Inherited interleukin 12 deficiency in a child with bacille Calmette-Guérin and Salmonella enteritidis disseminated infection.

Interferon-gamma receptor ligand-binding chain (IFN-gammaR1) or signaling chain (IFN-gammaR2) deficiency, like interleukin 12 receptor beta1 chain (IL-12Rbeta1) deficiency, predispose to severe infections due to poorly virulent mycobacteria and salmonella. A child with bacille Calmette-Guérin and Salmonella enteritidis infection was investigated. Mutations in the genes for IFN-gammaR1, IFN-gammaR2, IL-12Rbeta1, and other molecules implicated in IL-12- or IFN-gamma-mediated immunity were sought.

Interferon-gamma receptor deficiency: relationship between genotype, environment, and phenotype (Review).

Interferon-gamma receptor ligand binding chain (IFNgammaR1) deficiency is an autosomal recessive inherited immune disorder. Mutations in the IFNgR1 gene are associated with severe infections due to mycobacteria. However, several aspects of the phenotype of IFNgammaR1-deficient children have recently been found to vary from case to case.

Mendelian susceptibility to mycobacterial infection in man.

Selective susceptibility to poorly pathogenic mycobacteria, such as bacille Calmette-Guérin vaccine and environmental non-tuberculous mycobacteria, has long been suspected to be a mendelian disorder but its molecular basis has remained elusive. Recently, recessive mutations in the interferon-gamma-receptor receptor ligand-binding chain, interferon-gamma-receptor signalling chain, IL-12 p40 subunit and IL-12-receptor beta 1 chain genes have been identified in a number of patients with disseminated mycobacterial infection. Although genetically distinct, these conditions are immunologically related and highlight the essential role of interferon-gamma-mediated immunity in the control of mycobacteria in man.

Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency.

In humans, interferon gamma (IFN-gamma) receptor deficiency leads to a predisposition to mycobacterial infections and impairs the formation of mature granulomas. Interleukin-12 (IL-12) receptor deficiency was found in otherwise healthy individuals with mycobacterial infections. Mature granulomas were seen, surrounded by T cells and centered with epithelioid and multinucleated giant cells, yet reduced IFN-gamma concentrations were found to be secreted by activated natural killer and T cells.

Fatal disseminated Mycobacterium smegmatis infection in a child with inherited interferon gamma receptor deficiency.

Mycobacterium smegmatis is a common environmental mycobacterium that was first identified in 1884, yet is a rare pathogen in humans. The few M. smegmatis infections reported to date have been localized and have occurred in association with a primary lesion in otherwise immunocompetent individuals.