St George and Sutherland Clinical School, Faculty of Medicine, University of New South Wales Australia, Research and Education Centre, Sydney, New South Wales, Australia.
Department of Infectious Disease, Immunology and Sexual Health, St George Hospital, Kogarah, New South Wales, Australia.
Sci Rep. 2017 Aug 15;7(1):8201. doi: 10.1038/s41598-017-07945-8.
The immune responses of males and females to bacterial infections display differences. The mechanisms that underlie this sexual dimorphism are multifactorial. Lipopolysaccharide (LPS) contributes to the pathogenesis of endotoxaemia. We have previously demonstrated that the plasma protein beta-2 glycoprotein-1 (β2GPI) reduces LPS-induced inflammation in male mice. In the present study using a more robust infection model of septicaemia the role of β2GPI is examined in both male and female wild type (WT) and β2GPI deficient (β2GPI) mice challenged with Escherichia coli (E. coli) intravenously. β2GPI deficiency led to an increase of E. coli colony forming units (CFU) in the circulation of both male and female mice. In male β2GPI mice this was associated with a worse clinical severity score. This difference was not observed between female β2GPI and female WT mice. Male WT mice had decreased levels of total and increased levels of free thiol β2GPI following administration of LPS or E. coli. This pattern of sexual dimorphic response was also observed in our cohort of humans with sepsis. These findings support a role for β2GPI in modulating the sex-specific susceptibility to gram-negative septicaemia.
男性和女性对细菌感染的免疫反应存在差异。这种性别二态性的机制是多因素的。脂多糖（LPS）有助于内毒素血症的发病机制。我们之前已经证明，血浆蛋白β-2 糖蛋白-1（β2GPI）可降低雄性小鼠中 LPS 诱导的炎症。在本研究中，我们使用了一种更为强大的败血症感染模型，研究了β2GPI 在雄性和雌性野生型（WT）和β2GPI 缺陷型（β2GPI）小鼠中对大肠杆菌（E. coli）静脉内感染的作用。β2GPI 缺陷导致雌雄小鼠的循环中大肠杆菌菌落形成单位（CFU）增加。在雄性β2GPI 小鼠中，这与更严重的临床严重程度评分有关。在雌性β2GPI 和雌性 WT 小鼠之间没有观察到这种差异。雄性 WT 小鼠在给予 LPS 或 E. coli 后，总β2GPI 水平降低，游离巯基β2GPI 水平升高。这种性别二态性反应模式也在我们的败血症患者队列中观察到。这些发现支持β2GPI 在调节革兰氏阴性菌败血症的性别特异性易感性方面的作用。
