Inflammasome-Derived Exosomes Activate NF-κB Signaling in Macrophages

Exosomes are secreted small vesicles
that mediate various biological
processes, such as tumorigenesis and immune response. However, whether
the inflammasome signaling leads to the change of constituent of exosomes
and its roles in immune response remains to be determined. We isolated
the exosomes from macrophages with treatment of mock, endotoxin, or
endotoxin/nigericin. A label-free quantification method by MS/MS was
used to identify the components of exosomes. In total, 2331 proteins
were identified and 513 proteins were exclusively detected in exosomes
with endotoxin and nigericin treatment. The differentially expressed
proteins were classified by Gene Ontology and KEGG pathways. The immune
response-related proteins and signaling pathways were specifically
enriched in inflammasome-derived exosomes. Moreover, we treated macrophages
with the exosomes from different stimulation. We found that inflammasome-derived
exosomes directly activate NF-κB signaling pathway, while the
control or endotoxin-derived exosomes have no effect. The inflammatory
signaling was amplified in neighbor cells in an exosome-dependent
way. The inflammasome-derived exosomes might be used to augment the
immune response in disease treatment, and preventing the transfer
of these exosomes might ameliorate autoimmune diseases.