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-lethal P. yoelii 17X malaria strain (rexPy), had been shown to induce survival and long lasting protection. Here, we show that splenectomized mice are not protected upon rexPy+CpG inmunizations and that protection is restored upon passive transfer of splenocytes obtained from animals immunized with rexPy+CpG. Notably, rexPy immunization of mice induced changes in PD1− memory T cells with effector phenotype. Proteomics analysis of rexPy confirmed their reticulocyte origin and demonstrated the presence of parasite antigens. Our studies thus prove, for what we believe is the first time, that rex from reticulocyte-prone malarial infections are associated with splenic long-lasting memory responses. To try extrapolating these data to human infections, in vitro experiments 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.

Proteomic analysis of extracellular vesicles from a Plasmodium falciparum Kenyan clinical isolate defines a core parasite secretome

“…Pf EVs contain not only parasite proteins, but also TLR agonist such as parasite nucleic acids (Abdi et al unpublished data) that might potentiate immune response 79 . In this context, immunisation of mice with P. yoelii EVs elicited immune response that provided protection against lethal infection 26 , 80 Further study of Pf EVs could therefore be of interest for vaccine development.…”

Characterisation of infection associated microRNA and protein cargo in extracellular vesicles ofTheileria annulatainfected leukocytes

“…For example, EV from Trypanosomes have been implicated in the development of anaemia (Szempruch et al, 2016), while EV from Plasmodium-infected red blood cells are important in malaria pathogenesis (Mantel et al, 2016). Tumour-derived EV are most often associated with immune suppression, while EV from Plasmodium-infected reticulocytes induce protection via their interaction with CD4 and CD8 cells (Martin-Jaular et al, 2016). Tumour-derived EV are most often associated with immune suppression, while EV from Plasmodium-infected reticulocytes induce protection via their interaction with CD4 and CD8 cells (Martin-Jaular et al, 2016).…”

“…EV are also involved in the initiation and/or regulation of immune responses: They can mediate the transfer of antigenic peptides from infected cells to antigen-presenting cells and can deliver either stimulatory or suppressive signals to regulate the induction and differentiation of immune responses (reviewed in Robbins and Morelli, 2014). Tumour-derived EV are most often associated with immune suppression, while EV from Plasmodium-infected reticulocytes induce protection via their interaction with CD4 and CD8 cells (Martin-Jaular et al, 2016).…”

Characterization of Plasmodium vivax Proteins in Plasma-Derived Exosomes From Malaria-Infected Liver-Chimeric Humanized Mice

“…Our group and others have already identified Plasmodium spp proteins associated with microvesicles and exosomes by proteomic approaches (Mantel et al, 2013 ; Martín-Jaular et al, 2016 ). In both cases, EVs have been obtained from culture supernatant of infected P. falciparum and P. yoelii infected RBCs, respectively.…”