Li Cao, Wu Yuqing, Riehle Andrea, Ma Jie, Kamler Markus, Gulbins Erich, Grassmé Heike
Department of Molecular Biology, University of Duisburg-Essen, University Hospital, Essen, Germany.
Heartcenter, Essen-Huttrop GmbH, Essen, Germany.
Infect Immun. 2017 Apr 21;85(5). doi: 10.1128/IAI.00883-16. Print 2017 May.
plays an important role in sepsis, pneumonia, wound infections, and cystic fibrosis (CF), which is caused by mutations of the cystic fibrosis transmembrane conductance regulator (). Pulmonary infections in CF often occur very early and prior to colonization with other pathogens, in particular Here, we demonstrate that CF mice are highly susceptible to pulmonary infections with and fail to clear the pathogen during infection. is internalized by -deficient macrophages in the lung, but these macrophages are unable to kill intracellular bacteria. This failure might be caused by a defect in the fusion of phagosomes with lysosomes, while this process occurs rapidly in wild-type macrophages and serves to kill intracellular pathogens. Transplantation of infected -deficient alveolar macrophages into the lungs of noninfected CF mice is sufficient to induce pneumonia. This suggests that intracellular survival of in macrophages may allow the pathogen to chronically infect CF lungs.
在败血症、肺炎、伤口感染和囊性纤维化(CF)中起重要作用,囊性纤维化是由囊性纤维化跨膜传导调节因子()的突变引起的。CF患者的肺部感染通常很早就会发生,且在被其他病原体定植之前,尤其是在这里,我们证明CF小鼠对肺部感染高度敏感,并且在感染期间无法清除病原体。该病原体被肺部缺乏-的巨噬细胞内化,但这些巨噬细胞无法杀死细胞内的细菌。这种失败可能是由于吞噬体与溶酶体融合缺陷所致,而在野生型巨噬细胞中这个过程迅速发生并用于杀死细胞内病原体。将感染的缺乏-的肺泡巨噬细胞移植到未感染的CF小鼠肺部足以诱发肺炎。这表明病原体在巨噬细胞内的存活可能使其能够长期感染CF患者的肺部。