Oda Sayaka, Matsumoto Hisatake, Togami Yuki, Yoshimura Jumpei, Ito Hiroshi, Onishi Shinya, Muratsu Arisa, Mitsuyama Yumi, Okuzaki Daisuke, Ogura Hiroshi, Tanaka Susumu, Oda Jun
Department of Oral and Maxillofacial Surgery Osaka University Graduate School of Dentistry Osaka Japan.
Department of Traumatology and Acute Critical Medicine Osaka University Graduate School of Medicine Osaka Japan.
Acute Med Surg. 2025 Apr 2;12(1):e70054. doi: 10.1002/ams2.70054. eCollection 2025 Jan-Dec.
Community-acquired pneumonia is an acute lung infection in patients without recent healthcare exposure that can progress to severe sepsis. Despite the well-established influence of miRNAs on inflammation, their specific roles in pneumonia-associated sepsis remain underexplored. In this pilot study, we aimed to provide insights into the pathogenesis of community-acquired pneumonia-associated sepsis by performing an integrative mRNA-miRNA analysis to identify key cellular signaling pathways and potential molecular targets for future research and treatment development.
We conducted a prospective, observational, single-center study including 14 critically ill patients with community-acquired pneumonia-associated sepsis and 15 healthy controls (median age: 78 [interquartile range 67.3-83.5] and 55 [interquartile range 40.5-59.0] years, respectively).
Eleven patients required ventilatory support, and six met the diagnostic criteria for septic shock. All patients survived. RNA sequencing revealed 1209 upregulated and 1461 downregulated differentially expressed genes for mRNAs (false discovery rate < 0.05, |log fold change| >1.2), 51 upregulated and 21 downregulated genes for miRNAs, and 646 upregulated and 1274 downregulated for mRNA related to miRNAs. Canonical pathway analysis revealed activation of the programmed death-1/programmed death-ligand-1 cancer immunotherapy pathway and suppression of the Th1 pathway, indicating T-cell exhaustion in the acute phase of community-acquired pneumonia-associated sepsis.
This study provides valuable insights into the molecular mechanisms underlying CAP-associated sepsis, confirming the occurrence of immune dysregulation, particularly T-cell exhaustion. Our findings suggest that specific miRNAs and signaling pathways identified here may serve as potential therapeutic targets or biomarkers.
社区获得性肺炎是一种发生在近期无医疗接触史患者的急性肺部感染，可进展为严重脓毒症。尽管微小RNA（miRNA）对炎症的影响已得到充分证实，但其在肺炎相关脓毒症中的具体作用仍未得到充分研究。在这项初步研究中，我们旨在通过进行整合的mRNA-miRNA分析，以确定关键的细胞信号通路和潜在的分子靶点，为未来的研究和治疗开发提供对社区获得性肺炎相关脓毒症发病机制的见解。
我们进行了一项前瞻性、观察性、单中心研究，纳入了14例患有社区获得性肺炎相关脓毒症的危重症患者和15名健康对照（中位年龄分别为78岁[四分位间距67.3 - 83.5]和55岁[四分位间距40.5 - 59.0]）。
11例患者需要通气支持，6例符合感染性休克的诊断标准。所有患者均存活。RNA测序显示，mRNA有1209个上调和1461个下调的差异表达基因（错误发现率<0.05，|log倍数变化|>1.2），miRNA有51个上调和21个下调基因，以及与miRNA相关的mRNA有646个上调和1274个下调。典型通路分析显示程序性死亡-1/程序性死亡配体-1癌症免疫治疗通路激活以及Th1通路受抑制，表明在社区获得性肺炎相关脓毒症急性期存在T细胞耗竭。
本研究为社区获得性肺炎相关脓毒症的分子机制提供了有价值的见解，证实了免疫失调的发生，尤其是T细胞耗竭。我们的研究结果表明，此处鉴定出的特定miRNA和信号通路可能作为潜在的治疗靶点或生物标志物。
