Spleen-Dependent Immune Protection Elicited by CpG Adjuvanted Reticulocyte-Derived Exosomes from Malaria Infection Is Associated with Changes in T cell Subsets' Distribution

• Published in: Frontiers in cell and developmental biology Vol. 4; p. 131
• Main Authors: Martín-Jaular, Lorena, de Menezes-Neto, Armando, Monguió-Tortajada, Marta, Elizalde-Torrent, Aleix, Díaz-Varela, Míriam, Fernández-Becerra, Carmen, Borras, Francesc E, Montoya, Maria, Del Portillo, Hernando A
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media 16-11-2016; Frontiers Media S.A
• Subjects: Cell and Developmental Biology; Cèl·lules T; Malaria; Malària; T cells; effector memory T-cells; vaccine; spleen; reticulocyte-derived exosomes; malaria; PD-1 cells; pD1-cells
• ISSN: 2296-634X; 2296-634X
• DOI: 10.3389/fcell.2016.00131

Reticulocyte-derived exosomes (
) 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-lethal
17X malaria strain (
), had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected upon
+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized with
+CpG. Notably,
immunization of mice induced changes in PD1
memory T cells with effector phenotype. Proteomics analysis of
confirmed their reticulocyte origin and demonstrated the presence of parasite antigens. Our studies thus prove, for what we believe is the first time, that
from reticulocyte-prone malarial infections are associated with splenic long-lasting memory responses. To try extrapolating these data to human infections,
experiments with spleen cells of human transplantation donors were performed. Plasma-derived exosomes from vivax malaria patients (
) were actively uptaken by human splenocytes and stimulated spleen cells leading to changes in T cell subsets.