A novel mouse model of conditional IRAK-M deficiency in myeloid cells: application in lung Pseudomonas aeruginosa infection.
A novel mouse model of conditional IRAK-M deficiency in myeloid cells: application in lung Pseudomonas aeruginosa infection.
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DOI：
10.1177/1753425916684202
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发表时间：
2017-03
期刊：
影响因子：
3.2
通讯作者：
Chu HW
中科院分区：
文献类型：
--
作者：
Jiang D;Matsuda J;Berman R;Schaefer N;Stevenson C;Gross J;Zhang B;Sanchez A;Li L;Chu HW
巨噬细胞等髓系细胞对抵抗感染的先天防御至关重要。IL-1受体相关激酶M(IRAK-M)是细菌感染过程中TLR信号的负调控因子，但髓系细胞IRAK-M在细菌感染中的作用尚不清楚。我们的目标是建立一种新的条件基因敲除小鼠模型，以确定髓系细胞IRAK-M在细菌感染中的作用。将IRAK-M基因敲除小鼠与LysM-Cre基因敲除小鼠杂交，得到髓系细胞特异性的IRAK-M基因敲除小鼠。将得到的LysM-Cre+/IRAK-mfl/wt小鼠和对照(LysM-Cre−/IRAK-mfl/wt)小鼠鼻内感染铜绿假单胞菌(PA)。检测白细胞、支气管肺泡灌洗液(BAL)液和肺组织中IRAK-M缺失、炎症反应、髓过氧化物酶(MPO)活性和PA负荷。用BAL液进行PA杀伤实验，以确定IRAK-M介导的宿主防御机制。与对照组相比，LysM-Cre+/IRAK-MFL/wt组小鼠肺泡巨噬细胞和肺巨噬细胞中IRAK-M的mRNA和蛋白水平显著降低。PA感染后，LysM-Cre+/IRAK-MFL/wt小鼠肺中性粒细胞炎症增强，包括MPO活性，但PA负荷降低。在LysM-Cre+/IRAK-MFL/wt小鼠BAL液中肺MPO活性增加，降低了PA负荷。IRAK-M条件性基因敲除小鼠的产生将使研究人员能够准确地确定IRAK-M在感染和炎症期间在髓系细胞和其他类型细胞中的功能。
Myeloid cells such as macrophages are critical to innate defense against infection. IL-1 receptor-associated kinase M (IRAK-M) is a negative regulator of TLR signaling during bacterial infection, but the role of myeloid cell IRAK-M in bacterial infection is unclear. Our goal was to generate a novel conditional knockout mouse model to define the role of myeloid cell IRAK-M during bacterial infection. Myeloid cell-specific IRAK-M knockout mice were generated by crossing IRAK-M floxed mice with LysM–Cre knock-in mice. The resulting LysM–Cre+/IRAK-Mfl/wt and control (LysM–Cre−/IRAK-Mfl/wt) mice were intranasally infected with Pseudomonas aeruginosa (PA). IRAK-M deletion, inflammation, myeloperoxidase (MPO) activity and PA load were measured in leukocytes, bronchoalveolar lavage (BAL) fluid and lungs. PA killing assay with BAL fluid was performed to determine mechanisms of IRAK-M-mediated host defense. IRAK-M mRNA and protein levels in alveolar and lung macrophages were significantly reduced in LysM–Cre+/IRAK-Mfl/wt mice compared with control mice. Following PA infection, LysM–Cre+/IRAK-Mfl/wt mice have enhanced lung neutrophilic inflammation, including MPO activity, but reduced PA load. The increased lung MPO activity in LysM–Cre+/IRAK-Mfl/wt mouse BAL fluid reduced PA load. Generation of IRAK-M conditional knockout mice will enable investigators to determine precisely the function of IRAK-M in myeloid cells and other types of cells during infection and inflammation.
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DOI：
10.2147/copd.s15417
发表时间：
2011
影响因子：
2.8
作者：
Moghaddam SJ;Ochoa CE;Sethi S;Dickey BF
通讯作者：
Dickey BF
影响因子：
6
作者：
Chu, HW;Balzar, S;Wenzel, SE
通讯作者：
Wenzel, SE
DOI：
10.1164/rccm.200207-728oc
发表时间：
2003-02-15
影响因子：
24.7
作者：
King, PT;Hutchinson, PE;Holdsworth, SR
通讯作者：
Holdsworth, SR
影响因子：
4
作者：
Traves SL;Proud D
通讯作者：
Proud D
mRNA 表达如何预测蛋白质表达？
影响因子：
3.7
作者：
Guo, Yanfang;Xiao, Peng;Deng, Hongwen
通讯作者：
Deng, Hongwen