Cadena Anthony M, Fortune Sarah M, Flynn JoAnne L
Department of Microbiology and Molecular Genetics, 450 Technology Drive, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, USA.
Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts 02115, USA.
Nat Rev Immunol. 2017 Nov;17(11):691-702. doi: 10.1038/nri.2017.69. Epub 2017 Jul 24.
Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), results in a range of clinical presentations in humans. Most infections manifest as a clinically asymptomatic, contained state that is termed latent TB infection (LTBI); a smaller subset of infected individuals present with symptomatic, active TB. Within these two seemingly binary states, there is a spectrum of host outcomes that have varying symptoms, microbiologies, immune responses and pathologies. Recently, it has become apparent that there is diversity of infection even within a single individual. A good understanding of the heterogeneity that is intrinsic to TB - at both the population level and the individual level - is crucial to inform the development of intervention strategies that account for and target the unique, complex and independent nature of the local host-pathogen interactions that occur in this infection. In this Review, we draw on model systems and human data to discuss multiple facets of TB biology and their relationship to the overall heterogeneity observed in the human disease.
结核分枝杆菌是结核病(TB)的病原体,其感染会导致人类出现一系列临床表现。大多数感染表现为临床上无症状的潜伏状态,即潜伏性结核感染(LTBI);一小部分受感染个体表现为有症状的活动性结核病。在这两种看似二元的状态中,存在一系列具有不同症状、微生物学、免疫反应和病理学的宿主结局。最近,很明显即使在单个个体内也存在感染多样性。充分了解结核病在人群水平和个体水平上固有的异质性,对于制定干预策略至关重要,这些策略要考虑并针对这种感染中发生的局部宿主-病原体相互作用的独特、复杂和独立性质。在本综述中,我们利用模型系统和人类数据来讨论结核病生物学的多个方面及其与人类疾病中观察到的整体异质性的关系。