Parashar Kaustubh, Kopping Erik, Frank David, Sampath Vinaya, Thanassi David G, Carpino Nick
Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, USA.
Center for Infectious Diseases, Stony Brook University, Stony Brook, New York, USA.
Infect Immun. 2017 Aug 18;85(9). doi: 10.1128/IAI.00406-17. Print 2017 Sep.
The uppressor of CR ignaling proteins (Sts-1 and Sts-2) are two homologous phosphatases that negatively regulate signaling pathways in a number of hematopoietic lineages, including T lymphocytes. Mice lacking Sts expression are characterized by enhanced T cell responses. Additionally, a recent study demonstrated that mice are profoundly resistant to systemic infection by , with resistance characterized by enhanced survival, more rapid fungal clearance in key peripheral organs, and an altered inflammatory response. To investigate the role of Sts in the primary host response to infection by a bacterial pathogen, we evaluated the response of mice to infection by a Gram-negative bacterial pathogen. is a facultative bacterial pathogen that replicates intracellularly within a variety of cell types and is the causative agent of tularemia. infections are characterized by a delayed immune response, followed by an intense inflammatory reaction that causes widespread tissue damage and septic shock. Herein, we demonstrate that mice lacking Sts expression are significantly resistant to infection by the ive accine train (LVS) of Resistance is characterized by reduced lethality following high-dose intradermal infection, an altered cytokine response in the spleen, and enhanced bacterial clearance in multiple peripheral organs. bone marrow-derived monocytes and neutrophils, infected with LVS , display enhanced restriction of intracellular bacteria. These observations suggest the Sts proteins play an important regulatory role in the host response to bacterial infection, and they underscore a role for Sts in regulating functionally relevant immune response pathways.
CR信号蛋白的抑制因子（Sts-1和Sts-2）是两种同源磷酸酶，它们对包括T淋巴细胞在内的多种造血谱系中的信号通路起负调控作用。缺乏Sts表达的小鼠的特征是T细胞反应增强。此外，最近一项研究表明，小鼠对……的全身感染具有高度抵抗力，其抵抗力表现为存活率提高、关键外周器官中真菌清除更快以及炎症反应改变。为了研究Sts在宿主对细菌病原体感染的初始反应中的作用，我们评估了……小鼠对革兰氏阴性细菌病原体感染的反应。……是一种兼性细菌病原体，可在多种细胞类型内进行细胞内复制，是兔热病的病原体。……感染的特征是免疫反应延迟，随后是强烈的炎症反应，导致广泛的组织损伤和感染性休克。在此，我们证明缺乏Sts表达的小鼠对……的活疫苗株（LVS）感染具有显著抵抗力。抵抗力表现为高剂量皮内感染后致死率降低、脾脏中细胞因子反应改变以及多个外周器官中细菌清除增强。用……LVS感染的骨髓来源的单核细胞和中性粒细胞对细胞内细菌的限制增强。这些观察结果表明，Sts蛋白在宿主对细菌感染的反应中起重要调节作用，并且它们强调了Sts在调节功能相关免疫反应途径中的作用。
