TREM-1-Linked Inflammatory Cargo in SARS-CoV-2-Stimulated Macrophage Extracellular Vesicles Drives Cellular Senescence and Impairs Antibacterial Defense

The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SAR...

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Main Authors: Pedro V. da Silva-Neto, Jonatan C. S. de Carvalho, Diana M. Toro, Bianca T. M. Oliveira, Juçara G. Cominal, Ricardo C. Castro, Maria A. Almeida, Cibele M. Prado, Eurico Arruda, Fabiani G. Frantz, Ana P. Ramos, Pietro Ciancaglini, Ronaldo B. Martins, Juliano C. da Silveira, Fausto Almeida, Kelen C. R. Malmegrim, Carlos A. Sorgi
Format: Article
Language:English
Published: MDPI AG 2025-04-01
Series:Viruses
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Online Access:https://www.mdpi.com/1999-4915/17/5/610
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Summary:The COVID-19 pandemic, caused by SARS-CoV-2, has significantly affected global health, with severe inflammatory responses leading to tissue damage and persistent symptoms. Macrophage-derived extracellular vesicles (EVs) are involved in the modulation of immune responses, but their involvement in SARS-CoV-2-induced inflammation and senescence remains unclear. Triggering receptors expressed on myeloid cell-1 (TREM-1) are myeloid cell receptors that amplify inflammation, described as a biomarker of the severity and mortality of COVID-19. This study investigated the composition and effects of macrophage-derived EVs stimulated by SARS-CoV-2 (MφV-EVs) on the recipient cell response. Our results, for the first time, show that SARS-CoV-2 stimulation modifies the cargo profile of MφV-EVs, enriching them with TREM-1 and miRNA-155 association, along with MMP-9 and IL-8/CXCL8. These EVs carry senescence-associated secretory phenotype (SASP) components, promote cellular senescence, and compromise antibacterial defenses upon internalization. Our findings provide evidence that MφV-EVs are key drivers of inflammation and immune dysfunction, underscoring their potential as therapeutic targets in COVID-19.
ISSN:1999-4915