Macrophages are important for the first line of defense against microbial pathogens. Integrin CD11b, which is encoded by Itgam, is expressed on the surface of macrophages and has been implicated in adhesion, migration, and cell-mediated cytotoxicity. However, the functional impact of CD11b on the inflammatory responses of macrophages upon microbial infection remains unclear. Here, we show that CD11b deficiency resulted in increased susceptibility to sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection by enhancing the pro-inflammatory activities of macrophages. Upon infection with MRSA, the mortality of Itgam knockout mice was significantly higher than that of control mice, which is associated with increased production of TNF-α and IL-6. In response to MRSA, both bone marrow-derived macrophages and peritoneal macrophages lacking CD11b produced elevated amounts of pro-inflammatory cytokines and nitric oxide. Moreover, CD11b deficiency upregulated IL-4-induced expression of anti-inflammatory mediators such as IL-10 and arginase-1, and an immunomodulatory function of macrophages to restrain T cell activation. Biochemical and confocal microscopy data revealed that CD11b deficiency augmented the activation of NF-κB signaling and phosphorylation of Akt, which promotes the functional activation of macrophages with pro-inflammatory and immunoregulatory phenotypes, respectively. Overall, our experimental evidence suggests that CD11b is a critical modulator of macrophages in response to microbial infection.

中文翻译：

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CD11b缺乏症通过上调巨噬细胞的炎症反应而加剧了耐甲氧西林的金黄色葡萄球菌诱导的脓毒症。

巨噬细胞对于抵抗微生物病原体的第一道防线很重要。由Itgam编码的整合素CD11b在巨噬细胞表面表达，并与粘附，迁移和细胞介导的细胞毒性有关。但是，CD11b对微生物感染后巨噬细胞的炎症反应的功能影响尚不清楚。在这里，我们表明CD11b缺乏症通过增强巨噬细胞的促炎活性，导致对耐甲氧西林金黄色葡萄球菌（MRSA）感染引起的败血症的敏感性增加。感染MRSA后，Itgam的死亡率基因敲除小鼠显着高于对照小鼠，这与TNF-α和IL-6的产生增加有关。响应MRSA，缺乏CD11b的骨髓来源的巨噬细胞和腹膜巨噬细胞均产生促炎性细胞因子和一氧化氮。此外，CD11b缺乏症上调了IL-4诱导的抗炎介质（如IL-10和精氨酸酶-1）的表达，以及巨噬细胞抑制T细胞活化的免疫调节功能。生化和共聚焦显微镜数据显示，CD11b缺乏增强了NF-κB信号的激活和Akt的磷酸化，分别促进了具有促炎和免疫调节表型的巨噬细胞的功能性激活。全面的，