Center for Experimental and Molecular Medicine (CEMM), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Amsterdam Infection and Immunity Institute (AI&II), Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Infect Immun. 2022 Jun 16;90(6):e0067421. doi: 10.1128/iai.00674-21. Epub 2022 May 19.
Peritonitis and abdominal sepsis remain major health problems and challenge for clinicians. Bruton's tyrosine kinase (Btk) is a versatile signaling protein involved in the regulation of B cell development and function, as well as innate host defense. In the current study, we aimed to explore the role of Btk in the host response during peritonitis and sepsis in mice induced by a gradually growing pathogenic strain of Escherichia coli bacteria. We found that Btk deficiency ameliorated antibacterial host defense during the late stage of E. coli-induced peritonitis. Btk was not required for cytokine and chemokine release in response to either E. coli or lipopolysaccharide and did not impact organ damage evoked by E. coli. Btk deficiency also did not alter neutrophil influx to the primary site of infection. However, the absence of Btk modestly enhanced phagocytosis of E. coli by neutrophils. These results indicate that Btk-mediated signaling is superfluous for inflammatory responses and remarkably detrimental for antibacterial defense during E. coli-induced peritonitis.
腹膜炎和腹腔感染仍是临床医生面临的重大健康问题和挑战。布鲁顿酪氨酸激酶(Btk)是一种多功能信号蛋白,参与 B 细胞发育和功能以及先天宿主防御的调节。在本研究中,我们旨在探讨 Btk 在逐渐生长的致病性大肠杆菌诱导的腹膜炎和脓毒症小鼠宿主反应中的作用。我们发现,Btk 缺乏可改善大肠杆菌诱导的腹膜炎后期的抗菌宿主防御。Btk 对于细胞因子和趋化因子的释放不是必需的,无论是对大肠杆菌还是脂多糖的反应,也不影响大肠杆菌引起的器官损伤。Btk 缺乏也不会改变中性粒细胞向感染的主要部位的流入。然而,Btk 的缺失适度增强了中性粒细胞对大肠杆菌的吞噬作用。这些结果表明,Btk 介导的信号传导对于大肠杆菌诱导的腹膜炎中的炎症反应是多余的,但对抗菌防御有显著的损害。