Sepsis is a dysregulated immune response to infections that frequently precipitates multiple organ dysfunction and death despite intensive supportive therapy. The aim of the present study was to identify sepsis-induced alterations in the signaling transcriptome of peripheral blood leukocytes that might shed light on the elusive transition from proinflammatory to anti-inflammatory responses and underlie long-term post-sepsis immunosuppression.

Peripheral blood leukocytes were collected from subjects (i) with systemic inflammation, (ii) with sepsis in the acute phase and (iii) 6 months after recovery from sepsis, corresponding to progressive stages of the disease. Transcriptomic analysis was performed with the QuantStudio 12K Flex OpenArray Human Signal Transduction Panel analyzing transcripts of 573 genes playing a significant role in signaling. Of them, 145 genes exhibited differential expression in sepsis as compared to systemic inflammation. Pathway analysis revealed enhanced expression levels of genes involved in primary immune responses (proinflammatory cytokines, neutrophil and macrophage activation markers) and signatures characteristic of immunosuppression (increased expression of anti-inflammatory cytokines and proapoptotic genes; diminished expression of T and B cell receptor dependent activating and survival pathways).

Importantly, sepsis-induced expression patterns of 39 genes were not normalized by the end of the 6-month follow-up period, indicating expression aberrations persisting long after clinical recovery. Functional analysis of these transcripts revealed downregulation of the antiapoptotic Wnt and mTOR signaling pathways that might explain the post-sepsis immunosuppression commonly seen in sepsis survivors.

脓毒症是一种对感染的免疫反应失调，尽管进行了强化支持治疗，但仍经常导致多器官功能障碍和死亡。本研究的目的是确定脓毒症引起的外周血白细胞信号转录组的改变，这可能揭示从促炎反应到抗炎反应的难以捉摸的转变，并成为脓毒症后长期免疫抑制的基础。

外周血白细胞采集自以下受试者：(i) 患有全身性炎症，(ii) 患有急性期脓毒症，以及 (iii) 脓毒症恢复后 6 个月（对应于疾病的进展阶段）。使用 QuantStudio 12K Flex OpenArray 人类信号转导面板进行转录组分析，分析在信号传导中发挥重要作用的 573 个基因的转录本。其中，145 个基因在脓毒症中与全身炎症相比表现出差异表达。通路分析揭示了参与初级免疫反应的基因表达水平增强（促炎细胞因子、中性粒细胞和巨噬细胞激活标记物）和免疫抑制特征特征（抗炎细胞因子和促凋亡基因的表达增加；T 细胞和 B 细胞受体依赖性激活的表达减少）和生存途径）。

重要的是，脓毒症诱导的 39 个基因的表达模式在 6 个月的随访期结束时并未正常化，表明表达异常在临床恢复后仍持续很长时间。这些转录本的功能分析揭示了抗凋亡 Wnt 和 mTOR 信号通路的下调，这可能解释了脓毒症幸存者中常见的脓毒症后免疫抑制。