Plasmodium vivax spleen-dependent protein 1 and its role in extracellular vesicles-mediated intrasplenic infections
Ayllon-Hermida, Alberto (Institut Germans Trias i Pujol)
Nicolau Fernández, Marc (Institut Germans Trias i Pujol)
Larrinaga, Ane M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Aparici-Herraiz, Iris (Institut Germans Trias i Pujol)
Tintó-Font, Elisabet (Barcelona Institute for Global Health (ISGlobal))
Llorà-Batlle, Oriol (Barcelona Institute for Global Health (ISGlobal))
Orban, Agnes (Malaria Research Unit. Institut Pasteur du Cambodge)
Yasnot, María Fernanda (Universidad de Córdoba)
Graupera, Mariona (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Esteller, M. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Popovici, Jean (Institut Pasteur (França))
Cortés, Alfred (Institució Catalana de Recerca i Estudis Avançats)
Del Portillo, Hernando A. (Institució Catalana de Recerca i Estudis Avançats)
Fernandez-Becerra, Carmen (Institut Germans Trias i Pujol)

Date:	2024
Abstract:	Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by Plasmodium vivax. Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the P. vivax spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into P. falciparum 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named P. vivax Spleen-Dependent Protein 1 (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from P. vivax-infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in P. vivax, a major challenge for malaria elimination.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2021/SGR-01554 Agencia Estatal de Investigación PID2019-111795RB-I00 Agencia Estatal de Investigación PID2022-142908OB-I00 "la Caixa" Foundation LCF/PR/HR21/52410021
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	Frontiers in cellular and infection microbiology, Vol. 14 (2024) , p. 1408451, ISSN 2235-2988

DOI: 10.3389/fcimb.2024.1408451
PMID: 38828264

14 p, 3.6 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
Articles > Research articles
Articles > Published articles