Wen Junjie, Chen Chuxi, Luo Meiqun, Liu Xiaocong, Guo Jiading, Wei Tingting, Gu Xinyi, Gu Sinan, Ning Yunshan, Li Yan
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, China.
The First Clinical Medical School, Southern Medical University, Guangzhou, China.
Front Microbiol. 2021 Jul 8;12:692832. doi: 10.3389/fmicb.2021.692832. eCollection 2021.
() is one of the gram-negative bacteria that mainly colonize the stomach mucosa and cause many gastrointestinal diseases, such as gastritis, peptic ulcer, and gastric cancer. Macrophages play a key role in eradicating . Recent data have shown that Notch signaling could modulate the activation and bactericidal activities of macrophages. However, the role of Notch signaling in macrophages against remains unclear. In the present study, in the co-culture model of macrophages with , the inhibition of Notch signaling using γ-secretase decreased the expression of inducible nitric oxide synthase (iNOS) and its product, nitric oxide (NO), and downregulated the secretion of pro-inflammatory cytokine and attenuated phagocytosis and bactericidal activities of macrophages to . Furthermore, we identified that Jagged1, one of Notch signaling ligands, was both upregulated in mRNA and protein level in activated macrophages induced by . Clinical specimens showed that the number of Jagged1 macrophages in the stomach mucosa from -infected patients was significantly higher than that in healthy control. The overexpression of Jagged1 promoted bactericidal activities of macrophages against and siRNA-Jagged1 presented the opposite effect. Besides, the addition of exogenous rJagged1 facilitated the pro-inflammatory mediators of macrophages against , but the treatment of anti-Jagged1 neutralizing antibody attenuated it. Taken together, these results suggest that Jagged1 is a promoting molecule for macrophages against , which will provide insight for exploring Jagged1 as a novel therapeutic target for the control of infection.
(某种细菌名称)是主要定植于胃黏膜并引发多种胃肠道疾病(如胃炎、消化性溃疡和胃癌)的革兰氏阴性菌之一。巨噬细胞在根除(该细菌名称)中起关键作用。近期数据表明,Notch信号可调节巨噬细胞的激活及杀菌活性。然而,Notch信号在巨噬细胞抵御(该细菌名称)方面的作用仍不清楚。在本研究中,在巨噬细胞与(该细菌名称)的共培养模型中,使用γ-分泌酶抑制Notch信号会降低诱导型一氧化氮合酶(iNOS)及其产物一氧化氮(NO)的表达,下调促炎细胞因子的分泌,并减弱巨噬细胞对(该细菌名称)的吞噬和杀菌活性。此外,我们发现Notch信号配体之一的Jagged1在由(该细菌名称)诱导激活的巨噬细胞中,mRNA和蛋白水平均上调。临床标本显示,感染(该细菌名称)患者胃黏膜中Jagged1阳性巨噬细胞的数量显著高于健康对照。Jagged1的过表达促进巨噬细胞对(该细菌名称)的杀菌活性,而siRNA-Jagged1则呈现相反作用。此外,添加外源性rJagged1可促进巨噬细胞针对(该细菌名称)的促炎介质产生,但抗Jagged1中和抗体处理则会减弱这种作用。综上所述,这些结果表明Jagged1是巨噬细胞抵御(该细菌名称)的促进分子,这将为探索Jagged1作为控制(该细菌名称)感染的新型治疗靶点提供思路。