脂多糖
肠沙门氏菌
化学
先天免疫系统
烟酰胺腺嘌呤二核苷酸磷酸
免疫系统
炎症
促炎细胞因子
一氧化氮
细胞因子
活性氧
微生物学
细胞生物学
生物
生物化学
免疫学
酶
大肠杆菌
有机化学
氧化酶试验
基因
受体
作者
Junyang Zhou,Jae-Jin Han,Yanxia Wei,Yugang Wang
标识
DOI:10.1096/fj.202400638r
摘要
Abstract Intestinal microbiota contributes to host defense against pathogens while avoiding the induction of inflammation in homeostatic conditions, but the mechanism is not fully understood. To investigate the potential role of the bacterial metabolite desaminotyrosine (DAT) in regulating host defense and inflammation, we pretreated mouse bone marrow‐derived macrophages (BMDMs) with DAT for 12 hours and then challenged with bacterial lipopolysaccharide (LPS). We found that DAT priming‐enhanced type I interferon response while selectively inhibiting proinflammatory interleukin (IL)‐6 production after exposure to LPS. This is related to the fact that DAT is a natural antioxidant determined by radical scavenging assay in a cell‐free system. DAT‐primed cells had increased levels of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) upon LPS stimulation. Countering the increased NADPH by supplementing extra oxidized NADP + to cells reversed DAT's effect on LPS‐induced Il‐6 and interferon‐stimulated gene expressions. DAT‐primed cells also were more resistant to oxidative stress‐induced generation of reactive oxygen species and cell death. DAT promoted the production of antimicrobial effector nitric oxide in a cellular redox‐dependent manner, leading to enhanced macrophage antimicrobial activity during Salmonella enterica infection. Our data suggest that DAT acts as a host‐microbiota crosstalk signal in shaping host immune defense and inflammatory response.
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