Subcutaneous injection of exosomes reduces symptom severity and mortality induced by Echinostoma caproni infection in BALB/c mice

Abstract

Recent studies have shown the importance of exosomes in the host-parasite relationship. These vesicles are an important part of the excretory/secretory pathway for proteins with the potential to alter immune responses. Therefore, in the present study, we examined the immunomodulatory role of exosomes in BALB/c mice using Echinostoma caproni as an experimental model of intestinal helminth infection. For this purpose, BALB/c mice were injected twice s.c. with purified exosomes of E. caproni, followed by experimental infection. We report a delay in the development of the parasite in mice immunised with exosomes, a concomitant reduced symptom severity and increased survival upon infection. Immunisations with exosomes evoked systemic antibody responses with high levels of IgM and IgG. IgG1, IgG2b and IgG3 are the subtypes responsible for the IgG increase. These antibodies showed specific recognition of exosomal proteins, indicating that these vesicles carry specific antigens that are involved in the humoral response. The administration of exosomes induced an increase of IFN-γ, IL-4 and TGF-β levels in the spleen of mice prior to infection. The subsequent infection with E. caproni resulted in a further increase of IL-4 and TGF-β, together with an abrupt overproduction of IL-10, suggesting the development of a Th2/Treg immune response. Our results show that the administration of exosomes primes the immune response in the host, which in turn can contribute to tolerance of the invader, reducing the severity of clinical signs in E. caproni infection.

Keywords: BALB/c mice; Echinostoma caproni; Exosome; Extracellular vesicles; Helminth; Immunomodulation.