# Heme oxygenase-1 and malaria pathogenesis

**Authors:** Theophilus Wakai, Shalom Chinedu, Israel Afolabi

PMC · DOI: 10.3389/fimmu.2026.1777520 · 2026-02-27

## TL;DR

This paper reviews how the enzyme HO-1 influences malaria severity, showing both protective and harmful effects, and explores its potential as a diagnostic and treatment target.

## Contribution

The paper highlights HO-1's dual role in malaria and its potential as a biomarker and therapeutic target.

## Key findings

- HO-1 protects against severe malaria by reducing inflammation and tissue damage in mice.
- Elevated HO-1 in human immune cells is linked to increased disease severity.
- HO-1 may serve as a biomarker and therapeutic target in malaria.

## 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 Plasmodium 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.

## Linked entities

- **Genes:** TED4 (Plant heme oxygenase (decyclizing) family protein) [NCBI Gene 817208], HMOX1 (heme oxygenase 1) [NCBI Gene 3162]
- **Diseases:** malaria (MONDO:0005136), cerebral malaria (MONDO:0005625)
- **Species:** Plasmodium (taxon 5820), Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** HMOX1 (heme oxygenase 1) [NCBI Gene 3162] {aka HMOX1D, HO-1, HSP32, bK286B10}
- **Diseases:** Malaria (MESH:D008288), cerebral malaria (MESH:D016779), infection (MESH:D007239), parasitic disease (MESH:D010272), tissue injury (MESH:D017695), organ dysfunction (MESH:D009102), hemolysis (MESH:D006461), inflammation (MESH:D007249)
- **Chemicals:** heme (MESH:D006418)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12982344/full.md

---
Source: https://tomesphere.com/paper/PMC12982344