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Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life
journal contribution
posted on 2023-02-10, 04:57 authored by JF Read, M Serralha, D Mok, B Holt, M Cruickshank, YV Karpievitch, DI Broadhurst, Peter Sly, DH Strickland, SN Reinke, PG Holt, A BoscoAppropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group. Employing a systems biology approach to analysis of multi-omic profiles generated from a high-risk cohort (n=50), we found that the intensity of activation of an LPS-induced interferon gene network at birth was predictive of sLRI risk in infancy (AUC=0.724). Connectivity patterns within this network were stronger among susceptible individuals, and a systems biology approach identified IRF1 as a putative master regulator of this response. These findings were specific to the LPS-induced interferon response and were not observed following activation of viral nucleic acid sensing pathways. Comparison of responses at birth versus age 5 demonstrated that LPS-induced interferon responses but not responses triggered by viral nucleic acid sensing pathways may be subject to strong developmental regulation. These data suggest that the risk of sLRI in early life is in part already determined at birth, and additionally that the developmental status of LPS-induced interferon responses may be a key determinant of susceptibility. Our findings provide a rationale for the identification of at-risk infants for early intervention aimed at sLRI prevention and identifies targets which may be relevant for drug development.
History
Journal
Frontiers in ImmunologyVolume
13Pagination
876654-Location
SwitzerlandPublisher DOI
ISSN
1664-3224eISSN
1664-3224Language
engPublication classification
C1 Refereed article in a scholarly journalPublisher
Frontiers Media SAUsage metrics
Keywords
innate immunityinterferonlipopolysaccharide (LPS)multi-omicspathogen recognition receptor (PRR)respiratory infectionsystems biologyAntiviral AgentsAsthmaChild, PreschoolHumansInfantInfant, NewbornInterferonsLipopolysaccharidesNucleic AcidsRespiratory Tract InfectionsPreventionInfectious DiseasesClinical ResearchGeneticsLungPediatric2.1 Biological and endogenous factors2.2 Factors relating to the physical environment2 AetiologyInfection3 Good Health and Well BeingImmunologyMedical Microbiology not elsewhere classified
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