文章基本信息

标题：Sex disparities in influenza: A multiscale network analysis
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作者：Chang Wang ; Lauren P. Lashua ; Chalise E. Carter 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2022
卷号：25
期号：5
页码：1-20
DOI：10.1016/j.isci.2022.104192
语种：English
出版社：Elsevier
摘要：SummarySex differences in the pathogenesis of infectious diseases because of differential immune responses between females and males have been well-documented for multiple pathogens. However, the molecular mechanism underlying the observed sex differences in influenza virus infection remains poorly understood. In this study, we used a network-based approach to characterize the blood transcriptome collected over the course of infection with influenza A virus from female and male ferrets to dissect sex-biased gene expression. We identified significant differences in the temporal dynamics and regulation of immune responses between females and males. Our results elucidate sex-differentiated pathways involved in the unfolded protein response (UPR), lipid metabolism, and inflammatory responses, including a female-biased IRE1/XBP1 activation and male-biased crosstalk between metabolic reprogramming and IL-1 and AP-1 pathways. Overall, our study provides molecular insights into sex differences in transcriptional regulation of immune responses and contributes to a better understanding of sex biases in influenza pathogenesis.Graphical abstractDisplay OmittedHighlights•Regulation of immune responses between females and males is significantly different•Rapid activation of UPR in females triggers potent immune and inflammatory responses•Male-specific regulatory pattern in the AP1 pathway indicate a bias in immune responseBiological sciences; Immunology; Virology; Systems biology