Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Pseudomonas Infection
Cystic Fibrosis Lung Transplant Recipients Have Suppressed Airway Interferon Responses during Pseudomonas Infection
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DOI：
10.1016/j.xcrm.2020.100055
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发表时间：
2020-07-21
影响因子：
14.3
通讯作者：
Greenland, John R.
中科院分区：
文献类型：
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作者：
Dugger, Daniel T.;Fung, Monica;Greenland, John R.
肺移植可以挽救终末期囊性纤维化（CF）的生命，但长期生存受到慢性肺移植功能障碍（CLAD）的限制。持续的上呼吸道铜绿假单胞菌（PsA）定植可以种植同种异体移植物。虽然新发PsA感染与非CF接受者的CLAD相关，但对于经历PsA再定植的CF接受者来说，这种关联不太清楚。在这里，我们评估主机和病原体的贡献，这种现象。在PsA感染的情况下，CF接受者的气道刷拭显示1型干扰素基因抑制。气道上皮细胞（AEC）培养物在不存在病原体或免疫细胞的情况下表现出类似的发现，与移植前CF AEC表型形成对比。1型干扰素启动子在CF AEC中相对高甲基化。该队列中的CF受试者具有更多的粘液PsA，而非CF PsA受试者具有降低的微生物组α多样性。移植前后的方案可能会受益于对这种宿主和微生物组平衡的考虑。
Lung transplantation can be lifesaving in end-stage cystic fibrosis (CF), but long-term survival is limited by chronic lung allograft dysfunction (CLAD). Persistent upper airway Pseudomonas aeruginosa (PsA) colonization can seed the allograft. While de novo PsA infection is associated with CLAD in non-CF recipients, this association is less clear for CF recipients experiencing PsA recolonization. Here, we evaluate host and pathogen contributions to this phenomenon. In the context of PsA infection, brushings from the airways of CF recipients demonstrate type 1 interferon gene suppression. Airway epithelial cell (AEC) cultures demonstrate similar findings in the absence of pathogens or immune cells, contrasting with the pre-transplant CF AEC phenotype. Type 1 interferon promoters are relatively hypermethylated in CF AECs. CF subjects in this cohort have more mucoid PsA, while non-CF PsA subjects have decreased microbiome alpha diversity. Peri-transplant protocols may benefit from consideration of this host and microbiome equilibrium.