Mammalian host microRNA response to plasmodial infection: role as therapeutic target and potential biomarker.

The appearance of increasing drug resistance in apicomplexan intracellular Plasmodium falciparum presents a significant challenge. P. falciparum infection results in cerebral malaria (CM), causing irreversible damage to the brain leading to high mortality cases. To enhance the clinical outcome of the disease, further research is required to identify new molecular targets involved in disease manifestations. Presently, the role of non-coding microRNAs (miRNAs) derived from different cells implicated in CM pathogenesis is still barely understood. Despite the absence of miRNA machinery in Plasmodium, host-parasite interactions can lead to disease severity or impart resistance to malaria. Cytoadherence and sequestration of parasitized RBCs dysregulate the miRNA profile of brain endothelial cells, leukocytes, monocytes, and platelets, disrupting blood-brain barrier integrity and activating inflammatory signaling pathways. The abundance of miRNA in blood plasma samples of CM patients directly correlates to cerebral symptoms compared to non-CM patients and healthy individuals. Moreover, the differential host-miRNA signatures distinguish P. falciparum from P. vivax infection. Here, we review the diverse functions of host-miRNA, either protective, pathogenic, or a combination of the two, which may act as prognostic markers and novel antimalarial drug targets.