Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston, Texas, USA.
Department of Pathology and Laboratory Medicine, McGovern Medical School, University of Texas Health Sciences Center-Houston, Houston, Texas, USA.
J Leukoc Biol. 2019 Aug;106(2):275-282. doi: 10.1002/JLB.MR0318-095RR. Epub 2019 Apr 2.
Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status. In contrast, in a small fraction of infected individuals, the host immune response fails to control the growth of M. tuberculosis bacilli, and granulomatous TB develops progressively. Elucidating the molecular and phenotypic events that govern the outcome of the infection within macrophages is fundamental to understanding the key features of these cells that could be equally critical in infection control. The molecular details of the M. tuberculosis-macrophage interaction continue to be discerned, and emerging evidence suggests that macrophage population that participate in infection is heterogeneous. While the local environment and developmental origin could influence the phenotypic heterogeneity and functional plasticity of macrophages, M. tuberculosis has also been demonstrated to modulate the polarization of macrophages. In this review, we draw on work investigating specialized macrophage populations and their interactions with M. tuberculosis with respect to pathogenesis and specific immune responses. Understanding the mechanisms that control the repertoire of macrophage phenotypes and behaviors during infection may provide prospects for novel TB control strategies through modulation of immunobiological functions of macrophages.
巨噬细胞是结核分枝杆菌（导致结核病（TB）的病原体）在人体细胞内生存的主要宿主细胞。该病原体具有在巨噬细胞的恶劣环境中生存的非凡能力。然而，初次感染并不会导致大多数人患上活动性结核病。大多数人仍然潜伏感染，细菌被宿主免疫反应所控制。然而，这些人在免疫状态下降后可能会发展为活动性结核病。相比之下，在一小部分感染个体中，宿主免疫反应无法控制结核分枝杆菌的生长，逐渐发展为肉芽肿性结核病。阐明控制感染在巨噬细胞内结果的分子和表型事件，对于理解这些细胞的关键特征至关重要，这些特征在感染控制中可能同样至关重要。结核分枝杆菌与巨噬细胞相互作用的分子细节仍在不断被揭示，新的证据表明，参与感染的巨噬细胞群体具有异质性。虽然局部环境和发育起源可以影响巨噬细胞的表型异质性和功能可塑性，但结核分枝杆菌也被证明可以调节巨噬细胞的极化。在这篇综述中，我们借鉴了研究专门的巨噬细胞群体及其与结核分枝杆菌相互作用的工作，以了解发病机制和特定的免疫反应。了解控制感染期间巨噬细胞表型和行为的机制可能为通过调节巨噬细胞的免疫生物学功能提供新的结核病控制策略的前景。
