Macrophages treated with interferons induce different responses in lymphocytes via extracellular vesicles
Flavia Giannessi,
Zulema Percario,
Valentina Lombardi,
Andrea Sabatini,
Alessandra Sacchi,
Veronica Lisi,
Luca Battistini,
Giovanna Borsellino,
Elisabetta Affabris,
Daniela F. Angelini
Affiliations
Flavia Giannessi
Neuroimmunology Unit, IRCCS Santa Lucia Foundation, Via Ardeatina 306-354, 00179 Rome, Italy; Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Zulema Percario
Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Valentina Lombardi
Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Andrea Sabatini
Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Alessandra Sacchi
Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Veronica Lisi
Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Luca Battistini
Neuroimmunology Unit, IRCCS Santa Lucia Foundation, Via Ardeatina 306-354, 00179 Rome, Italy
Giovanna Borsellino
Neuroimmunology Unit, IRCCS Santa Lucia Foundation, Via Ardeatina 306-354, 00179 Rome, Italy
Elisabetta Affabris
Laboratory of Molecular Virology and Antimicrobial Immunity, Department of Science, Roma Tre University, 00146 Rome, Italy
Daniela F. Angelini
Neuroimmunology Unit, IRCCS Santa Lucia Foundation, Via Ardeatina 306-354, 00179 Rome, Italy; Corresponding author
Summary: Limited information exists regarding the impact of interferons (IFNs) on the information carried by extracellular vesicles (EVs). This study aimed at investigating whether IFN-α2b, IFN-β, IFN-γ, and IFN-λ1/2 modulate the content of EVs released by primary monocyte-derived macrophages (MDM). Small-EVs (sEVs) were purified by size exclusion chromatography from supernatants of MDM treated with IFNs. To characterize the concentration and dimensions of vesicles, nanoparticle tracking analysis was used. SEVs surface markers were examined by flow cytometry. IFN treatments induced a significant down-regulation of the exosomal markers CD9, CD63, and CD81 on sEVs, and a significant modulation of some adhesion molecules, major histocompatibility complexes and pro-coagulant proteins, suggesting IFNs influence biogenesis and shape the immunological asset of sEVs. SEVs released by IFN-stimulated MDM also impact lymphocyte function, showing significant modulation of lymphocyte activation and IL-17 release. Altogether, our results show that sEVs composition and activity are affected by IFN treatment of MDM.
