A genetic perspective on granulomatous diseases with an emphasis on mycobacterial infections

• Published in: Seminars in immunopathology Vol. 38; no. 2; pp. 199 - 212
• Main Authors: Wu, Un-In, Holland, Steven M.
• Format: Journal Article Book Review
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2016; Springer Nature B.V
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Genetic Association Studies; Genetic Diseases, Inborn - complications; Genetic Diseases, Inborn - genetics; Genetic Diseases, Inborn - metabolism; Genetic Predisposition to Disease; Granuloma - etiology; Granuloma - metabolism; Granuloma - pathology; Host-Pathogen Interactions - genetics; Host-Pathogen Interactions - immunology; Humans; Immune System - immunology; Immune System - metabolism; Immune System - microbiology; Immune System - pathology; Immunology; Interferon-gamma - deficiency; Interferon-gamma - genetics; Interferon-gamma - metabolism; Interleukin-12 - deficiency; Interleukin-12 - genetics; Interleukin-12 - metabolism; Internal Medicine; Mycobacterium; Mycobacterium - immunology; Mycobacterium Infections - complications; Mycobacterium Infections - genetics; Mycobacterium Infections - immunology; Mycobacterium Infections - microbiology; Review; Risk Factors; Sequence Deletion; Signal Transduction; Nontuberculous; IFN-γ; Tuberculosis; IL-12; Mycobacteria
• ISSN: 1863-2297; 1863-2300; 1863-2300
• DOI: 10.1007/s00281-015-0552-y

Identification of the genetic factors predisposing to mycobacterial infections has been a subject of intense research activities. Current knowledge of the genetic and immunological basis of susceptibility to mycobacteria largely comes from natural human and experimental models of Bacille Calmette Guérin (BCG) and nontuberculous mycobacterial infections. These observations support the central role of the IL-12/IFN-γ pathway in controlling mycobacterial infection. In this review, we discuss the knowledge that associates both simple and complex inheritance with susceptibility to mycobacterial diseases. We place a special emphasis on monogenic disorders, since these clearly pinpoint pathways and can adduce mechanism. We also describe the clinical, immunological, and pathological features that may steer clinical investigation in the appropriate directions.