Extracellular vesicles from primary human macrophages stimulated with VIP or PACAP mediate anti-SARS-CoV-2 activities in monocytes through NF-κB signaling pathway.

Autor: Arteaga-Blanco LA; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Temerozo JR; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil; National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Tiné LPS; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Dantas-Pereira L; Laboratory of Cellular Biology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Sacramento CQ; Laboratory of Immunopharmacology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations, Center for Technological Development in Health, Fiocruz, Rio de Janeiro, 21040-360, Brazil., Fintelman-Rodrigues N; Laboratory of Immunopharmacology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations, Center for Technological Development in Health, Fiocruz, Rio de Janeiro, 21040-360, Brazil., Toja BM; Laboratory of Cellular and Molecular Cardiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, 21941-902, Brazil., Gomes Dias SS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., de Freitas CS; Laboratory of Immunopharmacology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Espírito-Santo CC; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Silva YP; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Frozza RL; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Bozza PT; Laboratory of Immunopharmacology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Menna-Barreto RFS; Laboratory of Cellular Biology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil., Souza TML; Laboratory of Immunopharmacology, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil; National Institute for Science and Technology on Innovation in Diseases of Neglected Populations, Center for Technological Development in Health, Fiocruz, Rio de Janeiro, 21040-360, Brazil., Bou-Habib DC; Laboratory on Thymus Research, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil; National Institute of Science and Technology on Neuroimmunomodulation, Oswaldo Cruz Institute/Fiocruz, Rio de Janeiro, 21040-360, Brazil. Electronic address: dumith.chequer@gmail.com.
Jazyk: angličtina
Zdroj: Microbes and infection [Microbes Infect] 2024 Nov-Dec; Vol. 26 (8), pp. 105400. Date of Electronic Publication: 2024 Jul 26.
DOI: 10.1016/j.micinf.2024.105400
Abstrakt: Infection by SARS-CoV-2 is associated with uncontrolled inflammatory response during COVID-19 severe disease, in which monocytes are one of the main sources of pro-inflammatory mediators leading to acute respiratory distress syndrome. Extracellular vesicles (EVs) from different cells play important roles during SARS-CoV-2 infection, but investigations describing the involvement of EVs from primary human monocyte-derived macrophages (MDM) on the regulation of this infection are not available. Here, we describe the effects of EVs released by MDM stimulated with the neuropeptides VIP and PACAP on SARS-CoV-2-infected monocytes. MDM-derived EVs were isolated by differential centrifugation of medium collected from cells cultured for 24 h in serum-reduced conditions. Based on morphological properties, we distinguished two subpopulations of MDM-EVs, namely large (LEV) and small EVs (SEV). We found that MDM-derived EVs stimulated with the neuropeptides inhibited SARS-CoV-2 RNA synthesis/replication in monocytes, protected these cells from virus-induced cytopathic effects and reduced the production of pro-inflammatory mediators. In addition, EVs derived from VIP- and PACAP-treated MDM prevented the SARS-CoV-2-induced NF-κB activation. Overall, our findings suggest that MDM-EVs are endowed with immunoregulatory properties that might contribute to the antiviral and anti-inflammatory responses in SARS-CoV-2-infected monocytes and expand our knowledge of EV effects during COVID-19 pathogenesis.
Competing Interests: Declaration of competing interest The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2024 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)
Databáze: MEDLINE