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

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.