Host genetic factors in susceptibility to mycobacterial disease

Abstract

Primary immunodefi ciencies (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-specifi c immunity in humans. This is exemplifi ed 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.