Abstract
Exosomes are 30–100-nm membrane vesicles of endocytic origin that are released after the fusion of multivesicular bodies (MVBs) with the plasma membrane. While initial studies suggested that the role of exosomes was limited to the removal of proteins during the maturation of reticulocytes to erythrocytes, recent studies indicate that they are produced by different types of cells and are involved in promoting inter-cellular communication and antigen presentation. Here, we describe the isolation and characterization of exosomes from peripheral blood of BALB/c mice infected with the reticulocyte-prone non-lethal Plasmodium yoelii 17X strain. Importantly, proteomic analysis revealed the presence of parasite proteins in these vesicles. Moreover, immunization of mice with purified exosomes elicited IgG antibodies capable of recognizing P. yoelii-infected red blood cells. Furthermore, lethal challenge of immunized mice with the normocyte-prone lethal P. yoelii 17XL strain caused a significant attenuation in the course of parasitaemia, increased survival time, and altered the cell tropism to reticulocytes. These results were obtained also when the exosomes were isolated from a P. yoelii-infected reticulocyte culture indicating that reticulocyte-derived exosomes carry antigens and are involved in immune modulation. Moreover, inclusion of CpG ODN 1826 in exosome immunizations elicited IgG2a and IgG2b antibodies and promoted survival, clearance of parasites and subsequent sterile protection of 83% of the animals challenged with P. yoelli 17XL. To our knowledge, this is the first report of immune responses elicited by exosomes derived from reticulocytes opening new avenues for the modulation of anti-malaria responses.
Highlights
Exosomes are 30–100-nm membrane vesicles formed by endocytosis of segments of the plasma membrane
To determine whether exosomes derived from malaria-infected mice contain parasite proteins, we purified exosomes from peripheral blood of BALB/c mice infected with P. yoelii 17X at approximately two weeks post-infection (p.i.), when reticulocytosis reached 60–90%
CD107a (Lamp1) was found in vesicles isolated from blood of infected mice indicating that they were originated from an internal compartment and were not plasma membrane fragments
Summary
Exosomes are 30–100-nm membrane vesicles formed by endocytosis of segments of the plasma membrane. The internalized segment generates multivesicular bodies (MVBs) containing small vesicles that are released as exosomes following fusion of the MVBs with the plasma membrane [1]. Described as a reticulocyte cargo-disposal mechanism for maturation to erythrocytes [2], exosomes are known to be secreted by many different types of cells, including dendritic cells, macrophages, B cells, and tumor cells [1,3,4]. The role of exosomes in antigen presentation and immune modulation has been amply demonstrated in different infections including Salmonella, Mycobacterium, and Toxoplasma where exosomes released by infected cells contain microbial proteins [1,6]. The role of exosomes in antigen presentation in malaria, has not been described
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