'"Why me, why now?" Using clinical immunology and epidemiology to explain who gets nontuberculous mycobacterial infection.

M Alexandra Lake,David M Lowe,Lyn R Ambrose,Marc C I Lipman

doi:10.1186/s12916-016-0606-6

Abstract

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.

Highlights

The prevalence of nontuberculous mycobacterial (NTM) disease is rising
Summary: 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
It was not until the human immunodeficiency virus (HIV) pandemic highlighted disseminated Mycobacterium avium and intracellulare as major opportunistic infection syndromes that their significance was recognised by the general healthcare community, a role further cemented by the expansion of iatrogenic immunosuppression

Summary

Discussion

Lessons from primary immune deficiencies CLINICAL VIGNETTE: A 2-year old boy born to firstcousin parents presents with several weeks of fever, weight loss, diarrhoea and skin nodules. B cell targeted therapies cases of NTM infection have been associated with the anti-CD20 monoclonal rituximab, reports remain rare and are usually in patients receiving other immunosuppressives [116], while the risk of TB is not significantly increased [114]. This is consistent with a relatively minor role for B cells and antibodies in host defence against mycobacteria. Author details 1Royal Free London NHS Foundation Trust, London, UK. 2Division of Infection and Immunity, University College London, London, UK. 3Institute of Immunity and Transplantation, University College London, Royal Free Campus, Pond Street, London NW3 2QG, UK. 4UCL Respiratory, Division of Medicine, Faculty of Medical Sciences, University College London, Royal Free Campus, London, UK

Findings

Background