ZKSCAN3 in severe bacterial lung infection and sepsis-induced immunosuppression.
ZKSCAN3 in severe bacterial lung infection and sepsis-induced immunosuppression.
复制标题
DOI：
10.1038/s41374-021-00660-z
复制
发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Ouyang X;Becker E Jr;Bone NB;Johnson MS;Craver J;Zong WX;Darley-Usmar VM;Zmijewski JW;Zhang J
败血症患者的死亡率在一定程度上与继发性肺部感染和呼吸衰竭的高风险有关。鉴于吞噬溶酶体在细胞内杀灭病原微生物中起重要作用，我们研究了脓毒症后免疫抑制相关的严重肺部感染如何影响吞噬溶酶体的生物发生。在铜绿假单胞菌诱导的肺炎小鼠中，我们发现吞噬体和溶酶体的消耗，微管相关蛋白轻链3-II （LC3-II）和溶酶体相关膜蛋白（LAMP1）的数量减少。我们还发现转录因子E3 （TFE3）和转录因子EB （TFEB）的缺失，它们是编码自噬和溶酶体蛋白的基因转录的重要激活因子。这些事件与ZKSCAN3的表达增加有关，ZKSCAN3是编码自噬和溶酶体蛋白的基因转录的抑制因子。与野生型小鼠相比，Zkscan3−/−小鼠的自噬-溶酶体途径相关基因的表达增加，肺部对铜绿假单胞菌的杀伤也增强。这些发现强调了ZKSCAN3参与严重肺部感染的应答，包括由于免疫抑制而对继发性细菌感染的易感性。
The mortality rates among patients who initially survive sepsis are, in part, associated with a high risk of secondary lung infections and respiratory failure. Given that phagolysosomes are important for intracellular killing of pathogenic microbes, we investigated how severe lung infections associated with post-sepsis immunosuppression affect phagolysosome biogenesis. In mice with P. aeruginosa-induced pneumonia, we found a depletion of both phagosomes and lysosomes, as evidenced by decreased amounts of microtubule associated protein light chain 3-II (LC3-II) and lysosomal-associated membrane protein (LAMP1). We also found a loss of transcription factor E3 (TFE3) and transcription factor EB (TFEB), which are important activators for transcription of genes encoding autophagy and lysosomal proteins. These events were associated with increased expression of ZKSCAN3, a repressor for transcription of genes encoding autophagy and lysosomal proteins. Zkscan3−/− mice had increased expression of genes involved in the autophagy-lysosomal pathway along with enhanced killing of P. aeruginosa in the lungs, as compared to wild-type mice. These findings highlight the involvement of ZKSCAN3 in response to severe lung infection, including susceptibility to secondary bacterial infections due to immunosuppression.
登录
查看更多内容
影响因子：
37.3
作者：
Bryant A;Palma CA;Jayaswal V;Yang YW;Lutherborrow M;Ma DD
通讯作者：
Ma DD
影响因子：
120.7
作者：
Boomer, Jonathan S.;To, Kathleen;Chang, Kathy C.;Takasu, Osamu;Osborne, Dale F.;Walton, Andrew H.;Bricker, Traci L.;Jarman, Stephen D., II;Kreisel, Daniel;Krupnick, Alexander S.;Srivastava, Anil;Swanson, Paul E.;Green, Jonathan M.;Hotchkiss, Richard S.
通讯作者：
Hotchkiss, Richard S.
DOI：
10.1038/nri3552
发表时间：
2013-12
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
2.4
作者：
Li, Ming-xun;Sun, Xiao-mei;Chen, Hong
通讯作者：
Chen, Hong
影响因子：
4.6
作者：
Bone NB;Becker EJ Jr;Husain M;Jiang S;Zmijewska AA;Park DW;Chacko B;Darley-Usmar V;Grégoire M;Tadie JM;Thannickal VJ;Zmijewski JW
通讯作者：
Zmijewski JW