Department of Cell Biology, University of São Paulo, School of Medicine of Ribeirão Preto, FMRP/USP, Ribeirão Preto, SP 14049-900, Brazil.
Microbes Infect. 2010 Oct;12(11):819-27. doi: 10.1016/j.micinf.2010.05.006. Epub 2010 Jun 2.
The intracellular bacterium Legionella pneumophila induces a severe form of pneumonia called Legionnaires diseases, which is characterized by a strong neutrophil (NE) infiltrate to the lungs of infected individuals. Although the participation of pattern recognition receptors, such as Toll-like receptors, was recently demonstrated, there is no information on the role of nod-like receptors (NLRs) for bacterial recognition in vivo and for NE recruitment to the lungs. Here, we employed a murine model of Legionnaires disease to evaluate host and bacterial factors involved in NE recruitment to the mice lungs. We found that L. pneumophila type four secretion system, known as Dot/Icm, was required for NE recruitment as dot/icm mutants fail to trigger NE recruitment in a process independent of bacterial multiplication. By using mice deficient for Nod1, Nod2, and Rip2, we found that these receptors accounted for NE recruitment to the lungs of infected mice. In addition, Rip2-dependent responses were important for cytokine production and bacterial clearance. Collectively, these studies show that Nod1, Nod2, and Rip2 account for generation of innate immune responses in vivo, which are important for NE recruitment and bacterial clearance in a murine model of Legionnaires diseases.
细胞内细菌军团菌会引起一种称为军团病的严重肺炎，其特征是感染个体的肺部有强烈的中性粒细胞 (NE) 浸润。尽管最近已经证明了模式识别受体（如 Toll 样受体）的参与，但对于体内细菌识别和 NE 招募到肺部的核苷酸结合寡聚化结构域样受体 (NLRs) 的作用尚不清楚。在这里，我们使用军团病的小鼠模型来评估宿主和细菌因素在 NE 招募到肺部中的作用。我们发现，军团菌的 IV 型分泌系统，称为 Dot/Icm，是 NE 招募所必需的，因为 dot/icm 突变体不能在不依赖细菌增殖的过程中引发 NE 招募。通过使用缺乏 Nod1、Nod2 和 Rip2 的小鼠，我们发现这些受体负责招募 NE 到感染小鼠的肺部。此外，Rip2 依赖性反应对于细胞因子产生和细菌清除很重要。总之，这些研究表明，Nod1、Nod2 和 Rip2 负责体内固有免疫反应的产生，这对于军团病小鼠模型中的 NE 招募和细菌清除很重要。
