Carl D. Britto (United States of America)
Boston Children's Hospital PediatricsPresenter of 1 Presentation
AN ANALYSIS OF IN-VIVO HOST AND PATHOGEN TRANSCRIPTOMIC SIGNATURES ASSOCIATED WITH SEVERE OUTCOMES IN PEDIATRIC INFLUENZA-STAPHYLOCOCCUS AUREUS PNEUMONIA (ID 655)
Abstract
Background
S.aureus pneumonia complicating influenza infection is an important cause of PICU related child-mortality. Delineating pathogen-related and host immune predictors of severe outcomes will aid in prioritising targeted interventions and indentifying at-risk children.
Methods
mRNA was extracted from endotracheal aspirates from 34 previously healthy children requiring intubation for influenza infection. Ten each had confirmed respiratory coinfection with MRSA and MSSA, and 14 children with influenza alone served as controls. mRNA expression of 200 S.aureus and 600 human immune genes were analysed to identify relevant gene signatures and pathways associated with survival and death/prolonged multiple organ dysfunction syndrome (pMODS).
Results
More host genes were differentially expressed in the MRSA group than in the MSSA group. Down-regulation of host genes such as CXCL10 and CXCL11 were associated with death/pMODS (Figure1). Forty-four significant genes in the MRSA group and 17 genes in the MSSA group satisfied criteria for biological plausibility and were involved in programmed cell death, complement, cytokine signalling and expression of C-type lecithin receptors. Among those infected with S.aureus in the died/pMODS group [n=10] 65 significant genes met biological criteria while 16 genes met similar criteria in the group who survived [n=10]. Interferon-alpha, -beta and -gamma as well as interleukin signalling – IL-1, -36, -38, -10, -4, -13, -21 were the most significant pathways down-regulated in the died/pMODS group. Upregulation of interleukin signalling – IL-6, -10, -27, -4,-13 were the most significant pathways in the survivors. The mecA gene was the only significantly differentially expressed pathogen gene between MRSA and MSSA groups.
Conclusions
Early in the course of severe influenza-S.aureus pneumonia, airway host gene expression profiles delineate adverse outcomes, unlike pathogen genes. Innate immune pathways, involving CXCL10 and CXCL11, drive host responses that may impact outcome.
Clinical Trial Registration
Clinical trial registration: N/A