Laboratory of Pediatrics, Université Libre de Bruxelles, Brussels, Belgium.
Laboratory of Translational Research, Université Libre de Bruxelles, Brussels, Belgium.
Front Immunol. 2024 May 21;15:1379754. doi: 10.3389/fimmu.2024.1379754. eCollection 2024.
An increasing number of studies have highlighted the existence of a sex-specific immune response, wherein men experience a worse prognosis in cases of acute inflammatory diseases. Initially, this sex-dependent inflammatory response was attributed to the influence of sex hormones. However, a growing body of evidence has shifted the focus toward the influence of chromosomes rather than sex hormones in shaping these inflammatory sex disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated immune pathways have been implicated in driving the sex-specific immune response. These receptors are encoded by genes located on the X chromosome. TLRs are pivotal components of the innate immune system, playing crucial roles in responding to infectious diseases, including bacterial and viral pathogens, as well as trauma-related conditions. Importantly, the TLR-mediated inflammatory responses, as indicated by the production of specific proteins and cytokines, exhibit discernible sex-dependent patterns. In this review, we delve into the subject of sex bias in TLR activation and explore its clinical implications relatively to both the X chromosome and the hormonal environment. The overarching objective is to enhance our understanding of the fundamental mechanisms underlying these sex differences.
越来越多的研究强调了存在一种性别特异性免疫反应,即在急性炎症性疾病中,男性的预后更差。最初,这种性别依赖性炎症反应归因于性激素的影响。然而,越来越多的证据将焦点转移到染色体而不是性激素对形成这些炎症性别差异的影响上。值得注意的是,某些模式识别受体,如 Toll 样受体 (TLR) 及其相关的免疫途径,被认为在驱动性别特异性免疫反应中发挥作用。这些受体由位于 X 染色体上的基因编码。TLR 是先天免疫系统的关键组成部分,在应对传染病(包括细菌和病毒病原体以及与创伤相关的疾病)中发挥着至关重要的作用。重要的是,TLR 介导的炎症反应(如特定蛋白质和细胞因子的产生)表现出明显的性别依赖性模式。在这篇综述中,我们深入探讨了 TLR 激活中的性别偏见问题,并探讨了其与 X 染色体和激素环境相关的临床意义。总体目标是增强我们对这些性别差异背后基本机制的理解。