Why do some individuals develop clinical disease after exposure to mycobacteria, while others remain healthy? This review explores the genetic basis of immunity to mycobacteria in humans, combining insights from mouse immunology with the methods of human genetics. It highlights the unique advantages of studying natural mycobacterial infections in humans, which are not fully replicated in animal models. The review discusses Mendelian disorders that increase vulnerability to BCG and other mycobacteria, as well as genetic polymorphisms associated with leprosy and tuberculosis in the general population. While causal vulnerability genes remain largely unidentified, these studies offer valuable insights into protective immunity. By integrating microbiological, clinical, and genetic data, this research lays the foundation for understanding the complex interplay between human genes and mycobacterial infections, potentially serving as a model for studying immunity to other infectious agents.
Published in the Annual Review of Immunology, this paper aligns with the journal's focus on comprehensive reviews of significant topics in immunology. The review synthesizes current knowledge on the genetic basis of immunity to mycobacteria, making it highly relevant to the journal's scope.