Skerrett Shawn J, Braff Marissa H, Liggitt H Denny, Rubens Craig E
Department of Medicine, University of Washington, Seattle, Washington
Seattle Children's Hospital Research Institute, Seattle, Washington.
Physiol Rep. 2017 Nov;5(21). doi: 10.14814/phy2.13491.
is an important cause of acute bacterial pneumonia. Toll-like receptor 2 (TLR2) recognizes multiple components of the bacterial cell wall and activates innate immune responses to gram-positive bacteria. We hypothesized that TLR2 would have an important role in pulmonary host defense against TLR null (TLR2) mice and wild type (WT) C57BL/6 controls were challenged with aerosolized at a range of inocula for kinetic studies of cytokine and antimicrobial peptide expression, lung inflammation, bacterial killing by alveolar macrophages, and bacterial clearance. Survival was measured after intranasal infection. Pulmonary induction of most pro-inflammatory cytokines was significantly blunted in TLR2 mice 4 and 24 h after infection in comparison with WT controls. Bronchoalveolar concentrations of cathelicidin-related antimicrobial peptide also were reduced in TLR2 mice. Lung inflammation, measured by enumeration of bronchoalveolar neutrophils and scoring of histological sections, was significantly blunted in TLR2 mice. Phagocytosis of by alveolar macrophages in vivo after low-dose infection was unimpaired, but viability of ingested bacteria was significantly greater in TLR2 mice. Bacterial clearance from the lungs was slightly impaired in TLR2 mice after low-dose infection only; bacterial elimination from the lungs was slightly accelerated in the TLR2 mice after high-dose infection. Survival after high-dose intranasal challenge was 50-60% in both groups. TLR2 has a significant role in early innate immune responses to in the lungs but is not required for bacterial clearance and survival from pneumonia.
是急性细菌性肺炎的重要病因。Toll样受体2（TLR2）识别细菌细胞壁的多种成分，并激活对革兰氏阳性菌的先天性免疫反应。我们假设TLR2在肺部宿主防御 中起重要作用，用雾化的 在一系列接种量下对TLR2基因敲除（TLR2）小鼠和野生型（WT）C57BL/6对照进行攻击，以进行细胞因子和抗菌肽表达、肺部炎症、肺泡巨噬细胞杀菌以及细菌清除的动力学研究。鼻内感染后测量存活率。与WT对照相比，感染后4小时和24小时，TLR2小鼠中大多数促炎细胞因子的肺部诱导明显减弱。TLR2小鼠中cathelicidin相关抗菌肽的支气管肺泡浓度也降低。通过支气管肺泡中性粒细胞计数和组织学切片评分来测量的肺部炎症，在TLR2小鼠中明显减弱。低剂量感染后，体内肺泡巨噬细胞对 的吞噬作用未受损，但TLR2小鼠中摄入细菌的存活率明显更高。仅在低剂量感染后TLR2小鼠肺部的细菌清除略有受损；高剂量感染后，TLR2小鼠肺部的细菌清除略有加速。两组高剂量鼻内攻击后的存活率均为50-60%。TLR2在肺部对 的早期先天性免疫反应中起重要作用，但对于 肺炎的细菌清除和存活不是必需的。
