@article{fdi:010088300,
  title = {{S}ystemic host inflammation induces stage-specific transcriptomic modification and slower maturation in malaria parasites},
  author = {{L}ansink, {L}. {I}. {M}. and {S}kinner, {O}. {P}. and {E}ngel, {J}. {A}. and {L}ee, {H}. {J}. and {S}oon, {M}. {S}. {F}. and {W}illiams, {C}. {G}. and {S}heela{N}air, {A}. and {P}ernold, {C}. {P}. {S}. and {L}aohamonthonkul, {P}. and {A}kter, {J}. and {S}toll, {T}. and {H}ill, {M}. {M}. and {T}alman, {A}rthur and {R}ussell, {A}. and {L}awniczak, {M}. and {J}ia, {X}. {X}. and {C}hua, {B}. and {A}nderson, {D}. and {C}reek, {D}. {J}. and {D}avenport, {M}. {P}. and {K}houry, {D}. {S}. and {H}aque, {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{M}aturation rates of malaria parasites within red blood cells ({RBC}s) can be influenced by host nutrient status and circadian rhythm; whether host inflammatory responses can also influence maturation remains less clear. {H}ere, we observed that systemic host inflammation induced in mice by an innate immune stimulus, lipopolysaccharide ({LPS}), or by ongoing acute {P}lasmodium infection, slowed the progression of a single cohort of parasites from one generation of {RBC} to the next. {I}mportantly, 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. {M}etabolomic assessments confirmed substantial alterations to the plasma of {LPS}-conditioned and acutely infected mice, and identified a small number of candidate inhibitory metabolites. {F}inally, we confirmed rapid parasite responses to systemic host inflammation in vivo using parasite sc{RNA}-seq, noting broad impairment in transcriptional activity and translational capacity specifically in trophozoites but not rings or schizonts. {T}hus, we provide evidence that systemic host inflammation rapidly triggered transcriptional alterations in circulating blood-stage {P}lasmodium trophozoites and predict candidate inhibitory metabolites in the plasma that may impair parasite maturation in vivo. {IMPORTANCEM}alaria parasites cyclically invade, multiply, and burst out of red blood cells. {W}e found that a strong inflammatory response can cause changes to the composition of host plasma, which directly slows down parasite maturation. {T}hus, our work highlights a new mechanism that limits malaria parasite growth in the bloodstream. {M}alaria parasites cyclically invade, multiply, and burst out of red blood cells. {W}e found that a strong inflammatory response can cause changes to the composition of host plasma, which directly slows down parasite maturation. {T}hus, our work highlights a new mechanism that limits malaria parasite growth in the bloodstream.},
  keywords = {malaria ; {P}lasmodium ; parasite maturation ; host inflammation ; single-cell ; transcriptomics ; metabolomics ; host-parasite interaction},
  booktitle = {},
  journal = {m{B}io},
  volume = {[{E}arly access]},
  numero = {},
  pages = {[21 p.]},
  ISSN = {2150-7511},
  year = {2023},
  DOI = {10.1128/mbio.01129-23},
  URL = {https://www.documentation.ird.fr/hor/fdi:010088300},
}