幼年纯种小鼠感染流感后肺部持续炎症的性别差异

IF 3.6 2区 医学 Q1 PHYSIOLOGY American journal of physiology. Lung cellular and molecular physiology Pub Date : 2024-08-01 Epub Date: 2024-05-29 DOI:10.1152/ajplung.00407.2023
Brydie R Huckestein, Danielle Antos, Michelle L Manni, Kelly Zeng, Leigh M Miller, Kristen L Parenteau, Stacy L Gelhaus, Steven J Mullett, Jason E Shoemaker, John F Alcorn
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引用次数: 0

摘要

儿童是流感感染的易感人群,由于缺乏免疫力或原有免疫力有限,可能会出现严重的疾病表现。尽管流感对这一人群的影响不成比例,但对儿科流感的研究却缺乏关注,尤其是在确定病毒清除后长期结果的发病机制方面。在这项研究中,雌雄近交系幼鼠均感染了流感,并在病毒清除后进行了分析,以确定性别对流感持续炎症反应的影响。研究发现,流感病毒清除后,雌性小鼠的肺部细胞因子反应范围更广,几乎所有小鼠都有先天性、I型和II型细胞因子特征。另一方面,雄性小鼠的 IL-6 和其他巨噬细胞相关细胞因子水平较高,但没有 I 型或 II 型反应的证据。感染后雄性和雌性小鼠肺部的免疫状况相似,但雄性小鼠的调节性T细胞与TH1细胞的比例高于雌性小鼠。细胞因子的产生与TH1细胞和渗出巨噬细胞的频率以及支气管肺泡灌洗液中的细胞数量呈正相关。此外,雌性肺富含参与糖酵解途径的代谢物,这表明病毒清除后雌性肺中的糖酵解高于雄性。这些数据表明,幼年雌性小鼠在病毒清除后会出现持续和过度的肺部炎症,而幼年雄性小鼠则具有更强的免疫抑制表型。
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Sex-based differences in persistent lung inflammation following influenza infection of juvenile outbred mice.

Children are susceptible to influenza infections and can experience severe disease presentation due to a lack of or limited pre-existing immunity. Despite the disproportionate impact influenza has on this population, there is a lack of focus on pediatric influenza research, particularly when it comes to identifying the pathogenesis of long-term outcomes that persist beyond the point of viral clearance. In this study, juvenile outbred male and female mice were infected with influenza and analyzed following viral clearance to determine how sex impacts the persistent inflammatory responses to influenza. It was found that females maintained a broader cytokine response in the lung following clearance of influenza, with innate, type I and type II cytokine signatures in almost all mice. Males, on the other hand, had higher levels of IL-6 and other macrophage-related cytokines, but no evidence of a type I or type II response. The immune landscape was similar in the lungs between males and females postinfection, but males had a higher regulatory T cell to TH1 ratio compared with female mice. Cytokine production positively correlated with the frequency of TH1 cells and exudate macrophages, as well as the number of cells in the bronchoalveolar lavage fluid. Furthermore, female lungs were enriched for metabolites involved in the glycolytic pathway, suggesting glycolysis is higher in female lungs compared with males after viral clearance. These data suggest juvenile female mice have persistent and excessive lung inflammation beyond the point of viral clearance, whereas juvenile males had a more immunosuppressive phenotype.NEW & NOTEWORTHY This study identifies sex-based differences in persistent lung inflammation following influenza infection in an outbred, juvenile animal model of pediatric infection. These findings indicate the importance of considering sex and age as variable in infectious disease research.

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来源期刊
CiteScore
9.20
自引率
4.10%
发文量
146
审稿时长
2 months
期刊介绍: The American Journal of Physiology-Lung Cellular and Molecular Physiology publishes original research covering the broad scope of molecular, cellular, and integrative aspects of normal and abnormal function of cells and components of the respiratory system. Areas of interest include conducting airways, pulmonary circulation, lung endothelial and epithelial cells, the pleura, neuroendocrine and immunologic cells in the lung, neural cells involved in control of breathing, and cells of the diaphragm and thoracic muscles. The processes to be covered in the Journal include gas-exchange, metabolic control at the cellular level, intracellular signaling, gene expression, genomics, macromolecules and their turnover, cell-cell and cell-matrix interactions, cell motility, secretory mechanisms, membrane function, surfactant, matrix components, mucus and lining materials, lung defenses, macrophage function, transport of salt, water and protein, development and differentiation of the respiratory system, and response to the environment.
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