Hommes Tijmen J, Hoogendijk Arie J, Dessing Mark C, Van't Veer Cornelis, Florquin Sandrine, de Vos Alex F, van der Poll Tom
1Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 2Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 3Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 4Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Crit Care Med. 2014 Dec;42(12):e783-90. doi: 10.1097/CCM.0000000000000686.
Streptococcus pneumoniae is the most common causative organism in community-acquired pneumonia responsible for millions of deaths every year. DNAX-activating protein of 12 kDa is an adaptor molecule for different myeloid expressed receptors involved in innate immunity.
Animal study.
University research laboratory.
DNAX-activating protein of 12 kDa-deficient (dap12) and wild-type mice.
Mice were intranasally infected with S. pneumoniae. In addition, ex vivo responsiveness of alveolar macrophages was examined.
dap12 alveolar macrophages released more tumor necrosis factor-α upon stimulation with S. pneumoniae and displayed increased phagocytosis of this pathogen compared with wild-type cells. After infection with S. pneumoniae via the airways, dap12 mice demonstrated reduced bacterial outgrowth in the lungs together with delayed dissemination to distant body sites relative to wild-type mice. This favorable response in dap12 mice was accompanied by reduced lung inflammation and an improved survival.
These data suggest that DNAX-activating protein of 12 kDa impairs host defense during pneumococcal pneumonia at the primary site of infection at least in part by inhibiting phagocytosis by alveolar macrophages.
肺炎链球菌是社区获得性肺炎最常见的病原体，每年导致数百万例死亡。12 kDa的DNAX激活蛋白是参与固有免疫的不同髓系表达受体的衔接分子。
动物研究。
大学研究实验室。
12 kDa的DNAX激活蛋白缺陷（dap12）小鼠和野生型小鼠。
小鼠经鼻内感染肺炎链球菌。此外，检测了肺泡巨噬细胞的体外反应性。
与野生型细胞相比，dap12肺泡巨噬细胞在用肺炎链球菌刺激后释放更多的肿瘤坏死因子-α，并且对该病原体的吞噬作用增强。经气道感染肺炎链球菌后，与野生型小鼠相比，dap12小鼠肺部细菌生长减少，且向远处身体部位的播散延迟。dap12小鼠的这种良好反应伴随着肺部炎症减轻和存活率提高。
这些数据表明，12 kDa的DNAX激活蛋白至少部分通过抑制肺泡巨噬细胞的吞噬作用，在肺炎链球菌肺炎感染的原发部位损害宿主防御。
