Albiger Barbara, Dahlberg Sofia, Sandgren Andreas, Wartha Florian, Beiter Katharina, Katsuragi Hiroaki, Akira Shizuo, Normark Staffan, Henriques-Normark Birgitta
Swedish Institute for Infectious Disease Control and Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 18, SE-171 82 Solna, Sweden.
Cell Microbiol. 2007 Mar;9(3):633-44. doi: 10.1111/j.1462-5822.2006.00814.x. Epub 2006 Sep 27.
Toll-like receptor 9 (TLR9) induces an inflammatory response by recognition of unmethylated CpG dinucleotides, mainly present in prokaryotic DNA. So far, TLR9-deficient mice have been shown to be more sensitive than wild-type mice to viral, but not to bacterial infections. Here, we show that mice deficient in TLR9 but not in TLR1, TLR2, TLR4 and TLR6 or IL-1R/IL-18R are more susceptible to a respiratory tract bacterial infection caused by Streptococcus pneumoniae. Intranasal challenge studies revealed that TLR9 plays a protective role in the lungs at an early stage of infection prior to the entry of circulating inflammatory cells. Alveolar as well as bone marrow-derived macrophages deficient in either TLR9 or the myeloid adaptor differentiation protein MyD88 were impaired in pneumococcal uptake and in pneumococcal killing. Our data suggest that in the airways, pneumococcal infection triggers a TLR9 and MyD88-dependent activation of phagocytic activity from resident macrophages leading to an early clearance of bacteria from the lower respiratory tract.
Toll样受体9（TLR9）通过识别主要存在于原核DNA中的未甲基化CpG二核苷酸来诱导炎症反应。到目前为止，已证明TLR9缺陷型小鼠比野生型小鼠对病毒感染更敏感，但对细菌感染不敏感。在此，我们表明，TLR9缺陷但TLR1、TLR2、TLR4和TLR6或IL-1R/IL-18R不缺陷的小鼠更容易受到肺炎链球菌引起的呼吸道细菌感染。鼻内攻击研究表明，在循环炎症细胞进入之前的感染早期，TLR9在肺部发挥保护作用。TLR9或髓样衔接蛋白分化蛋白MyD88缺陷的肺泡巨噬细胞和骨髓来源巨噬细胞在肺炎球菌摄取和肺炎球菌杀伤方面受损。我们的数据表明，在气道中，肺炎球菌感染触发了TLR9和MyD88依赖的驻留巨噬细胞吞噬活性激活，从而导致细菌从下呼吸道早期清除。
