Service of Internal Medicine, Infectious Disease Unit, Hospital Universitari Mútua de Terrassa, Plaza Dr Robert 5, 08221 Terrassa, Barcelona, Spain.
Int J Antimicrob Agents. 2010 Feb;35(2):107-13. doi: 10.1016/j.ijantimicag.2009.10.002. Epub 2009 Dec 14.
Pneumococcal pneumonia is characterised by an intense inflammatory response induced mainly by cell wall components of the bacterium. Recognition of cell wall components by Toll-like receptors (TLRs) induces intracellular signalling pathways that culminate in the activation of pro-inflammatory genes through nuclear factor kappaB (NF-kappaB). Tumour necrosis factor-alpha (TNFalpha) is one of the earliest mediators produced and induces a second wave of pro- and anti-inflammatory cytokines that orchestrate the immune response. The magnitude of this response in patients with pneumococcal pneumonia is a complex network and many factors must be considered in the analysis of the cytokine production pattern. First, bacterial growth and the inflammatory response are dynamic processes, produced initially as a local phenomenon with a late systemic extension. Second, host characteristics, such as different cytokine gene polymorphisms, can cause a distinct immune response. Finally, other microorganism determinants and even the immunomodulatory effect of antimicrobials may play a role in cytokine production. Recent data on innate immunity against Streptococcus pneumoniae gathered from the murine model of pneumonia, from studies of human genetic polymorphisms associated with increased susceptibility to pneumococcal infection, and from human clinical trials are discussed. Special emphasis has been placed on the description of the chronology of the complex network of innate immunity triggered by pneumococcal infection.
肺炎链球菌性肺炎的特征是由细菌细胞壁成分引起的强烈炎症反应。Toll 样受体 (TLR) 识别细胞壁成分，诱导细胞内信号通路，最终通过核因子 kappaB (NF-kappaB) 激活促炎基因。肿瘤坏死因子-α (TNFalpha) 是最早产生的介质之一，诱导第二波促炎和抗炎细胞因子，协调免疫反应。肺炎链球菌性肺炎患者中这种反应的程度是一个复杂的网络，在分析细胞因子产生模式时必须考虑许多因素。首先，细菌生长和炎症反应是动态过程，最初作为局部现象产生，后期具有系统扩展。其次，宿主特征，如不同的细胞因子基因多态性，可能导致不同的免疫反应。最后，其他微生物决定因素甚至抗菌药物的免疫调节作用也可能在细胞因子产生中发挥作用。从肺炎的鼠模型、与肺炎链球菌感染易感性增加相关的人类遗传多态性研究以及人类临床试验中收集到的关于固有免疫对抗肺炎链球菌的最新数据进行了讨论。特别强调了描述肺炎链球菌感染引发的固有免疫复杂网络的时间顺序。
