mRNA-miRNA integration analysis of T-cell exhaustion in sepsis from community-acquired pneumonia.

Aim: 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. Methods: 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). Results: 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 Conclusion: 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.