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Related Concept Videos

Malaria01:29

Malaria

Malaria pathogenesis in humans reflects a delicate interplay between parasite biology and host response. Clinical illness reflects a host’s immune response to the parasite’s asexual replication cycle, which is often asymptomatic in individuals with partial immunity. From the parasite's perspective, transmission between mosquito and human with minimal host pathology is evolutionarily advantageous. Among the six Plasmodium species infecting humans, P. falciparum and P. vivax dominate in global...
Anthelminthic Agents01:15

Anthelminthic Agents

Anthelmintic drugs differ significantly from antiparasitic therapies targeting protozoa, primarily due to differences in parasite biology. Whereas most protozoal treatments act on proliferating cells, anthelmintics are typically directed against mature, nonproliferative helminths. The therapeutic approach considers the helminth's reliance on neuromuscular coordination, glucose metabolism, and microtubular integrity for survival, reproduction, and localization within the host. Most anthelmintics...
Antiprotozoal Agents01:21

Antiprotozoal Agents

Leishmaniasis is a widespread parasitic disease caused by several Leishmania species. It affects millions of people each year and remains a major public health problem in endemic regions. First-line treatment relies on pentavalent antimonials, including meglumine antimoniate and sodium stibogluconate. Even so, how these drugs work has not been fully clear, especially their interaction with parasite-specific biochemical pathways. One key target is trypanothione reductase (TR), an enzyme that...

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An Experimental Model to Study Tuberculosis-Malaria Coinfection upon Natural Transmission of Mycobacterium tuberculosis and Plasmodium berghei
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Itaconate Has Limited Protective Effects in Experimental Malaria Models.

Fran Prenen1, Emilie Pollenus1, Hanne Meers1,2

  • 1Laboratory of Immunoparasitology, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.

European Journal of Immunology
|May 10, 2025
PubMed
Summary

Itaconate, a metabolite, does not worsen malaria. Studies show itaconate offers limited protection against malaria, contrary to recent findings, highlighting its therapeutic potential.

Keywords:
immunometabolisminflammationitaconatemalariamonocyte

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Area of Science:

  • Immunometabolism
  • Malaria Pathogenesis
  • Metabolite Therapeutics

Background:

  • Severe malaria involves metabolic dysregulation and inflammation, necessitating treatments targeting both.
  • Itaconate, produced by ACOD1, inhibits inflammation and glycolysis, showing promise in inflammatory diseases.
  • Elevated itaconate in malaria suggests a role, but its precise function remains unclear.

Purpose of the Study:

  • To investigate the role of itaconate in malaria pathogenesis.
  • To assess the therapeutic potential of itaconate in malaria.
  • To clarify the contribution of itaconate to malaria susceptibility or protection.

Main Methods:

  • Utilized Plasmodium berghei NK65 (severe) and Plasmodium chabaudi AS (mild) mouse models.
  • Employed 13C-tracer metabolomics to track itaconate production and distribution.
  • Analyzed ACOD1 knockout mice and 4-octyl itaconate treatment for disease impact.

Main Results:

  • Increased itaconate levels were detected in organs during infection, with inflammatory monocytes identified as producers.
  • ACOD1 knockout mice showed no significant changes in the severe malaria model (PbNK65).
  • ACOD1 deficiency exacerbated disease in the mild malaria model (PcAS), increasing weight loss, clinical scores, and parasitemia.

Conclusions:

  • Itaconate does not contribute to malaria susceptibility.
  • Itaconate provides a degree of protection in malaria, particularly in the PcAS model.
  • Findings challenge recent literature, suggesting itaconate's protective rather than detrimental role in malaria.