结核病(TB)仍然是艾滋病毒感染者死亡的主要原因,以进行性肺部炎症为特征。尽管结核病的标志是局灶性肉芽肿性肺病变,我们对HIV和TB合并感染的组织病理学特征和炎症调节的理解仍然不完整.在这项研究中,我们旨在通过对HIV和TB合并感染和TB患者的免疫组织化学分析来阐明这些组织病理学特征,揭示了明显的差异。值得注意的是,HIV和TB肉芽肿表现出CD68+巨噬细胞(Mφ)的聚集,而结核病病变主要表现为CD20+B细胞聚集,突出共同感染中不同的免疫反应。空间转录组分析进一步阐明了CD68+Mφ在HIV和TB中的聚集,伴随着IL6途径的激活,可能加剧炎症。通过多重免疫染色,我们在HIV和TB中验证了两种肉芽肿类型,在TB中验证了三种,以细胞架构为特征。值得注意的是,在两种类型的HIV和TB肉芽肿中,CD68+Mφ高表达IL6R/pSTAT3,对比TB肉芽肿高表达IFNGRA/SOCS3,表明不同的信号通路在起作用。因此,IL6途径的激活可能会加剧HIV和TB肺部的炎症,而富含SOCS3的免疫微环境抑制IL6诱导的结核病过度炎症。这些发现为HIV和TB肉芽肿的形成提供了重要的见解,照亮潜在的治疗靶点,特别是对于HIV和TB共同感染下的肉芽肿性肺部。我们的研究强调了全面了解HIV和TB共感染的免疫发病机制的重要性,并提出了用SOCS3激活剂或抗IL6R剂靶向IL6信号以减轻HIV和TB共感染个体肺部炎症的潜在途径。
Tuberculosis (TB) remains a leading cause of mortality among individuals coinfected with HIV, characterized by progressive pulmonary inflammation. Despite TB\'s hallmark being focal granulomatous lung lesions, our understanding of the histopathological features and regulation of inflammation in HIV & TB coinfection remains incomplete. In this study, we aimed to elucidate these histopathological features through an immunohistochemistry analysis of HIV & TB co-infected and TB patients, revealing marked differences. Notably, HIV & TB granulomas exhibited aggregation of CD68 + macrophage (Mφ), while TB lesions predominantly featured aggregation of CD20+ B cells, highlighting distinct immune responses in coinfection. Spatial transcriptome profiling further elucidated CD68+ Mφ aggregation in HIV & TB, accompanied by activation of IL6 pathway, potentially exacerbating inflammation. Through multiplex immunostaining, we validated two granuloma types in HIV & TB versus three in TB, distinguished by cell architecture. Remarkably, in the two types of HIV & TB granulomas, CD68 + Mφ highly co-expressed IL6R/pSTAT3, contrasting TB granulomas\' high IFNGRA/SOCS3 expression, indicating different signaling pathways at play. Thus, activation of IL6 pathway may intensify inflammation in HIV & TB-lungs, while SOCS3-enriched immune microenvironment suppresses IL6-induced over-inflammation in TB. These findings provide crucial insights into HIV & TB granuloma formation, shedding light on potential therapeutic targets, particularly for granulomatous pulmonary under HIV & TB co-infection. Our study emphasizes the importance of a comprehensive understanding of the immunopathogenesis of HIV & TB coinfection and suggests potential avenues for targeting IL6 signaling with SOCS3 activators or anti-IL6R agents to mitigate lung inflammation in HIV & TB coinfected individuals.