关键词: Pseudomonas aeruginosa airway epithelium cystic fibrosis human lung tissues intracellular infection

Mesh : Humans Cystic Fibrosis / microbiology complications Pseudomonas aeruginosa Female Male Adult Respiratory Mucosa / microbiology pathology Lung Transplantation Pseudomonas Infections / microbiology Lung / microbiology pathology Young Adult Epithelial Cells / microbiology

来  源:   DOI:10.1164/rccm.202308-1451OC

Abstract:
Rationale: Pseudomonas aeruginosa is the major bacterial pathogen colonizing the airways of adult patients with cystic fibrosis (CF) and causes chronic infections that persist despite antibiotic therapy. Intracellular bacteria may represent an unrecognized reservoir of bacteria that evade the immune system and antibiotic therapy. Although the ability of P. aeruginosa to invade and survive within epithelial cells has been described in vitro in different epithelial cell models, evidence of this intracellular lifestyle in human lung tissues is currently lacking. Objectives: To detect and characterize intracellular P. aeruginosa in CF airway epithelium from human lung explant tissues. Methods: We sampled lung explant tissues from patients with CF undergoing lung transplantation and non-CF lung donor control tissue. We analyzed lung tissue sections for the presence of intracellular P. aeruginosa using quantitative culture and microscopy, in parallel to histopathology and airway morphometry. Measurements and Main Results: P. aeruginosa was isolated from the lungs of seven patients with CF undergoing lung transplantation. Microscopic assessment revealed the presence of intracellular P. aeruginosa within airway epithelial cells in three of the seven patients analyzed at a varying but low frequency. We observed those events occurring in lung regions with high bacterial burden. Conclusions: This is the first study describing the presence of intracellular P. aeruginosa in CF lung tissues. Although intracellular P. aeruginosa in airway epithelial cells is likely relatively rare, our findings highlight the plausible occurrence of this intracellular bacterial reservoir in chronic CF infections.
摘要:
背景:铜绿假单胞菌(P.a.)是定植于成人囊性纤维化(CF)患者气道的主要细菌病原体,并导致尽管抗生素治疗仍持续的慢性感染。细胞内细菌可能代表逃避免疫系统和抗生素治疗的未识别的细菌库。虽然在不同的上皮细胞模型中已经描述了P.a.在上皮细胞内侵入和存活的能力,目前缺乏人类肺组织中这种细胞内生活方式的证据。
目的:检测和表征来自人肺外植体组织的CF气道上皮中的细胞内P.a.
方法:我们从接受肺移植的CF患者和非CF肺供体对照的肺外植体组织取样。我们分析了肺组织切片中细胞内P.A.的存在通过定量培养和显微镜,与组织病理学和气道形态学平行。
结果:P.a.从7例接受肺移植的CF患者的肺中分离。显微镜评估显示,7例患者中有3例存在气道上皮细胞内细胞内P.a.在一个变化但低的频率。我们观察到这些事件发生在具有高细菌负荷的肺区域。
结论:这是第一个描述CF肺组织中细胞内P.a.存在的研究。虽然气道上皮细胞中的细胞内P.a.可能是相对罕见的事件,我们的发现强调了这种细胞内细菌库在慢性CF感染中的合理发生。
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