ACOD1 mediates Staphylococcus aureus-induced inflammatory response via the TLR4/NF-κB signaling pathway

• Published in: International immunopharmacology Vol. 140; p. 112924
• Main Authors: Dai, Fan, Zhang, Xuyang, Ma, Guilan, Li, Wu
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 25.10.2024
• Subjects: ACOD1; Animals; C57BL/6J mice; Carboxy-Lyases - genetics; Carboxy-Lyases - metabolism; Humans; Inflammation - immunology; Inflammation - metabolism; Inflammatory response; Lung - immunology; Lung - microbiology; Lung - pathology; Macrophage; Macrophages - immunology; Macrophages - metabolism; Mice; Mice, Inbred C57BL; NF-kappa B - metabolism; RAW 264.7 Cells; Signal Transduction - immunology; Staphylococcal Infections - immunology; Staphylococcus aureus; Staphylococcus aureus - immunology; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; ACOD1; Inflammatory response; C57BL/6J mice; Staphylococcus aureus; Macrophage
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112924

•Staphylococcus aureus induces inflammatory response and increases the expression of ACOD1 in macrophages.•ACOD1 knockdown reduces Staphylococcus aureus-induced inflammatory response, attenuates SA-induced nuclear envelope wrinkling, and plasma membrane rupture.•ACOD1 regulates Staphylococcus aureus-induced inflammatory response via the TLR4/NF-κB signaling pathway. 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.