Autor: |
Emilio G. Vozza, Alanna M. Kelly, Clíodhna M. Daly, Sinead A. O’Rourke, Simon R. Carlile, Brenda Morris, Aisling Dunne, Rachel M. McLoughlin |
Jazyk: |
angličtina |
Rok vydání: |
2024 |
Předmět: |
|
Zdroj: |
Cell Death Discovery, Vol 10, Iss 1, Pp 1-11 (2024) |
Druh dokumentu: |
article |
ISSN: |
2058-7716 |
DOI: |
10.1038/s41420-024-02173-2 |
Popis: |
Abstract Staphylococcus aureus is an important human commensal which persistently colonizes up to 30% of the human population, predominantly within the nasal cavity. The commensal lifestyle of S. aureus is complex, and the mechanisms underpinning colonization are not fully understood. S. aureus can induce an immunosuppressive environment in the nasal tissue (NT) by driving IL-10 and IL-27 to facilitate nasal colonization, indicating that S. aureus has the capacity to modulate the local immune environment for its commensal habitation. Mounting evidence suggests commensal bacteria drive type 1 interferons (IFN-I) to establish an immunosuppressive environment and whilst S. aureus can induce IFN-I during infection, its role in colonization has not yet been examined. Here, we show that S. aureus preferentially induces IFN signaling in macrophages. This IFN-I in turn upregulates expression of proapoptotic genes within macrophages culminating in caspase-3 cleavage. Importantly, S. aureus was found to drive phagocytic cell apoptosis in the nasal tissue during nasal colonization in an IFN-I dependent manner with colonization significantly reduced under caspase-3 inhibition. Overall, loss of IFN-I signaling significantly diminished S. aureus nasal colonization implicating a pivotal role for IFN-I in controlling S. aureus persistence during colonization through its ability to induce phagocyte apoptosis. Together, this study reveals a novel strategy utilized by S. aureus to circumvent host immunity in the nasal mucosa to facilitate nasal colonization. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
|