Genomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.

TitleGenomic Circuitry Underlying Immunological Response to Pediatric Acute Respiratory Infection.
Publication TypeJournal Article
Year of Publication2018
AuthorsHenrickson SE, Manne S, Dolfi DV, Mansfield KD, Parkhouse K, Mistry RD, Alpern ER, Hensley SE, Sullivan KE, Coffin SE, E Wherry J
JournalCell Rep
Volume22
Issue2
Pagination411-426
Date Published2018 Jan 09
ISSN2211-1247
Abstract

Acute respiratory tract viral infections (ARTIs) cause significant morbidity and mortality. CD8 T cells are fundamental to host responses, but transcriptional alterations underlying anti-viral mechanisms and links to clinical characteristics remain unclear. CD8 T cell transcriptional circuitry in acutely ill pediatric patients with influenza-like illness was distinct for different viral pathogens. Although changes included expected upregulation of interferon-stimulated genes (ISGs), transcriptional downregulation was prominent upon exposure to innate immune signals in early IFV infection. Network analysis linked changes to severity of infection, asthma, sex, and age. An influenza pediatric signature (IPS) distinguished acute influenza from other ARTIs and outperformed other influenza prediction gene lists. The IPS allowed a deeper investigation of the connection between transcriptional alterations and clinical characteristics of acute illness, including age-based differences in circuits connecting the STAT1/2 pathway to ISGs. A CD8 T cell-focused systems immunology approach in pediatrics identified age-based alterations in ARTI host response pathways.

DOI10.1016/j.celrep.2017.12.043
Alternate JournalCell Rep
PubMed ID29320737