Single cell transcriptomics identifies distinct profiles in pediatric acute respiratory distress syndrome.
Tim FlerlageJeremy Chase CrawfordEmma Kaitlynn AllenDanielle SevernsShaoyuan TanSherri SurmanGranger RidoutTanya NovakAdrienne G RandolphAlina N WestPaul Glyndwr ThomasPublished in: Nature communications (2023)
Acute respiratory distress syndrome (ARDS), termed pediatric ARDS (pARDS) in children, is a severe form of acute respiratory failure (ARF). Pathologic immune responses are implicated in pARDS pathogenesis. Here, we present a description of microbial sequencing and single cell gene expression in tracheal aspirates (TAs) obtained longitudinally from infants with ARF. We show reduced interferon stimulated gene (ISG) expression, altered mononuclear phagocyte (MNP) transcriptional programs, and progressive airway neutrophilia associated with unique transcriptional profiles in patients with moderate to severe pARDS compared to those with no or mild pARDS. We additionally show that an innate immune cell product, Folate Receptor 3 (FOLR3), is enriched in moderate or severe pARDS. Our findings demonstrate distinct inflammatory responses in pARDS that are dependent upon etiology and severity and specifically implicate reduced ISG expression, altered macrophage repair-associated transcriptional programs, and accumulation of aged neutrophils in the pathogenesis of moderate to severe pARDS caused by RSV.
Keyphrases
- acute respiratory distress syndrome
- extracorporeal membrane oxygenation
- respiratory failure
- mechanical ventilation
- single cell
- gene expression
- immune response
- early onset
- rna seq
- poor prognosis
- drug induced
- dna methylation
- public health
- intensive care unit
- high intensity
- multiple sclerosis
- genome wide
- dendritic cells
- binding protein
- adipose tissue
- peripheral blood
- inflammatory response
- liver failure
- lymph node
- microbial community
- long non coding rna
- aortic dissection
- heat stress
- respiratory tract
- heat shock protein