Understanding the genetic basis of susceptibility to mycobacterial infection

Genetic factors have long been suspected of determining susceptibility and resistance to mycobacterial infection. The recent identification of families with a unique susceptibility to mycobacterial infection, and the identification of mutations in the genes for either the interferon-gamma (IFN-gamma) receptor or the interleukin (IL)-12 receptor as the cause of the defect, has provided an important clue to the pathways critical for resistance to mycobacterial infection in humans. Although the genetically determined absence of key cytokines or their receptors results in susceptibility to lethal mycobacterial infections in early childhood, it is likely that more subtle mutations that result in only partial dysfunction of macrophage upregulation pathways may play a role in susceptibility to tuberculosis (TB) and leprosy in the general population.