Blood-derived exosomes released after the oral administration of heat-killed Enterococcus faecalis activate immunity

We aimed to examine the mechanism of heat-killed Enterococcus faecalis (HkEf) immunostimulatory effect when orally administered. Immunocompetent splenocytes from mice orally administered HkEf were assessed using flow cytometry. Immunocompetent cells were determined by culturing splenocytes with serum or blood derived-exosomes. In vitro studies evaluated the reaction between mouse splenocytes and exosomes purified and isolated from mice bone marrow-derived macrophages (BMDMs) treated with HkEf. Levels of dendritic cells, red pulp macrophages, and inactive NK cells were significantly higher in the HkEf-treated group. Red pulp macrophages and inactive NK cells were increased in splenocytes cultured with blood-derived exosomes from mice administered HkEf. Further, mouse splenocytes cultured with the HkEf-stimulated BMDMs-derived exosomes group had significantly higher levels of red pulp macrophages. Thus, HkEf was involved in host immunostimulation and exosomes were identified as mediators in immune response signaling. Further verification of the mechanism would be needed to fill in the gap between the present results and conclusions.