Pharmacology

结核分枝杆菌(Mtb)是世界上最成功的病原体之一。据世卫组织估计， 世界上三分之一的人口的皮肤测试呈阳性，反映了长期的适应性免疫反应 对结核分枝杆菌抗原。这些人被认为有实际或潜在的结核分枝杆菌潜伏感染(LTB 1)。 其中，少数人不能被预期识别，将发展为再激活结核病(TB)。 尽管有明显的正常免疫力。活动性结核病可能对以前患有结核病的人具有传染性 未暴露的和患有LTBl的人，如果不治疗，通常是致命的。足够数量的CD4T细胞，肿瘤 肿瘤坏死因子α和干扰素γ是已证实的控制原发疾病的决定因素 结核病，但绝大多数HIV阴性的复活结核病患者在这些方面没有明确的缺陷 小路。结核分枝杆菌在人类宿主内保持潜伏的能力，以及人类的相关失败 免疫系统对潜伏感染的结核分枝杆菌的灭菌作用还知之甚少。抗菌治疗 对药物敏感的结核分枝杆菌活动性感染是有效的，但目前的药物必须服用6个月才能达到 无复发治愈率达95%。之所以需要这样长时间的治疗，是因为 遗传药物敏感型结核分枝杆菌采取表型耐药、持久状态的能力，而不是 容易被现有药物消毒的。尽管为理解结核分枝杆菌的这两个关键特征付出了大量努力 感染-潜伏期和持久性-基本问题仍然存在，涉及遗传、免疫学和 微生物对两者都有贡献。我们寻求通过一个结核病研究单位缩小这一知识差距 (TBRU)，联合了威尔·康奈尔医学院(WCMC)、洛克菲勒大学(RU)和 纪念斯隆·凯特琳癌症中心(MSKCC)，与选定的外部合作者，并吸引患者 在海地WCMC附属的GHESKIO中心提供对MTB的潜伏期和持久性的见解 人类感染。

Mycobacterium tuberculosis (Mtb) is one of the world's most successful pathogens. WHO estimates that about one third of the world's population has a positive skin test that reflects a long-term adaptive immune response to Mtb antigens. These individuals are considered to have actual or potential latent Mtb infection (LTBl). Among them, a minority that cannot be identified prospectively will develop reactivation tuberculosis (TB) despite having apparently normal immunity. Active TB can be contagious both to those who were previously unexposed and those with LTBl and is usually lethal if untreated. Adequate numbers of CD4 T cells, tumor necrosis factor alpha (TNFα), and interferon-gamma (IFNγ) are validated determinants of control of primary TB, but the vast majority of HIV negative patients with reactivation TB do not have defined defects in these pathways. The ability of Mtb to remain latent within the human host, and the related failure of the human immune system to sterilize Mtb in latently infected individuals, are poorly understood. Antimicrobial therapy for active infection by drug-sensitive Mtb is effective, but current drugs must be given for 6 months to achieve relapse-free cure rates of >95%. The necessity for this prolonged duration of therapy is attributable to the ability of genetically drug-sensitive Mtb to adopt a phenotypically drug-tolerant, persistent state in which it is not readily sterilized by current drugs. Despite substantial efforts to understand these two critical features of Mtb infection—latency and persistence—fundamental questions remain about the genetic, immunologic, and microbiologic contributors to both. We seek to close this knowledge gap through a Tuberculosis Research Unit (TBRU) that unites investigators at Weill Cornell Medical College (WCMC), Rockefeller University (RU), and Memorial Sloan Kettering Cancer Center (MSKCC), with selected external collaborators, and draws on patients at the WCMC-affiliated GHESKIO Centres in Haiti to provide insight into latency and persistence of Mtb during human infection.