Systemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites

2023

Article référencé dans le Web of Science WOS:001028094900001

Lansink L. I. M., Skinner O. P., Engel J. A., Lee H. J., Soon M. S. F., Williams C. G., SheelaNair A., Pernold C. P. S., Laohamonthonkul P., Akter J., Stoll T., Hill M. M., Talman Arthur, Russell A., Lawniczak M., Jia X. X., Chua B., Anderson D., Creek D. J., Davenport M. P., Khoury D. S., Haque A.

mBio, 2023, [Early access], p. [21 p.] ISSN 2150-7511

Maturation rates of malaria parasites within red blood cells (RBCs) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. Here, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide (LPS), or by ongoing acute Plasmodium infection, slowed the progression of a single cohort of parasites from one generation of RBC to the next. Importantly, plasma from LPS-conditioned or acutely infected mice directly inhibited parasite maturation during in vitro culture, which was not rescued by supplementation, suggesting the emergence of inhibitory factors in plasma. Metabolomic assessments confirmed substantial alterations to the plasma of LPS-conditioned and acutely infected mice, and identified a small number of candidate inhibitory metabolites. Finally, we confirmed rapid parasite responses to systemic host inflammation in vivo using parasite scRNA-seq, noting broad impairment in transcriptional activity and translational capacity specifically in trophozoites but not rings or schizonts. Thus, we provide evidence that systemic host inflammation rapidly triggered transcriptional alterations in circulating blood-stage Plasmodium trophozoites and predict candidate inhibitory metabolites in the plasma that may impair parasite maturation in vivo. IMPORTANCEMalaria parasites cyclically invade, multiply, and burst out of red blood cells. We found that a strong inflammatory response can cause changes to the composition of host plasma, which directly slows down parasite maturation. Thus, our work highlights a new mechanism that limits malaria parasite growth in the bloodstream. Malaria parasites cyclically invade, multiply, and burst out of red blood cells. We found that a strong inflammatory response can cause changes to the composition of host plasma, which directly slows down parasite maturation. Thus, our work highlights a new mechanism that limits malaria parasite growth in the bloodstream.

Santé : généralités [050] ; Entomologie médicale / Parasitologie / Virologie [052]

Fonds IRD [F B010088300]

fdi:010088300