A novel mouse model of conditional IRAK-M deficiency in myeloid cells: application in lung Pseudomonas aeruginosa infection. Issue 2 (February 2017)

• Record Type: Journal Article
• Authors: Jiang, Di; Matsuda, Jennifer; Berman, Reena; Schaefer, Niccolette; Stevenson, Connor; Gross, James; Zhang, Bicheng; Sanchez, Amelia; Li, Liwu; Chu, Hong Wei
• Is Part Of: Innate immunity. Volume 23:Issue 2(2017:Feb.)
• Page Start: 206
• Page End: 215
• Publication Date: 2017-02
• Subjects: IRAK-M -- LysM–Cre -- lung -- infection -- Pseudomonas aeruginosa; Natural immunity -- Periodicals; Endotoxins -- Periodicals; 616.07905
• DOI: 10.1177/1753425916684202
• Languages: English
• ISSNs: 1753-4259

Abstract

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-M fl/wt and control (LysM–Cre – /IRAK-M fl/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-M fl/wt mice compared with control mice. Following PA infection, LysM–Cre + /IRAK-M fl/wt mice have enhanced lung neutrophilic inflammation, including MPO activity, but reduced PA load. The increased lung MPO activity in LysM–Cre + /IRAK-M fl/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.