Center for Infection and Immunity Amsterdam, University of Amsterdam, The Netherlands.
J Infect Dis. 2012 Jun 15;205(12):1849-57. doi: 10.1093/infdis/jis290. Epub 2012 Apr 5.
Streptococcus pneumoniae is the most common causative organism in community-acquired pneumonia. Pneumococci that try to invade the lower airways are recognized by innate immune cells through pattern recognition receptors, including Toll-like receptors 2, 4, and 9. Interleukin 1 (IL-1) receptor-associated kinase (IRAK)-M is a proximal inhibitor of Toll-like receptor signaling.
To determine the role of IRAK-M in host defense during pneumococcal pneumonia, IRAK-M- deficient and wild-type mice were intranasally infected with S. pneumoniae.
IRAK-M-deficient mice demonstrated a reduced lethality after infection with S. pneumoniae via the airways. Whereas bacterial burdens were similar in IRAK-M-deficient and wild-type mice early (3 hours) after infection, from 24 hours onward the number of pneumococci recovered from lungs and distant body sites were 10-100-fold lower in the former mouse strain. The diminished bacterial growth and dissemination in IRAK-M-deficient mice were preceded by an increased early influx of neutrophils into lung tissue and elevated pulmonary levels of IL-1β and CXCL1. IRAK-M deficiency did not influence bacterial growth after intravenous administration of S. pneumoniae.
These data suggest that IRAK-M impairs host defense during pneumococcal pneumonia at the primary site of infection at least in part by inhibiting the early immune response.
肺炎链球菌是社区获得性肺炎最常见的病原体。试图侵袭下呼吸道的肺炎球菌通过模式识别受体（包括 Toll 样受体 2、4 和 9）被先天免疫细胞识别。白细胞介素 1（IL-1）受体相关激酶（IRAK）-M 是 Toll 样受体信号的近端抑制剂。
为了确定 IRAK-M 在肺炎球菌性肺炎宿主防御中的作用，通过鼻腔感染使 IRAK-M 缺陷型和野生型小鼠感染肺炎链球菌。
经气道感染肺炎链球菌后，IRAK-M 缺陷型小鼠的致死率降低。虽然 IRAK-M 缺陷型和野生型小鼠在感染后 3 小时（早期）细菌负荷相似，但从 24 小时开始，从肺部和远处身体部位回收的肺炎球菌数量前者小鼠株低 10-100 倍。IRAK-M 缺陷型小鼠中细菌生长和扩散减少之前，早期有更多中性粒细胞涌入肺组织，并且肺内的白细胞介素 1β（IL-1β）和 CXCL1 水平升高。IRAK-M 缺陷不影响肺炎链球菌静脉注射后的细菌生长。
这些数据表明，IRAK-M 通过抑制早期免疫反应，至少部分地削弱了肺炎球菌性肺炎感染部位的宿主防御。
