Host-Derived Linoleic Acid Promotes Malaria Pathogenesis by Enhancing Plasmodium Falciparum Proliferation

Abstract

Unveiling the mechanisms of host–parasite interactions in vivo in malaria can significantly advance the development of antimalarial strategies tailored to clinically and physiologically relevant contexts. By analyzing 396 paired global serum lipidomes from pediatric malaria patients sampled both before and during blood-stage infection, we discovered consistent alterations in the host lipidome across three ethnic groups, Gouin Mossi and Fulani, in Burkina Faso, West Africa. We identified infection-induced depletion of 47 host-derived lipids correlated with parasitemia and demonstrate that the parasite selectively scavenges linoleic acid-containing phospholipids to boost its proliferation. This finding was experimentally validated using parasite culture assays. Our integrative multi-omics approach, combining lipidomic and host-parasite transcriptomic data, further uncovered a Plasmodium falciparum transcriptional signature associated with lipid turnover in vivo. These results provide a high-resolution profile of lipidomic perturbations in malarial children and illustrate how paired clinical phenotyping, cross-ethnic population sampling, and multi-omics can illuminate key host-parasite interactions and uncover clinically relevant molecular nuances within the human host.

Keywords: Malaria, Host-parasite interactions, Lipidomics, Linoleic acid, Ethnicity