Division of Molecular Biology and Human Genetics, Department of Science and Innovation-National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Faculty of Medicine and Health Sciences, South African Medical Research Council Centre for Tuberculosis Research, Stellenbosch University, Cape Town, South Africa.
Front Immunol. 2021 Mar 4;12:639605. doi: 10.3389/fimmu.2021.639605. eCollection 2021.
has the largest host range of the complex and infects domestic animal species, wildlife, and humans. The presence of global wildlife maintenance hosts complicates bovine tuberculosis (bTB) control efforts and further threatens livestock and wildlife-related industries. Thus, it is imperative that early and accurate detection of in all affected animal species is achieved. Further, an improved understanding of the complex species-specific host immune responses to could enable the development of diagnostic tests that not only identify infected animals but distinguish between infection and active disease. The primary bTB screening standard worldwide remains the tuberculin skin test (TST) that presents several test performance and logistical limitations. Hence additional tests are used, most commonly an interferon-gamma (IFN-γ) release assay (IGRA) that, similar to the TST, measures a cell-mediated immune (CMI) response to . There are various cytokines and chemokines, in addition to IFN-γ, involved in the CMI component of host adaptive immunity. Due to the dominance of CMI-based responses to mycobacterial infection, cytokine and chemokine biomarkers have become a focus for diagnostic tests in livestock and wildlife. Therefore, this review describes the current understanding of host immune responses to as it pertains to the development of diagnostic tools using CMI-based biomarkers in both gene expression and protein release assays, and their limitations. Although the study of CMI biomarkers has advanced fundamental understanding of the complex host- interplay and bTB progression, resulting in development of several promising diagnostic assays, most of this research remains limited to cattle. Considering differences in host susceptibility, transmission and immune responses, and the wide variety of affected animal species, knowledge gaps continue to pose some of the biggest challenges to the improvement of and bTB diagnosis.
该复合体拥有最大的宿主范围，可感染家畜、野生动物和人类。全球野生动物维持宿主的存在使牛结核病（bTB）控制工作复杂化，并进一步威胁到与牲畜和野生动物相关的产业。因此，必须在所有受影响的动物物种中实现对 的早期和准确检测。此外，更好地了解该复合体对 的特定宿主免疫反应，能够开发出不仅可以识别感染动物，而且可以区分感染和活动性疾病的诊断测试。全球范围内，主要的 bTB 筛查标准仍然是结核菌素皮肤试验（TST），该试验存在一些测试性能和后勤限制。因此，会使用其他测试，最常用的是干扰素-γ（IFN-γ）释放试验（IGRA），该试验与 TST 类似，测量针对 的细胞介导免疫（CMI）反应。除 IFN-γ 外，还有多种细胞因子和趋化因子参与宿主适应性免疫的 CMI 成分。由于基于 CMI 的对分枝杆菌感染的反应占主导地位，因此细胞因子和趋化因子生物标志物已成为在牲畜和野生动物中用于诊断测试的重点。因此，本综述描述了宿主对 的免疫反应的当前理解，以及使用基于 CMI 的生物标志物在基因表达和蛋白释放测定中开发诊断工具的情况，同时还描述了这些工具的局限性。尽管 CMI 生物标志物的研究已经深入了解了复杂的宿主相互作用和 bTB 进展，从而开发了几种有前途的诊断检测方法，但这项研究大多仍然局限于牛。考虑到宿主易感性、传播和免疫反应的差异，以及受影响动物物种的多样性，知识差距仍然是改善 和 bTB 诊断的最大挑战之一。
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