Regnase-1 Deficiency Restrains Klebsiella pneumoniae Infection by Regulation of a Type I Interferon Response.
Regnase-1 Deficiency Restrains Klebsiella pneumoniae Infection by Regulation of a Type I Interferon Response.
复制标题
DOI：
10.1128/mbio.03792-21
复制
发表时间：
2021-02-22
期刊：
影响因子：
6.4
通讯作者：
Gaffen SL
中科院分区：
文献类型：
--
作者：
Trevejo-Nuñez G;Lin B;Fan L;Aggor FEY;Biswas PS;Chen K;Gaffen SL
过度炎症可引起组织损伤和自身免疫，有时伴有严重的发病率或死亡率。存在许多负反馈机制来防止不受控制的炎症，但这种抑制可能以次优的感染控制为代价。Regnase-1（MCPIP 1）是IL-17和LPS信号传导的反馈调节剂，结合并降解靶mRNA。因此，Reg 1缺陷在多种模型中加剧了自身免疫。然而，Reg 1在细菌免疫中的作用仍然不清楚。在这里，我们发现Reg 1缺陷的小鼠对肺炎克雷伯氏菌（KP）具有耐药性。Reg 1缺陷并不加速细菌根除。相反，Reg 1缺陷的肺泡巨噬细胞有升高的Ifnb 1和富集的I型IFN基因。KP感染期间IFNR的阻断逆转了疾病的改善。Reg 1不直接影响Ifnb 1的稳定性，但影响Irf 7的表达。因此，Reg 1抑制I型IFN信号传导，限制对KP的抗性，表明Reg 1可能是严重细菌感染的靶标。
Excessive inflammation can cause tissue damage and autoimmunity, sometimes accompanied by severe morbidity or mortality. Numerous negative feedback mechanisms exist to prevent unchecked inflammation, but this restraint may come at the cost of suboptimal infection control. Regnase-1 (MCPIP1), a feedback regulator of IL-17 and LPS signaling, binds and degrades target mRNAs. Consequently, Reg1 deficiency exacerbates autoimmunity in multiple models. However, the role of Reg1 in bacterial immunity remains poorly defined. Here, we show that mice deficient in Reg1 are resistant to Klebsiella pneumoniae (KP). Reg1 deficiency did not accelerate bacterial eradication. Rather, Reg1-deficient alveolar macrophages had elevated Ifnb1 and enrichment of type I IFN genes. Blockade of IFNR during KP infection reversed disease improvement. Reg1 did not impact Ifnb1 stability directly, but Irf7 expression was affected. Thus, Reg1 suppresses type I IFN signaling restricting resistance to KP, suggesting that Reg1 could potentially be a target in severe bacterial infections.
登录
查看更多内容
影响因子：
6.7
作者：
Ivin M;Dumigan A;de Vasconcelos FN;Ebner F;Borroni M;Kavirayani A;Przybyszewska KN;Ingram RJ;Lienenklaus S;Kalinke U;Stoiber D;Bengoechea JA;Kovarik P
通讯作者：
Kovarik P
DOI：
10.1093/cid/cix270
发表时间：
2017-07-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
--
作者：
Gorrie CL;Mirceta M;Wick RR;Edwards DJ;Thomson NR;Strugnell RA;Pratt NF;Garlick JS;Watson KM;Pilcher DV;McGloughlin SA;Spelman DW;Jenney AWJ;Holt KE
通讯作者：
Holt KE
DOI：
10.1165/rcmb.2018-0021oc
发表时间：
2019-02-01
影响因子：
6.4
作者：
Ahn, Danielle;Wickersham, Matthew;Prince, Alice
通讯作者：
Prince, Alice
影响因子：
7.7
作者：
Akaki K;Ogata K;Yamauchi Y;Iwai N;Tse KM;Hia F;Mochizuki A;Ishihama Y;Mino T;Takeuchi O
通讯作者：
Takeuchi O
影响因子：
30.3
作者：
Boxx GM;Cheng G
通讯作者：
Cheng G