The circulatory small non-coding RNA landscape in community-acquired pneumonia on intensive care unit admission

Hina N Khan, Aldo Jongejan, Lonneke A van Vught, Janneke Horn, Marcus J Schultz, Aeilko H Zwinderman, Olaf L Cremer, Marc J Bonten, Tom van der Poll, Brendon P Scicluna

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Abstract

Community-acquired pneumonia (CAP) is a major cause of sepsis. Despite several clinical trials targeting components of the inflammatory response, no specific treatment other than antimicrobial therapy has been approved. This argued for a deeper understanding of sepsis immunopathology, in particular factors that can modulate the host response. Small non-coding RNA, for example, micro (mi)RNA, have been established as important modifiers of cellular phenotypes. Notably, miRNAs are not exclusive to the intracellular milieu but have also been detected extracellular in the circulation with functional consequences. Here, we sought to determine shifts in circulatory small RNA levels of critically ill patients with CAP-associated sepsis and to determine the influence of clinical severity and causal pathogens on small RNA levels. Blood plasma was collected from 13 critically ill patients with sepsis caused by CAP on intensive care unit admission and from 5 non-infectious control participants. Plasma small RNA-sequencing identified significantly altered levels of primarily mature miRNAs in CAP relative to controls. Pathways analysis of high or low abundance miRNA identified various over-represented cellular biological pathways. Analysis of small RNA levels against common clinical severity and inflammatory parameters indices showed direct and indirect correlations. Additionally, variance of plasma small RNA levels in CAP patients may be explained, at least in part, by differences in causal pathogens. Small nuclear RNA levels were specifically altered in CAP due to Influenza infection in contrast to Streptococcus pneumoniae infection. Pathway analysis of plasma miRNA signatures unique to Influenza or Streptococcus pneumoniae infections showed enrichment for specific proteoglycan, cell cycle, and immunometabolic pathways.

Original languageEnglish
Pages (from-to)7621-7630
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume25
Issue number16
DOIs
Publication statusPublished - Aug 2021

Keywords

  • community-acquired pneumonia
  • micro RNA
  • Sepsis
  • small non-coding RNA
  • Streptococcus pneumoniae

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