科研之友
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摘要
<jats:p> 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<jats:sup>+</jats:sup>/IRAK-M<jats:sup>fl/wt</jats:sup> and control (LysM–Cre<jats:sup>–</jats:sup>/IRAK-M<jats:sup>fl/wt</jats:sup>) 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<jats:sup>+</jats:sup>/IRAK-M<jats:sup>fl/wt</jats:sup> mice compared with control mice. Following PA infection, LysM–Cre<jats:sup>+</jats:sup>/IRAK-M<jats:sup>fl/wt</jats:sup> mice have enhanced lung neutrophilic inflammation, including MPO activity, but reduced PA load. The increased lung MPO activity in LysM–Cre<jats:sup>+</jats:sup>/IRAK-M<jats:sup>fl/wt</jats:sup> 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. </jats:p>
- 出版日期2017-2
