Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life.

Autor:	Read JF; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.; School of Medicine, The University of Western Australia, Nedlands, WA, Australia., Serralha M; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia., Mok D; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia., Holt BJ; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia., Cruickshank M; School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia., Karpievitch YV; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.; School of Biomedical Sciences, The University of Western Australia, Nedlands, WA, Australia., Broadhurst DI; Centre for Integrative Metabolomics & Computational Biology, School of Science, Edith Cowan University, Joondalup, WA, Australia., Sly PD; Child Health Research Centre, The University of Queensland, Brisbane, QLD, Australia., Strickland DH; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.; The University of Western Australia Centre for Child Health Research, The University of Western Australia, Nedlands, WA, Australia., Reinke SN; Centre for Integrative Metabolomics & Computational Biology, School of Science, Edith Cowan University, Joondalup, WA, Australia., Holt PG; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.; The University of Western Australia Centre for Child Health Research, The University of Western Australia, Nedlands, WA, Australia., Bosco A; Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia.; The University of Western Australia Centre for Child Health Research, The University of Western Australia, Nedlands, WA, Australia.; Asthma and Airway Disease Research Center, University of Arizona, Tucson, AZ, United States.; Department of Immunobiology, The University of Arizona College of Medicine, Tucson, AZ, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Aug 05; Vol. 13, pp. 876654. Date of Electronic Publication: 2022 Aug 05 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.876654
Abstrakt:	Appropriate 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. Competing Interests: JFR and AB are co-inventors on a provisional patent filed subsequent to this work. JFR and AB are co-founders, equity holders, and directors of a startup company Respiradigm Pty Ltd related to this provisional patent. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Read, Serralha, Mok, Holt, Cruickshank, Karpievitch, Broadhurst, Sly, Strickland, Reinke, Holt and Bosco.)
Databáze:	MEDLINE
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