Chemistry Core

结核分枝杆菌（Mycobacterium tuberculosis，Mtb）是世界上最成功的病原体之一。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 结核分枝杆菌抗原这些个体被认为具有实际或潜在的潜伏性Mtb感染（LTBl）。 其中，不能前瞻性识别的少数人将发展为再活化结核病（TB） 尽管他们的免疫力很正常活动性结核病可以传染给那些以前 未暴露的和具有LTB 1的那些，并且如果不治疗通常是致命的。足够数量的CD 4 T细胞，肿瘤 坏死因子α（TNFα）和干扰素γ（IFNγ）是控制原发性肝癌的有效决定因素。 结核病，但绝大多数艾滋病毒阴性的结核病复发患者在这些方面没有明确的缺陷， 途径。Mtb在人类宿主中保持潜伏的能力，以及人类宿主的相关失败， 免疫系统杀灭潜伏感染个体中Mtb的能力知之甚少。抗菌治疗 对药物敏感的结核分枝杆菌的活动性感染是有效的，但目前的药物必须给予6个月才能达到 无复发治愈率> 95%。这种延长治疗时间的必要性是由于 基因药物敏感性Mtb采取表型药物耐受性的持续状态的能力， 很容易被现有的药物消毒。尽管为了解结核病的这两个关键特征做出了大量努力， 感染潜伏期和持续性-基本问题仍然是关于遗传，免疫学， 微生物对两者都有贡献。我们力求通过结核病研究股缩小这一知识差距 （TBRU）联合威尔康奈尔医学院（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，并借鉴患者 在世界医学中心附属的海地GHESKIO中心， 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.