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Interferon-gamma and interleukin-12 pathway defects and human disease
1Laboratory of Host Defenses, National Institutes of Health, NIAID, Building 10, Room 11N103, 10 Center Dr, MSC 1886, Bethesda, MD 20892, USA.
Abstract:
A genetic component to human mycobacterial disease susceptibility has long been postulated. Over the past five years, mutations in the interferon-gamma (IFNgamma) receptor, IL-12 receptor beta1 (IL-12Rbeta1), and IL-12 p40 genes have been recognized. These mutations are associated with heightened susceptibility to disease caused by intracellular pathogens including nontuberculous mycobacteria, vaccine-associated bacille Calmette Guerin (BCG), Salmonella species, and some viruses. We describe the genotype-phenotype correlations in IFNgamma receptor, IL-12Rbeta1, and IL-12 p40 deficiency, and discuss how study of these diseases has enhanced knowledge of human host defense against mycobacteria and other intracellular pathogens.
Insights
Genetic mutations in interferon-gamma (IFNgamma) receptor and IL-12 pathway genes increase susceptibility to mycobacterial diseases. Studying these genetic deficiencies enhances understanding of host defense against intracellular pathogens.
Area of Science:
- Immunology
- Genetics
- Infectious Diseases
Background:
- Human susceptibility to mycobacterial diseases has long been suspected to have a genetic basis.
- Recent discoveries have identified specific gene mutations contributing to this susceptibility.
Purpose of the Study:
- To describe genotype-phenotype correlations in deficiencies of the interferon-gamma (IFNgamma) receptor, IL-12 receptor beta1 (IL-12Rbeta1), and IL-12 p40 genes.
- To discuss how studying these genetic diseases advances knowledge of human host defense against mycobacteria and other intracellular pathogens.
Main Methods:
- Review of genotype-phenotype correlations in patients with genetic deficiencies.
- Analysis of susceptibility to intracellular pathogens in relation to specific gene mutations.
Main Results:
- Mutations in IFNgamma receptor, IL-12Rbeta1, and IL-12 p40 genes are linked to increased susceptibility to mycobacterial and other intracellular infections.
- These deficiencies manifest in heightened vulnerability to diseases caused by nontuberculous mycobacteria, BCG, Salmonella, and certain viruses.
Conclusions:
- Genetic factors play a crucial role in determining susceptibility to mycobacterial diseases.
- Understanding these genetic deficiencies provides critical insights into the mechanisms of human host defense against a range of intracellular pathogens.