Lake M Alexandra, Ambrose Lyn R, Lipman Marc C I, Lowe David M
Royal Free London NHS Foundation Trust, London, UK.
Division of Infection and Immunity, University College London, London, UK.
BMC Med. 2016 Mar 23;14:54. doi: 10.1186/s12916-016-0606-6.
The prevalence of nontuberculous mycobacterial (NTM) disease is rising. An understanding of known risk factors for disease sheds light on the immunological and physical barriers to infection, and how and why they may be overcome. This review focuses on human NTM infection, supported by experimental and in vitro data of relevance to the practising clinician who seeks to understand why their patient has NTM infection and how to further investigate.
First, the underlying immune response to NTM disease is examined. Important insights regarding NTM disease susceptibility come from nature's own knockouts, the primary immune deficiency disorders. We summarise the current knowledge surrounding interferon-gamma (IFNγ)-interleukin-12 (IL-12) axis abnormalities, followed by a review of phagocytic defects, T cell lymphopenia and rarer genetic conditions known to predispose to NTM disease. We discuss how these define key immune pathways involved in the host response to NTM. Iatrogenic immunosuppression is also important, and we evaluate the impact of novel biological therapies, as well as bone marrow transplant and chemotherapy for solid organ malignancy, on the epidemiology and presentation of NTM disease, and discuss the host defence dynamics thus revealed. NTM infection and disease in the context of other chronic illnesses including HIV and malnutrition is reviewed. The role of physical barriers to infection is explored. We describe how their compromise through different mechanisms including cystic fibrosis, bronchiectasis and smoking-related lung disease can result in pulmonary NTM colonisation or infection. We also summarise further associations with host factors including body habitus and age. We use the presented data to develop an over-arching model that describes human host defences against NTM infection, where they may fail, and how this framework can be applied to investigation in routine clinical practice.
非结核分枝杆菌（NTM）疾病的患病率正在上升。了解已知的疾病危险因素有助于揭示感染的免疫和物理屏障，以及它们如何被克服以及为何被克服。本综述聚焦于人类NTM感染，得到了与临床医生相关的实验和体外数据的支持，这些临床医生试图了解患者为何感染NTM以及如何进一步进行调查。
首先，研究了对NTM疾病的潜在免疫反应。关于NTM疾病易感性的重要见解来自于自然的基因敲除，即原发性免疫缺陷疾病。我们总结了围绕干扰素-γ（IFNγ）-白细胞介素-12（IL-12）轴异常的现有知识，随后回顾了吞噬缺陷、T细胞淋巴细胞减少以及已知易患NTM疾病的罕见遗传状况。我们讨论了这些如何定义宿主对NTM反应中涉及的关键免疫途径。医源性免疫抑制也很重要，我们评估了新型生物疗法以及实体器官恶性肿瘤的骨髓移植和化疗对NTM疾病的流行病学和临床表现的影响，并讨论由此揭示的宿主防御动态。还综述了包括HIV和营养不良在内的其他慢性疾病背景下的NTM感染和疾病。探讨了感染的物理屏障的作用。我们描述了它们通过不同机制（包括囊性纤维化、支气管扩张和吸烟相关的肺部疾病）受到损害如何导致肺部NTM定植或感染。我们还总结了与宿主因素（包括体型和年龄）的进一步关联。我们利用所呈现的数据建立了一个总体模型，该模型描述了人类宿主对NTM感染的防御、它们可能失败的地方以及如何将这个框架应用于常规临床实践中的调查。
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