title: Spleen-Dependent Immune Protection Elicited by CpG Adjuvanted Reticulocyte-Derived Exosomes from Malaria Infection Is Associated with Changes in T cell Subsets' Distribution.
abstract: Reticulocyte-derived exosomes (rex) are 30-100 nm membrane vesicles of endocytic origin released during the maturation of reticulocytes to erythrocytes upon fusion of multivesicular bodies with the plasma membrane. Combination of CpG-ODN with rex obtained from BALB/c mice infected with the reticulocyte-prone non-lethalP. yoelii17X malaria strain (rexPy), had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected uponrexPy+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized withrexPy+CpG. Notably,rexPyimmunization of mice induced changes in PD1-memory T cells with effector phenotype. Proteomics analysis ofrexPyconfirmed their reticulocyte origin and demonstrated the presence of parasite antigens. Our studies thus prove, for what we believe is the first time, thatrexfrom reticulocyte-prone malarial infections are associated with splenic long-lasting memory responses. To try extrapolating these data to human infections,in vitroexperiments with spleen cells of human transplantation donors were performed. Plasma-derived exosomes from vivax malaria patients (exPv) were actively uptaken by human splenocytes and stimulated spleen cells leading to changes in T cell subsets.
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic - Universitat de Barcelona Barcelona, Spain.
authors.forename: Lorena
authors.initials: L
authors.lastname: Martín-Jaular
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic - Universitat de Barcelona Barcelona, Spain.
authors.forename: Armando
authors.initials: A
authors.lastname: de Menezes-Neto
authors.affiliation: REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research Institute Badalona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Monguió-Tortajada
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic - Universitat de Barcelona Barcelona, Spain.
authors.forename: Aleix
authors.initials: A
authors.lastname: Elizalde-Torrent
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic - Universitat de Barcelona Barcelona, Spain.
authors.forename: Míriam
authors.initials: M
authors.lastname: Díaz-Varela
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic - Universitat de BarcelonaBarcelona, Spain; REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research InstituteBadalona, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Fernández-Becerra
authors.affiliation: REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research Institute Badalona, Spain.
authors.forename: Francesc E
authors.initials: FE
authors.lastname: Borras
authors.affiliation: Centre de Recerca en Sanitat Animal, Institut de Recerca i Tecnologia Agroalimentàries, Universitat de BarcelonaBarcelona, Spain; Virology, Pirbright InstitutePirbright, UK.
authors.forename: Maria
authors.initials: M
authors.lastname: Montoya
authors.affiliation: ISGlobal, Barcelona Centre for International Health Research, Hospital Clínic - Universitat de BarcelonaBarcelona, Spain; REMAR-IVECAT Group, Germans Trias i Pujol Health Science Research InstituteBadalona, Spain; Catalan Institution for Research and Advanced StudiesBarcelona, Spain.
authors.forename: Hernando A
authors.initials: HA
authors.lastname: Del Portillo
keywords: PD-1 cells; effector memory T-cells; malaria; pD1-cells; reticulocyte-derived exosomes; spleen; vaccine