title: Host genetic factors in susceptibility to mycobacterial disease.
abstract: Primary immunodeficiencies (PID) are a group of rare inherited disorders that manifest as heightened susceptibility to infection, autoimmunity and/or malignancy. By exploring their genetic and cellular aetiology, we can learn much about the basis of pathogen-specific immunity in humans. This is exemplified by mycobacterial susceptibility, which occurs across several types of PID, either as an isolated problem or as part of a broader pattern of susceptibility to infection. These experiments of nature have contributed to our understanding of the central role of T cells in activating infected macrophages to eliminate phagosomal mycobacteria through mutually activating, cytokine-dependent interactions. In recent years, the discovery of novel forms of PID has emphasised the important role of dendritic cells and monocytes in mycobacterial defence in humans. Here, we provide a brief overview of these new disorders alongside other genetic causes of susceptibility to mycobacterial disease.
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK, and Great North Children's Hospital, Newcastle-upon-Tyne, UK.
authors.forename: Christopher J A
authors.initials: CJ
authors.lastname: Duncan
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle-upon-Tyne, UK, and Department of Infection and Tropical Medicine Royal Victoria Infirmary, Newcastle-upon-Tyne, UK sophie.hambleton@ncl.ac.uk.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hambleton
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics*; D008875:Middle Aged; D009164:Mycobacterium Infections / Q000235:genetics*; D055815:Young Adult
keywords: BCG; Mycobacteria; dendritic cell; human genetics; primary immunodeficiency; tuberculosis