Arsanis Biosciences, Helmut-Qualtinger-Gasse 2, Campus Vienna Biocenter, 1030 Vienna, Austria.
Arsanis Biosciences, Helmut-Qualtinger-Gasse 2, Campus Vienna Biocenter, 1030 Vienna, Austria.
Cytokine. 2018 Nov;111:389-397. doi: 10.1016/j.cyto.2018.09.012. Epub 2018 Nov 18.
Streptococcuspneumoniae is a major human pathogen at the extremes of age. The elderly are particularly vulnerable to S.pneumoniae, the most common causative agent of bacterial pneumonia in this population. Despite the availability of vaccines and antibiotics, mortality rates associated with pneumococcal pneumonia in this age group remain high. In light of globally increasing life-expectancy, a better understanding of the patho-mechanisms of elderly pneumococcal pneumonia, including alterations in innate immune responses, is needed to develop improved therapies. In this study we aimed at investigating how increased susceptibility to pneumococcal infection relates to inflammation kinetics in the aged mouse pneumonia model by determining pulmonary cytokine and chemokine levels and comparing these parameters to those measured in young adult mice. Firstly, we detected overall higher pulmonary cytokine and chemokine levels in aged mice. However, upon induction of pneumococcal pneumonia in aged mice, delayed production of certain analytes, such as IFN-γ, MIG (CXCL9), IP-10 (CXCL10), MCP-1 (CCL2), TARC (CCL17) and MDC (CCL22) became apparent. In addition, aged mice were unable to control excess inflammatory responses: while young mice showed peak inflammatory responses at 20 h and subsequent resolution by 48 h post intranasal challenge, in aged mice increasing cytokine and chemokine levels were measured. These findings highlight the importance of considering multiple time points when delineating inflammatory responses to S.pneumoniae in an age-related context. Finally, correlation between pulmonary bacterial burden and cytokine or chemokine levels in young mice suggested that appropriately controlled inflammatory responses support the host to fight pneumococcal infection.
肺炎链球菌是年龄处于极值人群的主要人类病原体。老年人尤其容易受到肺炎链球菌的影响，肺炎链球菌是该人群细菌性肺炎的最常见病原体。尽管有疫苗和抗生素可用，但该年龄段与肺炎球菌性肺炎相关的死亡率仍然很高。鉴于全球预期寿命的增加，需要更好地了解老年人肺炎链球菌性肺炎的病理机制，包括先天免疫反应的改变，以开发更好的治疗方法。在这项研究中，我们旨在通过确定肺部细胞因子和趋化因子水平，并将这些参数与年轻成年小鼠的参数进行比较，来研究肺炎链球菌感染易感性增加与老年小鼠肺炎模型中炎症动力学的关系。首先，我们检测到老年小鼠的肺部细胞因子和趋化因子水平总体较高。然而，在老年小鼠中诱导肺炎链球菌性肺炎后，某些分析物（如 IFN-γ、MIG（CXCL9）、IP-10（CXCL10）、MCP-1（CCL2）、TARC（CCL17）和 MDC（CCL22））的产生延迟。此外，老年小鼠无法控制过度的炎症反应：年轻小鼠在鼻内挑战后 20 小时达到炎症反应高峰，随后在 48 小时内缓解，而老年小鼠的细胞因子和趋化因子水平不断增加。这些发现强调了在年龄相关背景下描绘肺炎链球菌炎症反应时考虑多个时间点的重要性。最后，年轻小鼠肺部细菌负荷与细胞因子或趋化因子水平之间的相关性表明，适当控制的炎症反应支持宿主抵抗肺炎链球菌感染。
