Henderson Alexander G, Davis Joy M, Keith Johnathan D, Green Morgan E, Oden Ashley M, Rowe Steven M, Birket Susan E
Dept of Medicine and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA.
Dept of Medicine and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
Eur Respir J. 2022 Sep 7;60(3). doi: 10.1183/13993003.01032-2021. Print 2022 Sep.
Cystic fibrosis airway disease is characterised by chronic infection. Successful eradication strategies have been hampered by a poor understanding of the mechanisms underlying conversion to chronicity. The cystic fibrosis transmembrane conductance receptor (CFTR)-knockout (KO) rat harbours a progressive defect in mucociliary transport and viscosity. KO rats were infected before and after the appearance of the mucus defect, using a clinical mucoid-isolate of embedded in agarose beads. Young KO rats that were exposed to bacteria before the development of mucociliary transport defects resolved the infection and subsequent tissue damage. However, older KO rats that were infected in the presence of hyperviscous and static mucus were unable to eradicate bacteria, but instead had bacterial persistence through 28 days post-infection that was accompanied by airway mucus occlusion and lingering inflammation. Normal rats responded to infection with increased mucociliary transport to supernormal rates, which reduced the severity of a second bacterial exposure. We conclude that the aberrant mucus present in the CF airway permits persistence of in the lung.
囊性纤维化气道疾病的特征是慢性感染。由于对向慢性转变的潜在机制了解不足，成功的根除策略受到了阻碍。囊性纤维化跨膜传导受体（CFTR）基因敲除（KO）大鼠在黏液纤毛运输和黏度方面存在渐进性缺陷。在黏液缺陷出现之前和之后，使用嵌入琼脂糖珠的临床黏液样分离株对KO大鼠进行感染。在黏液纤毛运输缺陷出现之前接触细菌的年轻KO大鼠解决了感染及随后的组织损伤。然而，在存在高黏性和静止黏液的情况下被感染的老年KO大鼠无法根除细菌，而是在感染后28天内细菌持续存在，同时伴有气道黏液阻塞和持续炎症。正常大鼠对感染的反应是黏液纤毛运输增加至超常速率，这降低了第二次细菌暴露的严重程度。我们得出结论，CF气道中存在的异常黏液使细菌能够在肺部持续存在。
