‘”Why me, why now?” Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection

BMC Medicine

Opinion

Lyn R. Ambrose¹  M. Alexandra Lake²  David M. Lowe³  Marc C. I. Lipman⁴ 

[1] Institute of Immunity and Transplantation, University College London, Royal Free Campus, Pond Street, NW3 2QG, London, UK;Royal Free London NHS Foundation Trust, London, UK;Division of Infection and Immunity, University College London, London, UK;Royal Free London NHS Foundation Trust, London, UK;Institute of Immunity and Transplantation, University College London, Royal Free Campus, Pond Street, NW3 2QG, London, UK;Royal Free London NHS Foundation Trust, London, UK;UCL Respiratory, Division of Medicine, Faculty of Medical Sciences, University College London, Royal Free Campus, London, UK;

关键词: Nontuberculous mycobacteria;    Host defence;    Primary immune deficiency;    Interferon gamma;    Interleukin 12;    Bronchiectasis;    Cystic fibrosis;    Immune response;   

DOI  :  10.1186/s12916-016-0606-6

 received in 2015-12-19, accepted in 2016-03-18,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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.DiscussionFirst, 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.SummaryWe 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.

【 授权许可】

CC BY   
© Lake et al. 2016