Sex disparities in influenza: A multiscale network analysis
iScience
; 25(5), 2022.
Article
in English
| EuropePMC | ID: covidwho-1812512
ABSTRACT
Summary Sex 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 Highlights • 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 response Biological sciences;Immunology;Virology;Systems biology
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Collection:
Databases of international organizations
Database:
EuropePMC
Language:
English
Journal:
IScience
Year:
2022
Document Type:
Article
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