Vozza Emilio G, Kelly Alanna M, Daly Clíodhna M, O'Rourke Sinead A, Carlile Simon R, Morris Brenda, Dunne Aisling, McLoughlin Rachel M
Host-Pathogen Interactions Group, School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
Molecular Immunology Group, School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.
Cell Death Discov. 2024 Sep 13;10(1):403. doi: 10.1038/s41420-024-02173-2.
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.
金黄色葡萄球菌是一种重要的人体共生菌，在高达30%的人群中持续定植，主要在鼻腔内。金黄色葡萄球菌的共生生活方式很复杂，其定植的潜在机制尚未完全了解。金黄色葡萄球菌可通过驱动白细胞介素-10和白细胞介素-27在鼻组织（NT）中诱导免疫抑制环境，以促进鼻腔定植，这表明金黄色葡萄球菌有能力调节局部免疫环境以实现其共生栖息。越来越多的证据表明，共生细菌驱动1型干扰素（IFN-I）建立免疫抑制环境，虽然金黄色葡萄球菌在感染期间可诱导IFN-I，但其在定植中的作用尚未得到研究。在此，我们表明金黄色葡萄球菌优先在巨噬细胞中诱导IFN信号传导。这种IFN-I反过来上调巨噬细胞内促凋亡基因的表达，最终导致半胱天冬酶-3裂解。重要的是，发现金黄色葡萄球菌在鼻腔定植期间以IFN-I依赖的方式驱动鼻组织中的吞噬细胞凋亡，在半胱天冬酶-3抑制下定植显著减少。总体而言，IFN-I信号传导缺失显著减少了金黄色葡萄球菌的鼻腔定植，这表明IFN-I通过其诱导吞噬细胞凋亡的能力在控制定植期间金黄色葡萄球菌的持续性方面起着关键作用。总之，这项研究揭示了金黄色葡萄球菌在鼻黏膜中规避宿主免疫以促进鼻腔定植所采用的一种新策略。
