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Gut commensal metabolite rhamnose promotes macrophages phagocytosis by activating SLC12A4 and protects against sepsis in mice.
Li, Dongping; Wei, Rongjuan; Zhang, Xianglong; Gong, Shenhai; Wan, Meijuan; Wang, Fangzhao; Li, Jiaxin; Chen, Meiling; Liu, Ruofan; Wan, Yantong; Hong, Yinghao; Zeng, Zhenhua; Gu, Peng; Wang, Zhang; Selva Nandakumar, Kutty; Jiang, Yong; Zhou, Hongwei; Chen, Peng.
Afiliação
  • Li D; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Wei R; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Zhang X; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Gong S; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Wan M; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Wang F; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Li J; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Chen M; Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China.
  • Liu R; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Wan Y; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Hong Y; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Zeng Z; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Gu P; Department of Critical Care Medicine, Nanfang Hospital, Southern Medical University, Guangzhou 510000, China.
  • Wang Z; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • Selva Nandakumar K; Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen 518000, China.
  • Jiang Y; Institute of Ecological Sciences, School of Life Sciences, South China Normal University, Guangzhou 510000, China.
  • Zhou H; Department of Environmental and Biosciences, School of Business, Innovation and Sustainability, Kristian IV's väg 3, Halmstad University, Halmstad 30004, Sweden.
  • Chen P; Department of Pathophysiology, Guangdong Provincial Key Laboratory of Proteomics, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510000, China.
Acta Pharm Sin B ; 14(7): 3068-3085, 2024 Jul.
Article em En | MEDLINE | ID: mdl-39027244
ABSTRACT
Sepsis progression is significantly associated with the disruption of gut eubiosis. However, the modulatory mechanisms of gut microbiota operating during sepsis are still unclear. Herein, we investigated how gut commensals impact sepsis development in a pre-clinical model. Cecal ligation and puncture (CLP) surgery was used to establish polymicrobial sepsis in mice. Mice depleted of gut microbiota by an antibiotic cocktail (ABX) exhibited a significantly higher level of mortality than controls. As determined by metabolomics analysis, ABX treatment has depleted many metabolites, and subsequent supplementation with l-rhamnose (rhamnose, Rha), a bacterial carbohydrate metabolite, exerted profound immunomodulatory properties with a significant enhancement in macrophage phagocytosis, which in turn improved organ damage and mortality. Mechanistically, rhamnose binds directly to and activates the solute carrier family 12 (potassium-chloride symporter), member 4 (SLC12A4) in macrophages and promotes phagocytosis by activating the small G-proteins, Ras-related C3 botulinum toxin substrate1 (Rac1) and cell division control protein 42 homolog (Cdc42). Interestingly, rhamnose has enhanced the phagocytosis capacity of macrophages from sepsis patients. In conclusion, by identifying SLC12A4 as the host interacting protein, we disclosed that the gut commensal metabolite rhamnose is a functional molecular that could promote the phagocytosis capacity of macrophages and protect the host against sepsis.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article