Sex-specific effects of obestity on Influenza A virus infection and immunity

项目摘要 肥胖是传染病和疫苗接种后不良结局的重要并发症。在 在人类和小鼠模型中，肥胖与甲型流感病毒（IAV）感染的严重后果相关 和流感疫苗接种后的低保护性。在非肥胖的人类和小鼠模型中，我们已经表明， 生物学性别在IAV的发病机制和免疫应答中起重要作用， 性类固醇激素和性染色体。但是，目前我们不知道任何关于如何 生物学性别改变肥胖人群中IAV感染和免疫的结果。肥胖男性和 女性在肥胖、脂肪因子可用性、炎症细胞和细胞因子方面彼此不同 浓度的因此，我们假设肥胖改变了IAV感染的结果， 以针对性别的方式提供豁免和保护。使用肥胖小鼠模型，在aim1中，我们将研究性别 目的2将实验IAV疫苗诱导的性别特异性差异， 豁免和保护。脂肪因子、炎性细胞和细胞因子、B和T细胞反应的关联， 和性类固醇激素与IAV发病机制和免疫反应将探讨肥胖和 非肥胖雄性和雌性小鼠。因此，这项研究将填补我们理解中存在的关键空白， 生物学性别与肥胖在IAV感染和免疫中相互作用这将开辟新的途径， 优化流感疗法和疫苗，为肥胖人群提供更好的保护效果。

Project Summary Obesity is an important comorbidity for worse outcomes from infectious diseases and following vaccination. In humans and mouse models, obesity is associated with severe outcomes from influenza A virus (IAV) infection and inferior protection after influenza vaccination. In non-obese humans and mouse models, we have shown that biological sex plays significant role on IAV pathogenesis and immune responses, mediated by differences in sex steroid hormones and sex chromosomes. However, at present we do not know anything regarding how biological sex modifies the outcomes of IAV infection and immunity in obese population. Obese males and females differ with each other in terms of adiposity, adipokines availability, and inflammatory cells and cytokine concentrations. Therefore, we hypothesize that obesity alters the outcomes of IAV infection and vaccine-induced immunity and protection in a sex-specific manner. Using a mouse model of obesity, in aim 1, we will study sex differences during IAV pathogenesis while aim 2 will experiment sex-specific differences in IAV-vaccine induced immunity and protection. Associations of adipokines, inflammatory cells and cytokines, B and T-cell responses, and sex steroid hormones with IAV pathogenesis and immune responses will be explored among obese and non-obese male and female mice. Thus, this study will fill the critical gap existing in our understanding of interaction between biological sex and obesity during IAV infection and immunity. This will open new avenues to optimize influenza therapeutics and vaccines with better protective efficacies for the obese population.