Department of Molecular Microbiology & Immunology, School of Medicine, University of Missouri, Columbia, MO 65212, USA.
Division of Biological Sciences, College of Arts & Science, University of Missouri, Columbia, MO 65212, USA.
Cell Rep. 2023 Aug 29;42(8):113007. doi: 10.1016/j.celrep.2023.113007. Epub 2023 Aug 16.
Immune responses differ between females and males, although such sex-based variance is incompletely understood. Observing that bacteremia of the opportunistic pathogen Burkholderia gladioli caused many more deaths of female than male mice bearing genetic deficiencies in adaptive immunity, we determined that this was associated with sex bias in the innate immune memory response called trained immunity. Female attenuation of trained immunity varies with estrous cycle stage and correlates with serum progesterone, a hormone that decreases glycolytic capacity and recall cytokine secretion induced by antigen non-specific stimuli. Progesterone receptor antagonism rescues female trained immune responses and survival from controlled B. gladioli infection to magnitudes similar to those of males. These data demonstrate progesterone-dependent sex bias in trained immunity where attenuation of female responses is associated with survival outcomes from opportunistic infection.
免疫反应在女性和男性之间存在差异，尽管这种基于性别的差异尚未完全被理解。我们观察到机会性病原体伯克霍尔德菌（Burkholderia gladioli）引起的菌血症导致具有适应性免疫遗传缺陷的雌性小鼠比雄性小鼠死亡更多，这表明这与称为训练免疫的固有免疫记忆反应中的性别偏见有关。女性训练免疫的衰减随发情周期阶段而变化，并与血清孕激素相关，孕激素是一种降低糖酵解能力并减少非特异性抗原刺激诱导的细胞因子分泌的激素。孕激素受体拮抗剂可挽救女性的训练免疫反应和生存能力，使其免受控制的伯克霍尔德菌感染，其程度与男性相似。这些数据表明，训练免疫存在孕激素依赖性性别偏见，女性反应的衰减与机会性感染的生存结果相关。
