Proteomic characterization of exosomes derived from malaria-infected reticulocytes, in a murine malaria model

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. We previously found that immunization of mice with rex from BALB/c mice infected with the reticulocyte-prone non-lethal P. yoelii 17X malaria strain (rexPy) in combination with CpG-ODN promoted survival and long lasting protection of mice subsequently challenged with a lethal strain. Here, we show that rexPy-mediated protection is completely lost in splenectomized animals and such protection is achieved after passive transfer of splenocytes obtained from animals immunized with rexPy+CpG. Notably, rexPy immunization of mice induced non-exhausted memory T cell expansion 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 able to induce non-exhausted splenic long-lasting memory responses. In order to translate these results to humans, in vitro experiments with spleen cells of human transplantation donors were performed. Human splenocytes were able to actively capture plasma45 derived exosomes from patients infected with Plasmodium vivax (exPv) and stimulation of spleen cells with exPv for 72h lead to an increase in the number of T cells. All together, these data further support the value of reticulocyte-derived exosomes as a potential novel vaccine and platform against malaria.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Plasmodium Yoelii Mus Musculus (mouse)

TISSUE(S): Reticulocyte, Blood

DISEASE(S): Malaria

SUBMITTER: Armando Neto  

LAB HEAD: Hernando Antonio del Portillo

PROVIDER: PXD005048 | Pride | 2018-10-26

REPOSITORIES: Pride