Effects and mechanisms of cold-induced stress on the development of chlamydia genital infection in a mouse model

寒冷应激对小鼠模型生殖器衣原体感染发生的影响及机制

• 批准号: 9099462
• 负责人: Tesfaye Belay
• 金额: $ 42.28万
• 依托单位: BLUEFIELD STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-12 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9099462
• 关键词: Adrenergic Agents; Affect; Agonist; Antigen-Presenting Cells; Atenolol; Bacterial Sexually Transmitted Diseases; Bone Marrow; CD4 Positive T Lymphocytes; Cell physiology; Cells; Cellular Stress; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Corticotropin-Releasing Hormone Receptors; Dendritic Cells; Development; Disease; Ectopic Pregnancy; Endocrine system; Epinephrine; Future; Gene Expression; Genetic screening method; Genital system; Health; Health Care Costs; Hormone Receptor; Hormones; Human; Immune; Immune response; Immune system; Immunity; In Vitro; Infection; Infertility; Interleukin-10; Interleukin-12; Intervention; Kinetics; Laboratories; Lead; Left; Marrow; Mature Bone; Measures; Mediating; Mus; Nadolol; Neurotransmitters; Norepinephrine; Norepinephrine Receptors; Pathogenesis; Pathology; Pelvic Inflammatory Disease; Predisposition; Process; Production; Receptor Cell; Regulation; Research Personnel; Resistance; Role; Severities; Sexually Transmitted Diseases; Signal Transduction; Spleen; Stress; Systems Analysis; T cell differentiation; T-Lymphocyte; Terbutaline; Testing; Th1/Th2 Differentiation Pathway; Time; United States; Water; Water Stress; Wild Type Mouse; Woman; astressin; beta-2 Adrenergic Receptors; beta-adrenergic receptor; bone; child bearing; cytokine; genital infection; human subject; immune function; immunopathology; interest; mouse model; public health relevance; receptor; reproductive tract; research study; stressor

 DESCRIPTION (provided by applicant): Genital infection by Chlamydia trachomatis is the most common bacterial sexually transmitted disease (STD) worldwide. If left untreated, chlamydia genital infection leads to complications such as pelvic inflammatory disease, ectopic pregnancy, and infertility. There is an increasing interest in understanding how stress may impact resistance or susceptibility to a number of diseases, including sexually transmitted disease. Many investigators have examined the immune response to C. trachomatis but the effect of stress has not yet been explored. We have demonstrated that prolonged exposure of mice to cold water results in increased intensity of chlamydia genital infection, but the mechanism(s) are not known. Chlamydial immunity is predominantly CD4+ T cell-mediated, and stressors that target T cell differentiation and activation by primary antigen- presenting cells such as dendritic cells are likely to affect immune response against chlamydia infection. The central objective of this proposal is to define the mechanism(s) by which stress may suppress the immune system and increase the intensity of genital C. trachomatis infection and immunopathologies in mice. Our hypothesis is that cold water-induced stress leads to norepinephrine (NE) modulation of immune response to disease sequelae by stimulation of beta-2 adrenergic receptor (β2AR) expression. At present we are against C. trachomatis genital infection by enhancing the production of immunopathogenic cytokines that lead examining in vitro the effect of synthetic NE on the proliferation of different mouse immune cells, including T cells, as measured by cytokine production. In Aim 1 of the proposed project, gene expression of beta adrenergic receptor subtypes on CD4+ T cells will be determined. In Aim 2 the kinetics of cytokines in maturing infection in β2AR-deficient and wild-type mice will be analyzed and compared. Results obtained from this of marrow-derived dendritic cells exposed to NE will be analyzed. In Aim 3, clearance of C. trachomatis genital stress study in mice will provide important new information on the interaction between the immune system and the endocrine system, which could lead to future development of countermeasures and interventions to control chlamydia genital infection and pathologies in human subjects.

 描述（由申请人提供）：沙眼衣原体生殖器感染是全球最常见的细菌性传播疾病（STD）。如果不及时治疗，衣原体生殖器感染会导致并发症，如盆腔炎，宫外孕和不孕症。人们越来越有兴趣了解压力如何影响对一些疾病的抵抗力或易感性，包括性传播疾病。许多研究者已经研究了对C.沙眼，但压力的影响尚未得到探讨。我们已经证明，小鼠长时间暴露在冷水中会导致生殖器衣原体感染强度增加，但其机制尚不清楚。衣原体免疫主要是CD4+ T细胞介导的，并且靶向T细胞分化和通过初级抗原呈递细胞如树突细胞活化的应激物可能影响针对衣原体感染的免疫应答。该提案的中心目标是确定应激可能抑制免疫系统并增加生殖器C强度的机制。沙眼感染和免疫病理学。我们的假设是，冷水诱导的应激导致去甲肾上腺素（NE）通过刺激β 2肾上腺素能受体（β2AR）表达来调节疾病后遗症的免疫反应。目前，我们反对C。通过增强免疫病原性细胞因子的产生来治疗沙眼生殖器感染，这导致体外检查合成NE对不同小鼠免疫细胞（包括T细胞）增殖的影响，如通过细胞因子产生所测量的。在拟议项目的目标1中，将确定CD4+ T细胞上β肾上腺素能受体亚型的基因表达。在目的2中，将分析和比较β 2AR缺陷型和野生型小鼠中成熟感染中细胞因子的动力学。将分析由此获得的暴露于NE的骨髓来源的树突状细胞的结果。目标3中，C.在小鼠中进行的沙眼衣原体生殖器应激研究将提供关于免疫系统和内分泌系统之间相互作用的重要新信息，这可能导致未来制定控制人类受试者生殖器衣原体感染和病理的对策和干预措施。