Brighenti S, Joosten S A
Department of Medicine, Center for Infectious Medicine (CIM), Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden.
Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
J Intern Med. 2018 May 27. doi: 10.1111/joim.12778.
Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN-γ producing CD4 T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T-cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.
结核病（TB）中的保护性免疫是结核病研究界争论的主题，因为这对于全面理解结核病发病机制、开发用于结核病诊断和预后的新的有前景的工具以及更有效的结核病疫苗至关重要。产生干扰素-γ的CD4 T细胞在结核病控制中起关键作用，但可能不足以提供保护。已鉴定出有助于保护的其他亚群，如多功能和细胞溶解性T细胞亚群，包括经典和非经典T细胞以及由训练免疫产生的新型固有免疫细胞亚群。然而，要定义针对结核病的保护性免疫反应，还必须考虑平衡结核病免疫的复杂性。在这篇综述中，将讨论对效应细胞免疫以及调节细胞、相关合并症和宿主微生物群如何调节效应细胞免疫的见解。我们系统地描绘了不同的抑制性免疫细胞亚群如何在感染局部部位影响效应细胞反应。我们还剖析了常见合并症，如艾滋病毒、蠕虫感染和糖尿病，如何使保护性结核病免疫偏向致病性和调节性反应。最后，肺部和肠道微生物群的组成和多样性也可能影响宿主结核病免疫。了解人类宿主免疫平衡的这些不同方面对于预防结核病感染和疾病至关重要。
