Electron Microscopy Centre Amsterdam, Amsterdam University Medical Centre AMC, Amsterdam, The Netherlands.
Netherlands Cancer Institute, Amsterdam, The Netherlands.
mSphere. 2021 May 5;6(3):e00153-21. doi: 10.1128/mSphere.00153-21.
infections claim more than a million lives each year, and better treatments or vaccines are required. A crucial pathogenicity factor is translocation from phagolysosomes to the cytosol upon phagocytosis by macrophages. Translocation from the phagolysosome to the cytosol is an ESX-1-dependent process, as previously shown Here, we show that , mycobacteria also translocate to the cytosol but mainly when host immunity is compromised. We observed only low numbers of cytosolic bacilli in mice, armadillos, zebrafish, and patient material infected with , , or In contrast, when innate or adaptive immunity was compromised, as in severe combined immunodeficiency (SCID) or interleukin-1 receptor 1 (IL-1R1)-deficient mice, significant numbers of cytosolic bacilli were detected in the lungs of infected mice. Taken together, , translocation to the cytosol of is controlled by adaptive immune responses as well as IL-1R1-mediated signals. For decades, has been one of the deadliest pathogens known. Despite infecting approximately one-third of the human population, no effective treatment or vaccine is available. A crucial pathogenicity factor is subcellular localization, as can translocate from phagolysosome to the cytosol in macrophages. The situation is more complicated. In this study, we establish that high-level cytosolic escape of mycobacteria can indeed occur but mainly when host resistance is compromised. The IL-1 pathway is crucial for the control of the number of cytosolic mycobacteria. The establishment that immune signals result in the clearance of cells containing cytosolic mycobacteria connects two important fields, cell biology and immunology, which is vital for the understanding of the pathology of .
每年有超过 100 万人死于感染，因此需要更好的治疗方法或疫苗。一个关键的致病性因素是在被巨噬细胞吞噬后从吞噬体到细胞质的易位。以前的研究表明，易位到细胞质是 ESX-1 依赖性的过程。在这里，我们表明，分枝杆菌也易位到细胞质，但主要是在宿主免疫力受损时。我们仅在感染了 、 或 的小鼠、犰狳、斑马鱼和患者材料中观察到低数量的细胞质杆菌。相比之下，当先天或适应性免疫受到损害时，如在严重联合免疫缺陷 (SCID) 或白细胞介素-1 受体 1 (IL-1R1) 缺陷型小鼠中，感染小鼠肺部会检测到大量细胞质杆菌。总之，分枝杆菌易位到细胞质受到适应性免疫反应以及 IL-1R1 介导的信号的控制。几十年来，一直是已知最致命的病原体之一。尽管大约三分之一的人口受到感染，但仍没有有效的治疗方法或疫苗。一个关键的致病性因素是亚细胞定位，因为可以从巨噬细胞的吞噬体易位到细胞质。的情况更为复杂。在这项研究中，我们确定分枝杆菌的高水平细胞质逃逸确实会发生，但主要是在宿主抵抗力受损时。IL-1 途径对于控制细胞质分枝杆菌的数量至关重要。免疫信号导致含有细胞质分枝杆菌的细胞被清除的发现将细胞生物学和免疫学这两个重要领域联系起来，这对于理解的病理学至关重要。
