate host immune signaling pathways and contribute to immunopathology. This review examined the mechanisms by which Plasmodium-derived epigenetic factors influenced host immune responses and evaluated their contribution to the pathogenesis of severe and cerebral malaria. A comprehensive analysis of recent literature focused on parasite epigenetic regulators, host immune modulation, inflammatory pathways, and cerebral malaria pathophysiology was conducted. Plasmodium releases histones, DNA complexes, and extracellular vesicles during schizont rupture that activate toll-like receptors, induce proinflammatory cytokine cascades, promote endothelial activation, and trigger neutrophil extracellular trap formation. Parasite-derived microRNAs transferred via extracellular vesicles reprogrammed host gene expression, suppressing antimalarial responses while enhancing inflammatory pathways. Epigenetic modifications in host immune cells, including altered histone acetylation and DNA methylation patterns, establish persistent immune dysfunction and contribute to cytokine storm generation. These mechanisms collectively drove severe malaria complications, including cerebral pathology, respiratory distress, and metabolic acidosis. Plasmodium-derived epigenetic factors represented critical mediators of immunopathology in severe malaria through multifaceted modulation of innate and adaptive immunity. Understanding these molecular interactions provided opportunities for developing host-directed therapies that mitigated excessive inflammation while preserving antimalarial immune responses and improving clinical outcomes in life-threatening malaria.

Keywords: Cerebral malaria, Plasmodium falciparum, Epigenetic regulation, Immune modulation, Extracellular vesicles.

CITE AS: Zakaria Ali (2026). Host Immune Modulation by Plasmodium-Derived Epigenetic Factors in Severe and Cerebral Malaria. RESEARCH INVENTION JOURNAL OF BIOLOGICAL AND APPLIED SCIENCES 6(1):87-93. https://doi.org/10.59298/RIJBAS/2026/618793