Riaz Syeda Mariam, Hanevik Kurt, Sviland Lisbet, Mustafa Tehmina
Centre for International Health, Department of Global Public Health and Primary Care, Faculty of Medicine and Dentistry, University of Bergen, 5020 Bergen, Norway.
Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, 5020 Bergen, Norway.
Pathogens. 2025 Feb 25;14(3):224. doi: 10.3390/pathogens14030224.
Primary and post-primary TB are distinct entities. Primary TB occurs when the patient is infected with Mycobacterium tuberculosis (MTB) for the first time without prior immunity, and post-primary TB occurs when the patient has developed immunity against the primary infection. Post-primary TB occurs only in humans. It accounts for 80% of all clinical cases and nearly 100% of transmissions of infection. Early lesions of post-primary TB are reversible, and studying it using modern immunological tools holds the key to developing preventive or treatment strategies. Human lung tissue from untreated TB patients was acquired from pathology archives stored at the Gades Institute of Pathology, Haukeland University Hospital, Bergen, Norway, from 1931 to 1947. Manual immunohistochemistry was performed for macrophage (CD68, CD64 and CD163), T cells (CD3 and CD8), matrix metalloproteinases (MMP-9), and markers for programmed death-pathway PD/PDL-1. Digital quantification was performed using Qupath software. In early lesions of post-primary TB, macrophages showed mixed-phenotype M1 and M2, expressed PDL-1, and were compartmentalized in the alveolar space. T-cells expressed PD-1 and were compartmentalized in the interstitial wall surrounding early lesions. MTB antigens and MMP-9 were also found in early lesions. As the lesion progressed towards necrosis, macrophages showed predominant M1 morphology, and expressions of PDL-1, PD-1, CD8 cells, and MTB antigens increased. In the early lesions of post-primary TB, the compartmentalization of macrophages in the alveoli and T cells in the interstitium was shown. The PDL-PD1 pathway probably facilitated the mycobacterial growth by evading host immunity.
原发性肺结核和原发性后肺结核是不同的实体。原发性肺结核发生在患者首次感染结核分枝杆菌（MTB）且无先前免疫力时，而原发性后肺结核发生在患者已对原发性感染产生免疫力时。原发性后肺结核仅发生在人类中。它占所有临床病例的80%，几乎占所有感染传播的100%。原发性后肺结核的早期病变是可逆的，使用现代免疫学工具对其进行研究是制定预防或治疗策略的关键。来自未治疗肺结核患者的人肺组织取自挪威卑尔根豪克兰大学医院加德病理学研究所保存的1931年至1947年的病理档案。对巨噬细胞（CD68、CD64和CD163）、T细胞（CD3和CD8）、基质金属蛋白酶（MMP-9）以及程序性死亡途径PD/PDL-1的标志物进行手动免疫组织化学检测。使用Qupath软件进行数字定量分析。在原发性后肺结核的早期病变中，巨噬细胞表现出混合表型的M1和M2，表达PDL-1，并在肺泡空间中分隔分布。T细胞表达PD-1，并在早期病变周围的间质壁中分隔分布。在早期病变中也发现了MTB抗原和MMP-9。随着病变进展至坏死，巨噬细胞表现出主要的M1形态，并且PDL-1、PD-1、CD8细胞和MTB抗原的表达增加。在原发性后肺结核的早期病变中，显示出肺泡中的巨噬细胞和间质中的T细胞的分隔分布。PDL-PD1途径可能通过逃避宿主免疫来促进分枝杆菌生长。
