Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Graduate Program in Microbiology & Immunology, Vanderbilt University, Nashville, Tennessee, USA.
Infect Immun. 2019 Apr 23;87(5). doi: 10.1128/IAI.00031-19. Print 2019 Mar.
Coagulation and inflammation are interconnected, suggesting that coagulation plays a key role in the inflammatory response to pathogens. A phenome-wide association study (PheWAS) was used to identify clinical phenotypes of patients with a polymorphism in coagulation factor X. Patients with this single nucleotide polymorphism (SNP) were more likely to be hospitalized with hemostatic and infection-related disorders, suggesting that factor X contributes to the immune response to infection. To investigate this, we modeled infections by human pathogens in a mouse model of factor X deficiency. Factor X-deficient mice were protected from systemic infection, suggesting that factor X plays a role in the immune response to Factor X deficiency was associated with reduced cytokine and chemokine production and alterations in immune cell population during infection: factor X-deficient mice demonstrated increased abundance of neutrophils, macrophages, and effector T cells. Together, these results suggest that factor X activity is associated with an inefficient immune response and contributes to the pathology of infection.
凝血和炎症相互关联，这表明凝血在病原体引起的炎症反应中起着关键作用。一项表型全基因组关联研究（PheWAS）用于鉴定凝血因子 X 基因突变患者的临床表型。具有这种单核苷酸多态性（SNP）的患者更有可能因止血和感染相关疾病住院，这表明因子 X 有助于对感染的免疫反应。为了研究这一点，我们在因子 X 缺乏的小鼠模型中模拟了人类病原体感染。因子 X 缺乏的小鼠对系统性感染有保护作用，这表明因子 X 在免疫反应中发挥作用。因子 X 缺乏与感染期间细胞因子和趋化因子产生减少以及免疫细胞群体改变有关：因子 X 缺乏的小鼠中性粒细胞、巨噬细胞和效应 T 细胞的丰度增加。总之，这些结果表明因子 X 的活性与低效的免疫反应有关，并导致感染的病理变化。
