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 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.
Authors
- Ronaldo B. Martins (ORCID: https://orcid.org/0000-0002-8902-5962)
- Fabiani Gai Frantz (ORCID: https://orcid.org/0000-0001-6960-2438)
- Juliano Coelho da Silveira (ORCID: https://orcid.org/0000-0002-4796-6393)
- Ricardo Cardoso Castro (ORCID: https://orcid.org/0000-0002-3810-2534)
- Ana Paula Ramos (ORCID: https://orcid.org/0000-0001-6200-8989)
- Fausto Bruno dos Reis Almeida (ORCID: https://orcid.org/0000-0002-3782-3698)
- Diana Mota Toro (ORCID: https://orcid.org/0000-0002-1003-3848)
- Carlos A. Sorgi (ORCID: https://orcid.org/0000-0001-7528-9935)
- Kelen Cristina Ribeiro Malmegrim (ORCID: https://orcid.org/0000-0002-9303-0086)
- Pedro V. da Silva‐Neto (ORCID: https://orcid.org/0000-0003-1209-9346)
- Cibele M. Prado (ORCID: https://orcid.org/0000-0003-4321-0879)
- Pietro Ciancaglini (ORCID: https://orcid.org/0000-0002-2785-1345)
- Juçara Gastaldi Cominal (ORCID: https://orcid.org/0000-0002-8872-338X)
- Eurico Arruda (ORCID: https://orcid.org/0000-0002-0978-410X)
- Jonatan C. S. de Carvalho (ORCID: https://orcid.org/0000-0001-8776-5417)
- M. Almeida (ORCID: https://orcid.org/0009-0004-0529-4519)
- B. Oliveira (ORCID: https://orcid.org/0000-0002-6433-9551)
Institutions
- Universidade de Ribeirão Preto (BR)
- Universidade de São Paulo (BR)
- Universidade Federal do Amazonas (BR)
Publication Details
- Journal
- Viruses
- Published
- 2025-04-24
- DOI
- https://doi.org/10.3390/v17050610
- Citations
- 1
- Primary Topic
- Inflammation biomarkers and pathways
- Type
- article
- Field-Weighted Citation Impact
- 0.80
Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Faculdade de Zootecnia e Engenharia de Alimentos, Universidade de São Paulo