title: '"Why me, why now?" Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Royal Free London NHS Foundation Trust, London, UK.|Division of Infection and Immunity, University College London, London, UK.
authors.forename: M Alexandra
authors.initials: MA
authors.lastname: Lake
authors.affiliation: Institute of Immunity and Transplantation, University College London, Royal Free Campus, Pond Street, London, NW3 2QG, UK.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Ambrose
authors.affiliation: 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.
authors.forename: Marc C I
authors.initials: MC
authors.lastname: Lipman
authors.affiliation: Royal Free London NHS Foundation Trust, London, UK. d.lowe@ucl.ac.uk.|Institute of Immunity and Transplantation, University College London, Royal Free Campus, Pond Street, London, NW3 2QG, UK. d.lowe@ucl.ac.uk.
authors.forename: David M
authors.initials: DM
authors.lastname: Lowe
mesh_terms: D004198:Disease Susceptibility / Q000276:immunology*; D006801:Humans; D008297:Male; D009165:Mycobacterium Infections, Nontuberculous / Q000453:epidemiology* / Q000276:immunology*; D009170:Nontuberculous Mycobacteria / Q000276:immunology; D015995:Prevalence; D012307:Risk Factors
keywords: Bronchiectasis; Cystic fibrosis; Host defence; Immune response; Interferon gamma; Interleukin 12; Nontuberculous mycobacteria; Primary immune deficiency