Exosomes released by Brucella‐infected macrophages inhibit the intracellular survival of Brucella by promoting the polarization of M1 macrophages

Abstract

Exosomes, membrane vesicles released extracellularly from cells, contain nucleic acids, proteins, lipids and other components, allowing the transfer of material information between cells. Recent studies reported the role of exosomes in pathogenic microbial infection and host immune mechanisms. Brucella‐invasive bodies can survive in host cells for a long time and cause chronic infection, which causes tissue damage. Whether exosomes are involved in host anti‐Brucella congenital immune responses has not been reported. Here, we extracted and identified exosomes secreted by Brucella melitensis M5 (Exo‐M5)‐infected macrophages, and performed in vivo and in vitro studies to examine the effects of exosomes carrying antigen on the polarization of macrophages and immune activation. Exo‐M5 promoted the polarization of M1 macrophages, which induced the significant secretion of M1 cytokines (tumour necrosis factor‐α and interferon‐γ) through NF‐κB signalling pathways and inhibited the secretion of M2 cytokines (IL‐10), thereby inhibiting the intracellular survival of Brucella. Exo‐M5 activated innate immunity and promoted the release of IgG2a antibodies that protected mice from Brucella infection and reduced the parasitaemia of Brucella in the spleen. Furthermore, Exo‐M5 contained Brucella antigen components, including Omp31 and OmpA. These results demonstrated that exosomes have an important role in immune responses against Brucella, which might help elucidate the mechanisms of host immunity against Brucella infection and aid the search for Brucella biomarkers and the development of new vaccine candidates.

Significance of extracellular vesicles in orchestration of immune responses in Mycobacterium tuberculosis infection

“…The exosomes secreted by Brucella melitensis -infected macrophages increased the polarization of macrophages towards M1 subtype. These exosomes contained Brucella antigen components and stimulated secretion of M1 cytokines (TNF and IFN-γ) through the NF-κB signaling pathway, inhibited the secretion of M2 cytokines (IL-10), and subsequently reduced the intracellular survival of Brucella ( Wang et al., 2023 ).…”