Wang Chang, Lashua Lauren P, Carter Chalise E, Johnson Scott K, Wang Minghui, Ross Ted M, Ghedin Elodie, Zhang Bin, Forst Christian V
Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
Center for Vaccines and Immunology, University of Georgia, Athens, GA 30602, USA.
iScience. 2022 Apr 1;25(5):104192. doi: 10.1016/j.isci.2022.104192. eCollection 2022 May 20.
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.
由于雌性和雄性之间免疫反应不同，多种病原体感染发病机制中的性别差异已有充分记录。然而，流感病毒感染中所观察到的性别差异背后的分子机制仍知之甚少。在本研究中，我们使用基于网络的方法来表征雌性和雄性雪貂感染甲型流感病毒过程中收集的血液转录组，以剖析性别偏向的基因表达。我们发现雌性和雄性之间免疫反应的时间动态和调节存在显著差异。我们的结果阐明了参与未折叠蛋白反应（UPR）、脂质代谢和炎症反应的性别分化途径，包括雌性偏向的IRE1/XBP1激活以及雄性偏向的代谢重编程与IL-1和AP-1途径之间的相互作用。总体而言，我们的研究为免疫反应转录调控中的性别差异提供了分子见解，并有助于更好地理解流感发病机制中的性别偏向。
