{"doi":"10.3390/microorganisms13081859","title":"Pharmacologic Inhibition of Erythrocyte Ferroportin Expression Exacerbates Plasmodium Infection","abstract":"Plasmodium parasites rely on host iron for survival and replication, making host iron availability a critical determinant of malaria pathogenesis. Central to iron homeostasis is the hepcidin–ferroportin regulatory axis, where hepcidin suppresses iron export by inducing ferroportin degradation, thus modulating systemic and cellular iron availability. In the Plasmodium infection model (P. yoelii), we observed a significant downregulation of hepatic hepcidin expression, accompanied by an increase in hepatic ferroportin expression. On the contrary, RBC-ferroportin protein level was notably suppressed upon P. yoelii infection. Given these findings, we aim to investigate the role of a ferroportin inhibitor in Plasmodium infection. In a P. yoelii mouse model, treatment with an oral ferroportin inhibitor, VIT-2763 (Vamifeport) increased parasitemia, accompanied by increased levels of pro-inflammatory cytokines, erythropoietin, and liver injury markers. In P. yoelii infected mice, VIT-2763 treatment suppressed hepcidin expression and increased ferroportin expression in hepatocytes, while reducing ferroportin protein levels in RBCs. VIT-2763 mediated exacerbation of P. yoelii infection reveals the tissue-specific regulation of ferroportin in hepatocytes and RBCs, underscoring the therapeutic potential of modulating the hepcidin–ferroportin axis as an intervention strategy in malaria.","journal":"Microorganisms","year":2025,"id":572245,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1478884,"name":"Benjamin Frederick Theis","orcid":null,"position":1,"is_corresponding":false},{"id":1478442,"name":"Jun Sung Park","orcid":"0000-0002-4028-8155","position":2,"is_corresponding":false},{"id":901773,"name":"Amira F. Gohara","orcid":"0000-0001-7068-2244","position":3,"is_corresponding":false},{"id":278273,"name":"Matam Vijay–Kumar","orcid":"0000-0002-8732-0167","position":4,"is_corresponding":false},{"id":278270,"name":"Beng San Yeoh","orcid":"0000-0002-7723-8733","position":5,"is_corresponding":false},{"id":278269,"name":"Piu Saha","orcid":"0000-0003-0626-398X","position":6,"is_corresponding":false},{"id":1478883,"name":"Sareh Zeydabadinejad","orcid":null,"position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-19T02:57:23.653298Z","pmid":"40871363","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}