Infected erythrocytes and plasma proteomics reveal a specific protein signature of severe malaria

ABSTRACT: Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), claims the life of 15 to 25% of admitted children despite treatment. P. falciparum infects and multiplies in human erythrocytes, contributing to anemia, parasite sequestration, and inflammation in the host. In this study, an unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to decipher the complex mechanisms underlying the pathophysiology of CM and the corresponding host-parasite interactions. A significant down-regulation of proteins from the ubiquitin-proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) was associated with infected erythrocytes from CM patients. Further functional analysis showed dysregulated iron metabolism and ferroptosis pathways associated with CM. At the plasma level, the samples clustered according to clinical presentation. Importantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger confirmation cohort (n=274). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroid precursors and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers.

INSTRUMENT(S): timsTOF Pro

ORGANISM(S): Plasmodium Falciparum Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Plasmodium Falciparum Malaria

SUBMITTER: Virginie Salnot  

LAB HEAD: Gwladys I.

PROVIDER: PXD043033 | Pride | 2024-02-01

REPOSITORIES: Pride