Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils.
Transcriptional firing represses bactericidal activity in cystic fibrosis airway neutrophils.
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DOI：
10.1016/j.xcrm.2021.100239
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发表时间：
2021-04-20
期刊：
影响因子：
--
通讯作者：
Tirouvanziam R
中科院分区：
文献类型：
--
作者：
Margaroli C;Moncada-Giraldo D;Gulick DA;Dobosh B;Giacalone VD;Forrest OA;Sun F;Gu C;Gaggar A;Kissick H;Wu R;Gibson G;Tirouvanziam R
中性粒细胞通常被认为是终末分化和准备杀死细菌。在慢性疾病中，如囊性纤维化（CF），一个无法解释的悖论是大量中性粒细胞的存在与长期的细菌感染。在这里，我们发现在体内和体外转运模型中招募到CF气道的中性粒细胞显示出快速和广泛的转录激活，导致合成代谢基因上调和抗菌基因下调。新转录的rna被相应蛋白质的出现所反映，证实在这些细胞中有活性翻译。RNA聚合酶II和III抑制剂α-amanitin可恢复关键抗菌基因的表达，提高CF气道中性粒细胞体外和短期离体痰培养的杀菌能力。总的来说，我们的研究结果表明，中性粒细胞的可塑性在炎症部位通过RNA和蛋白质合成受到调节，从而导致影响其规范功能（即细菌清除）的适应性。嗜中性粒细胞对CF气道的适应导致其抗菌基因的下调转录阻断恢复CF气道中性粒细胞的杀菌能力嗜中性粒细胞通常被认为是终末分化的，并准备杀死细菌。在这里，Margaroli等人表明，人类中性粒细胞在迁移到囊性纤维化肺后具有转录和翻译可塑性，从而导致适应，甚至可以影响规范功能（即细菌清除）。
Neutrophils are often considered terminally differentiated and poised for bacterial killing. In chronic diseases such as cystic fibrosis (CF), an unexplained paradox pits massive neutrophil presence against prolonged bacterial infections. Here, we show that neutrophils recruited to CF airways in vivo and in an in vitro transmigration model display rapid and broad transcriptional firing, leading to an upregulation of anabolic genes and a downregulation of antimicrobial genes. Newly transcribed RNAs are mirrored by the appearance of corresponding proteins, confirming active translation in these cells. Treatment by the RNA polymerase II and III inhibitor α-amanitin restores the expression of key antimicrobial genes and increases the bactericidal capacity of CF airway neutrophils in vitro and in short-term sputum cultures ex vivo. Broadly, our findings show that neutrophil plasticity is regulated at the site of inflammation via RNA and protein synthesis, leading to adaptations that affect their canonical functions (i.e., bacterial clearance). Neutrophils recruited to cystic fibrosis airways undergo de novo RNA transcription Neutrophil adaptation to CF airways leads to downregulation of their antimicrobial genes Transcriptional blockade restores CF airway neutrophil bactericidal capacity Neutrophils are often considered terminally differentiated and poised for bacterial killing. Here, Margaroli et al. show that human neutrophils are transcriptionally and translationally plastic after migration into the cystic fibrosis lung, leading to adaptations that can affect even canonical functions (i.e., bacterial clearance).
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影响因子：
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影响因子：
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DOI：
10.4049/jimmunol.1500312
发表时间：
2015-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ingersoll SA;Laval J;Forrest OA;Preininger M;Brown MR;Arafat D;Gibson G;Tangpricha V;Tirouvanziam R
通讯作者：
Tirouvanziam R