Host Reticulocyte Redox Attenuation Creates a Protective Niche for Artemisinin Tolerance in Plasmodium falciparum - PubMed
3 hours ago
- #malaria
- #host-parasite interaction
- #artemisinin tolerance
- Artemisinin tolerance in Plasmodium falciparum is linked to host reticulocytes, which offer a protective niche.
- Reticulocytes are preferentially invaded by P. falciparum, leading to faster asexual development compared to mature erythrocytes.
- Multi-omics analyses show reticulocytes provide a metabolically rich environment with enhanced antioxidant defenses and glutathione metabolism.
- Parasites in reticulocytes have reduced susceptibility to artemisinin and other redox-active antimalarials but not to drugs with non-oxidative mechanisms.
- Reticulocyte-resident parasites exhibit better survival and recrudescence after artemisinin exposure, indicating host-mediated drug tolerance.
- Host erythroid maturation state is a key determinant of antimalarial efficacy, with reticulocytes attenuating oxidative stress to promote parasite persistence.