Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine.
Division of Medical Microbiology, Department of Pathology, University of Cape Town, Observatory, South Africa.
Curr Opin HIV AIDS. 2018 Nov;13(6):455-461. doi: 10.1097/COH.0000000000000501.
Tuberculosis is the leading infectious cause of death worldwide, and HIV-1 the best recognized risk factor for active TB. This review focuses on immune complex formation; the interplay of type I and II interferon signaling; and T-cell activation in HIV-TB pathogenesis.
Circulating immune complexes and complement, and Fcγ signaling in whole blood act as early markers of TB disease in HIV-1-infected persons. HIV-1 is associated with a type I interferon response in whole blood, reducing the specificity of TB biomarkers dependent on type I and II interferon genes. Type I and type II interferons are implicated in both protection and TB disease, a protective outcome may depend on modulating these pathways. Whilst M. tuberculosis-specific CD4 T cells are preferentially depleted during HIV-1 infection, activation markers on M. tuberculosis-specific CD4 T cells, in particular HLA-DR, reflect immune activation and have promise as biomarkers of M. tuberculosis disease activity in individuals with HIV-1.
TB pathogenesis in HIV-1 involves a complex interaction of underlying activation of both the innate and adaptive immune systems. Further research is required to understand whether biomarkers of activation could be used to predict or quantify TB disease in the context of HIV-1 infection.
结核病是全球主要的传染性致死病因，而 HIV-1 是活动性结核病的最佳公认危险因素。本综述重点关注免疫复合物形成、I 型和 II 型干扰素信号转导以及 T 细胞激活在 HIV-TB 发病机制中的作用。
循环免疫复合物和补体以及全血中的 Fcγ 信号在 HIV-1 感染者中作为结核病疾病的早期标志物。HIV-1 与全血中的 I 型干扰素反应相关，降低了依赖于 I 型和 II 型干扰素基因的 TB 生物标志物的特异性。I 型和 II 型干扰素均与保护和结核病疾病有关，保护结果可能取决于对这些途径的调节。虽然在 HIV-1 感染期间，结核分枝杆菌特异性 CD4 T 细胞优先耗竭，但结核分枝杆菌特异性 CD4 T 细胞上的激活标志物，特别是 HLA-DR，反映了免疫激活，并有望成为 HIV-1 感染者结核分枝杆菌疾病活动的生物标志物。
HIV-1 中的结核病发病机制涉及固有和适应性免疫系统的潜在激活的复杂相互作用。需要进一步研究以了解激活生物标志物是否可用于预测或量化 HIV-1 感染背景下的结核病疾病。
