Heme oxygenase-1 and malaria pathogenesis

Abstract

Malaria is a life-threatening parasitic disease and remains a major cause of morbidity and mortality worldwide. The clinical course of malaria ranges from uncomplicated infection to severe disease, driven by extensive hemolysis, inflammation, and oxidative stress. Heme oxygenase-1 (HO-1), an inducible enzyme involved in heme degradation, has been demonstrated to play a crucial role in the host's response to <i>Plasmodium</i> infection. Experimental and clinical studies suggest that HO-1 is strongly induced during malaria and plays a crucial role in regulating inflammation, oxidative damage, and tissue injury. In murine models, HO-1 induction confers protection against severe malaria complications, including cerebral malaria and organ dysfunction, partly by modulating pro-inflammatory cytokines and vascular permeability. Conversely, elevated HO-1 expression in specific immune cell populations has been associated with heightened inflammatory responses and disease severity in humans, highlighting its context-dependent effects. Here, we review the key roles of HO-1 in malaria pathogenesis, emphasising its dual protective and pathological functions, and discuss its potential relevance as a diagnostic and prognostic biomarker and as a therapeutic target.