Mycobacterial diseases in patients with inborn errors of immunity

Clinical disease caused by the agent of tuberculosis, Mycobacterium tuberculosis, and by less virulent mycobacteria, such as bacillus Calmette-Guerin (BCG) vaccines and environmental mycobacteria, can result from inborn errors of immunity (IEIs). IEIs underlie more than 450 conditions, each associated with an impairment of the development and/or function of hematopoietic and/or non-hematopoietic cells involved in host defense. Only a minority of IEIs confer predisposition to mycobacterial disease. The IEIs underlying susceptibility to bona fide tuberculosis are less well delineated than those responsible for susceptibility to less virulent mycobacteria. However, all these IEIs share a defining feature: the impairment of immunity mediated by interferon gamma (IFN-gamma). More profound IFN-gamma deficiency is associated with a greater vulnerability to weakly virulent mycobacteria, whereas more selective IFN-gamma deficiency is associated with a more selective predisposition to mycobacterial disease. We review here recent progress in the study of IEIs underlying mycobacterial diseases.

Automated summary

Clinical diseases caused by Mycobacterium tuberculosis, BCG vaccines, and environmental mycobacteria can result from inborn errors of immunity (IEIs). These IEIs are associated with impairments in the development and/or function of cells involved in host defense. Vulnerability to mycobacterial diseases is associated with IFN-gamma deficiency, with different levels of deficiency leading to different susceptibilities to mycobacteria.