Whole transcriptome analysis of high and low IFN-α producers reveals differential response patterns following rhinovirus stimulation.

Autor:	Murray LM; Diamantina Institute The University of Queensland Brisbane QLD Australia., Thillaiyampalam G; Diamantina Institute The University of Queensland Brisbane QLD Australia.; Griffith Institute for Drug Discovery Griffith University Brisbane QLD Australia., Xi Y; Diamantina Institute The University of Queensland Brisbane QLD Australia., Cristino AS; Diamantina Institute The University of Queensland Brisbane QLD Australia.; Griffith Institute for Drug Discovery Griffith University Brisbane QLD Australia., Upham JW; Diamantina Institute The University of Queensland Brisbane QLD Australia.; Respiratory and Sleep Medicine Princess Alexandra Hospital Brisbane QLD Australia.
Jazyk:	angličtina
Zdroj:	Clinical & translational immunology [Clin Transl Immunology] 2021 Nov 17; Vol. 10 (11), pp. e1356. Date of Electronic Publication: 2021 Nov 17 (Print Publication: 2021).
DOI:	10.1002/cti2.1356
Abstrakt:	Objectives: Viral respiratory infections cause considerable morbidity and economic loss. While rhinoviruses (RV) typically cause little more than the common cold, they can produce severe infections and disease exacerbations in susceptible individuals, such as those with asthma. Variations in the regulation of key antiviral cytokines, particularly type I interferon (IFN-α and IFN-β), may contribute to RV susceptibility. To understand this variability, we compared the transcriptomes of high and low type I IFN producers. Methods: Blood mononuclear cells from 238 individuals with or without asthma were cultured in the presence or absence of RV. Those samples demonstrating high or low RV-stimulated IFN-α production (N = 75) underwent RNA-sequencing. Results: Gene expression patterns were similar in samples from healthy participants and those with asthma. At baseline, the high IFN-α producer group showed higher expression of genes associated with plasmacytoid dendritic cells, the innate immune response and vitamin D activation, but lower expression of oxidative stress pathways than the low IFN-α producer group. After RV stimulation, the high IFN-α producer group showed higher expression of genes found in immune response biological pathways and lower expression of genes linked to developmental and catabolic processes when compared to the low IFN-α producer group. Conclusions: These differences suggest that the high IFN-α group has a higher level of immune system readiness, resulting in a more intense and perhaps more focussed pathogen-specific immune response. These results contribute to a better understanding of the variability in type I IFN production between individuals. Competing Interests: JW Upham received an unrestricted grant from AstraZeneca that partially funded this study. Within the last 5 years, he has received personal fees from GSK, Novartis, Sanofi and Boehringer Ingelheim that are unrelated to the submitted work. To the best of our knowledge, the other authors have no conflict of interest, financial or otherwise. (© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Databáze:	MEDLINE
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