Frontiers in Immunology (Jan 2022)
Exosomes Recovered From the Plasma of COVID-19 Patients Expose SARS-CoV-2 Spike-Derived Fragments and Contribute to the Adaptive Immune Response
- Elisa Pesce,
- Nicola Manfrini,
- Nicola Manfrini,
- Chiara Cordiglieri,
- Spartaco Santi,
- Spartaco Santi,
- Alessandra Bandera,
- Alessandra Bandera,
- Alessandra Bandera,
- Andrea Gobbini,
- Paola Gruarin,
- Andrea Favalli,
- Mauro Bombaci,
- Alessandro Cuomo,
- Federica Collino,
- Federica Collino,
- Giulia Cricrì,
- Giulia Cricrì,
- Riccardo Ungaro,
- Andrea Lombardi,
- Andrea Lombardi,
- Davide Mangioni,
- Antonio Muscatello,
- Stefano Aliberti,
- Stefano Aliberti,
- Francesco Blasi,
- Francesco Blasi,
- Andrea Gori,
- Andrea Gori,
- Andrea Gori,
- Sergio Abrignani,
- Sergio Abrignani,
- Raffaele De Francesco,
- Raffaele De Francesco,
- Stefano Biffo,
- Stefano Biffo,
- Renata Grifantini
Affiliations
- Elisa Pesce
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Nicola Manfrini
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Nicola Manfrini
- Department of Biosciences, Università degli Studi di Milano, Milan, Italy
- Chiara Cordiglieri
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Spartaco Santi
- Unit of Bologna, Consiglio Nazionale delle Ricerche (CNR) Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”, Bologna, Italy
- Spartaco Santi
- Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Istituto Ortopedico Rizzoli, Bologna, Italy
- Alessandra Bandera
- Infectious Diseases Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Alessandra Bandera
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Alessandra Bandera
- Centre for Multidisciplinary Research in Health Science (MACH), Università degli Studi di Milano, Milan, Italy
- Andrea Gobbini
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Paola Gruarin
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Andrea Favalli
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Mauro Bombaci
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Alessandro Cuomo
- Department of Experimental Oncology, Istituto Europeo di Oncologia (IEO), European Institute of Oncology Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Milan, Italy
- Federica Collino
- Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Federica Collino
- 0Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy
- Giulia Cricrì
- Laboratory of Translational Research in Paediatric Nephro-Urology, Fondazione Ca’ Granda IRCCS Ospedale Maggiore Policlinico, Milan, Italy
- Giulia Cricrì
- 0Department of Clinical Sciences and Community Health, University of Milano, Milan, Italy
- Riccardo Ungaro
- Infectious Diseases Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Andrea Lombardi
- Infectious Diseases Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Andrea Lombardi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Davide Mangioni
- Infectious Diseases Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Antonio Muscatello
- Infectious Diseases Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Stefano Aliberti
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Stefano Aliberti
- 1Respiratory Unit and Cystic Fibrosis Adult Center, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
- Francesco Blasi
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Francesco Blasi
- 1Respiratory Unit and Cystic Fibrosis Adult Center, Respiratory Unit and Cystic Fibrosis Adult Center, Milan, Italy
- Andrea Gori
- Infectious Diseases Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
- Andrea Gori
- Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
- Andrea Gori
- Centre for Multidisciplinary Research in Health Science (MACH), Università degli Studi di Milano, Milan, Italy
- Sergio Abrignani
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Sergio Abrignani
- 2Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy
- Raffaele De Francesco
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Raffaele De Francesco
- 3Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
- Stefano Biffo
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- Stefano Biffo
- Department of Biosciences, Università degli Studi di Milano, Milan, Italy
- Renata Grifantini
- Istituto Nazionale Genetica Molecolare (INGM), Istituto Nazionale Genetica Molecolare “Romeo ed Enrica Invernizzi”, Milan, Italy
- DOI
- https://doi.org/10.3389/fimmu.2021.785941
- Journal volume & issue
-
Vol. 12
Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by beta-coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has rapidly spread across the globe starting from February 2020. It is well established that during viral infection, extracellular vesicles become delivery/presenting vectors of viral material. However, studies regarding extracellular vesicle function in COVID-19 pathology are still scanty. Here, we performed a comparative study on exosomes recovered from the plasma of either MILD or SEVERE COVID-19 patients. We show that although both types of vesicles efficiently display SARS-CoV-2 spike-derived peptides and carry immunomodulatory molecules, only those of MILD patients are capable of efficiently regulating antigen-specific CD4+ T-cell responses. Accordingly, by mass spectrometry, we show that the proteome of exosomes of MILD patients correlates with a proper functioning of the immune system, while that of SEVERE patients is associated with increased and chronic inflammation. Overall, we show that exosomes recovered from the plasma of COVID-19 patients possess SARS-CoV-2-derived protein material, have an active role in enhancing the immune response, and possess a cargo that reflects the pathological state of patients in the acute phase of the disease.
Keywords
- COVID-19
- SARS-CoV-2
- exosomes
- immune activation
- antigen-presenting cells (APCs)
- soluble mediators in immunity