Background. Therapeutic strategies to modulate the host response to bacterial pneumonia are needed to improve outcomes during community-acquired pneumonia. This study used mice with impaired Fas signalling to examine susceptibility to pneumococcal pneumonia and decoy receptor 3 analogue (DcR3-a) to correct factors associated with increased susceptibility.ududMethods. Wild-type mice and those with varying degrees of impairment of Fas (lpr) or Fas ligand signalling (gld) were challenged with Streptococcus pneumoniae and microbiological and immunological outcomes measured in the presence or absence of DcR3-a.ududResults. During established pneumonia, neutrophils became the predominant cell in the airway and gld mice were less able to clear bacteria from the lungs, demonstrating localised impairment of pulmonary neutrophil function in comparison to lpr or wild-type mice. T-cells from gld mice had enhanced activation and reduced apoptosis in comparison to wild-type and lpr mice during established pneumonia. Treatment with DcR3-a reduced T-cell activation and corrected the defect in pulmonary bacterial clearance in gld mice.ududConclusions. The results suggest that imbalance in tumour necrosis factor superfamily signalling and excessive T-cell activation can impair bacterial clearance in the lung but that DcR3-a treatment can reduce T-cell activation, restore optimal pulmonary neutrophil function and enhance bacterial clearance during S pneumoniae infection.
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机译:背景。需要调节宿主对细菌性肺炎反应的治疗策略,以改善社区获得性肺炎的预后。这项研究使用Fas信号受损的小鼠检查对肺炎球菌性肺炎和诱饵受体3类似物(DcR3-a)的敏感性,以纠正与敏感性增加相关的因素。 ud ud方法。用肺炎链球菌攻击野生型小鼠和Fas(lpr)或Fas配体信号转导(gld)程度不同的小鼠,并在存在或不存在DcR3-a的情况下测量其微生物学和免疫学结果。 ud ud结果。在确立的肺炎期间,中性粒细胞成为气道中的主要细胞,与lpr或野生型小鼠相比,gld小鼠从肺中清除细菌的能力较弱,这表明肺中性粒细胞功能的局部损伤。在确定的肺炎期间,与野生型和lpr小鼠相比,来自gld小鼠的T细胞具有增强的活化作用和减少的细胞凋亡。 DcR3-a处理减少了gld小鼠的T细胞活化并纠正了肺细菌清除的缺陷。 ud ud结论。结果表明,肿瘤坏死因子超家族信号的失衡和过度的T细胞活化可损害肺中的细菌清除,但DcR3-a治疗可减少T细胞活化,恢复最佳的肺中性粒细胞功能并增强肺炎链球菌感染期间的细菌清除。 。
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