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

Area of Science:

• * Malaria parasite biology
• * Host-pathogen interactions
• * Immunology and host response

Background:

• * Malaria parasite maturation within red blood cells (RBCs) is influenced by host factors like nutrition and circadian rhythms.
• * The impact of host inflammatory responses on malaria parasite development remains incompletely understood.

Purpose of the Study:

• * To investigate whether systemic host inflammation affects malaria parasite maturation rates.
• * To identify mechanisms by which inflammation might inhibit parasite development.

Main Methods:

• * Induction of systemic inflammation in mice using lipopolysaccharide (LPS) or acute Plasmodium infection.
• * In vitro culture of parasites with plasma from conditioned or infected mice.
• * Metabolomic analysis of host plasma.
• * Single-cell RNA sequencing (scRNA-seq) of Plasmodium parasites in vivo.

Main Results:

• * Systemic inflammation significantly slowed parasite maturation from one RBC generation to the next.
• * Plasma from inflamed hosts directly inhibited parasite maturation in vitro, indicating the presence of inhibitory factors.
• * Metabolomic profiling revealed significant plasma alterations and identified candidate inhibitory metabolites.
• * scRNA-seq showed rapid, broad impairment of transcriptional and translational activity in circulating Plasmodium trophozoites.

Conclusions:

• * Systemic host inflammation rapidly impacts malaria parasite maturation by altering plasma composition and directly affecting parasite gene expression.
• * Candidate inhibitory metabolites in plasma may contribute to the observed maturation delay.
• * This study reveals a novel mechanism where host inflammation limits malaria parasite growth in the bloodstream.