NLRP3 inflammasome activation in aged macrophages is diminished during Streptococcus pneumoniae infection
NLRP3 inflammasome activation in aged macrophages is diminished during Streptococcus pneumoniae infection
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DOI：
10.1152/ajplung.00393.2017
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发表时间：
2018-03-01
影响因子：
4.9
通讯作者：
Stout-Delgado, Heather W.
中科院分区：
文献类型：
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作者：
Cho, Soo Jung;Rooney, Kristen;Stout-Delgado, Heather W.
肺炎球菌感染是美国第八大死因，据估计，老年患者（>= 65 岁）是最严重的病例。我们当前研究的目的是了解生物衰老对肺炎链球菌（细菌性肺炎的病原体）的先天免疫反应的影响。通过使用体外和体内衰老小鼠模型，我们的研究结果表明，年龄增强的未折叠蛋白反应（UPR）有助于减少肺炎链球菌感染期间炎症小体的组装和激活。用内质网伴侣和减压剂牛磺熊去氧胆酸 (TUDCA) 预处理老年小鼠可降低老年宿主的死亡率，这与 NLRP3 炎性体激活增加、病原体清除率提高和感染期间肺炎减少有关。总而言之，我们的数据提供了关于为什么老年人更容易感染肺炎链球菌的新证据，并为降低该人群的发病率和死亡率提供了可能的治疗目标。
Pneumococcal infections are the eigth leading cause of death in the United States, and it is estimated that older patients (>= 65 yr of age) account for the most serious cases. The goal of our current study is to understand the impact of biological aging on innate immune responses to Streptococcus pneumoniae, a causative agent of bacterial pneumonia. With the use of in vitro and in vivo aged murine models, our findings demonstrate that ageenhanced unfolded protein responses (UPRs) contribute to diminished inflammasome assembly and activation during S. pneumoniae infection. Pretreatment of aged mice with endoplasmic reticulum chaperone and the stress-reducing agent tauroursodeoxycholic acid (TUDCA) decreased mortality in aged hosts that was associated with increased NLRP3 inflammasome activation, improved pathogen clearance, and decreased pneumonitis during infection. Taken together, our data provide new evidence as to why older persons are more susceptible to S. pneumoniae and provide a possible therapeutic target to decrease morbidity and mortality in this population.