School of Life Sciences, Ningxia University, Yinchuan, Ningxia 750021, China; Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
School of Life Sciences, Ningxia University, Yinchuan, Ningxia 750021, China; Key Lab of Ministry of Education for Protection and Utilization of Special Biological Resources in Western China, Ningxia University, Yinchuan, Ningxia 750021, China.
Int Immunopharmacol. 2024 Oct 25;140:112924. doi: 10.1016/j.intimp.2024.112924. Epub 2024 Aug 11.
Staphylococcus aureus (SA) is a common Gram-positive bacterium that activates inflammatory cells, expressing various cytokines and inducing an inflammatory response. Recent research revealed aconitate decarboxylase 1 (ACOD1) as a regulator of the immune response through various metabolic pathways, playing a dual role in the inflammatory response. However, the mechanism by which ACOD1 participates in the regulation of SA-induced inflammatory responses in macrophages remains unknown. Therefore, this study aims to investigate the function and underlying regulatory mechanisms of ACOD1 in SA-induced inflammatory response. This study reveals that SA induced a macrophage inflammatory response and upregulated ACOD1 expression. ACOD1 knockdown significantly inhibited SA-induced macrophage inflammatory response, attenuated SA-induced nuclear envelope wrinkling, and plasma membrane rupture, and suppressed the TLR4/NF-κB signaling pathway. Furthermore, ACOD1 knockdown reduced the inflammatory response and alleviated lung tissue injury and cellular damage, leading to decreased bacterial loads in the lungs of SA-infected mice. Collectively, these findings demonstrate that SA induces an inflammatory response in macrophages and increases ACOD1 expression. ACOD1 enhances SA-induced inflammatory responses via the TLR4/NF-κB signaling pathway. Our findings highlight the significant role of ACOD1 in mediating the inflammatory response in SA-infected macrophages and elucidate its molecular mechanism in regulating the SA-induced inflammatory response.
金黄色葡萄球菌（SA）是一种常见的革兰氏阳性菌，可激活炎症细胞，表达各种细胞因子并诱导炎症反应。最近的研究表明，顺乌头酸酶 1（ACOD1）通过多种代谢途径成为免疫反应的调节剂，在炎症反应中发挥双重作用。然而，ACOD1 参与调节巨噬细胞中 SA 诱导的炎症反应的机制尚不清楚。因此，本研究旨在探讨 ACOD1 在 SA 诱导的巨噬细胞炎症反应中的功能和潜在调节机制。本研究表明，SA 诱导巨噬细胞炎症反应并上调 ACOD1 的表达。ACOD1 敲低显著抑制 SA 诱导的巨噬细胞炎症反应，减弱 SA 诱导的核膜皱缩和质膜破裂，并抑制 TLR4/NF-κB 信号通路。此外，ACOD1 敲低减少了炎症反应，减轻了肺组织损伤和细胞损伤，导致 SA 感染小鼠肺部的细菌负荷降低。综上所述，这些发现表明 SA 诱导巨噬细胞炎症反应并增加 ACOD1 的表达。ACOD1 通过 TLR4/NF-κB 信号通路增强 SA 诱导的炎症反应。我们的研究结果强调了 ACOD1 在介导 SA 感染巨噬细胞中的炎症反应中的重要作用，并阐明了其在调节 SA 诱导的炎症反应中的分子机制。
