RESTRAINT STRESS: MODULATION OF MYCOBACTERIAL RESISTANCE

描述（改编自申请人摘要）：人感染 免疫缺陷病毒导致系统性免疫抑制， 宿主对感染的易感性增加。 感染 机会致病菌是导致 与艾滋病有关。 分枝杆菌疾病的发病率，包括 由结核分枝杆菌和鸟引起的感染， 在艾滋病毒感染者中， 的研究 研究者实验室在MHC II类中存在相关差异 在小鼠中表达具有对分枝杆菌生长的抗性。 类似 人类单核细胞MHC II类分子表达的差异， 也被调查人员发现。 压力可能是 在对分枝杆菌疾病易感性的辅助因子，这个实验室 已经表明约束应力导致Ia的抑制 表情 Ia表达的差异表明， 小鼠中巨噬细胞活化水平的差异， 对分枝杆菌的生长有抵抗力或敏感性。 的目的 这一更新申请将确定压力在以下方面的作用： 调节分枝杆菌感染的发病机制， 这些差异与Ia表达的变化有关。 因此，约束应力 可以通过允许机会主义者 病原体在单核吞噬细胞内建立和生长。 具体目的是：（1）确定约束对 分枝杆菌在体内的生长情况;（2）确定是否限制应激 诱导的分枝杆菌生长的改变是由 下丘脑-垂体-肾上腺轴;（3）确定的作用， 交感神经系统在束缚应激介导的改变中的作用 分枝杆菌生长;（4）确定束缚应激对 巨噬细胞的体外活性;（5）确定其作用机制 束缚应激介导的巨噬细胞功能改变。

DESCRIPTION (Adapted form Applicant's Abstract):Infection with the human immunodeficiency virus leads to a systemic immunosuppression that results in an increase in the susceptibility of the host to infection. Infection by opportunistic pathogens is responsible for the morbidity and mortality associated with AIDS. The incidence of mycobacterial diseases, including infections caused by M tuberculosis and avium, has increased significantly among HIV-infected individuals. Studies in the investigator's laboratory have correlated differences in MHC class II expression with resistance to mycobacterial growth in mice. Similar differences in MHC class II expression by human monocytes have been identified also by the investigators. Stress may be an important cofactor in susceptibility to mycobacterial disease, and this laboratory has shown that restraint stress results in a suppression of Ia expression. Differences in Ia expression indicate that there may be differences in the level of activation of the macrophages in mice that are resistant or susceptible to mycobacterial growth. The purpose of this renewal application will be to determine the role of stress in modulating the pathogenesis of mycobacterial infection and to correlate these differences to changes in Ia expression. Thus, restraint stress may alter the host parasite relationship by allowing the opportunistic pathogen to become established and grown within mononuclear phagocytes. The specific aims are: (1) to determine the effect of restraint on the growth of Mycobacteria in vivo; (2) to determine whether restraint stress induced alteration in mycobacterial growth is mediated by the hypothalamic-pituitary-adrenal axis; (3) to determine the role of the sympathetic nervous system in restraint stress mediated alteration in mycobacterial growth; (4) to determine the effect of restraint stress on the in vitro activity of macrophages; and (5) to determine the mechanism of restraint stress mediated alteration in macrophage function.