title: Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients.
abstract: Interleukin-12 (IL-12) is a cytokine that promotes cell-mediated immunity to intracellular pathogens by inducing type 1 helper T cell (TH1) responses and interferon-gamma (IFN-gamma) production. IL-12 binds to high-affinity beta1/beta2 heterodimeric IL-12 receptor (IL-12R) complexes on T cell and natural killer cells. Three unrelated individuals with severe, idiopathic mycobacterial and Salmonella infections were found to lack IL-12Rbeta1 chain expression. Their cells were deficient in IL-12R signaling and IFN-gamma production, and their remaining T cell responses were independent of endogenous IL-12. IL-12Rbeta1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.
authors.affiliation: Department of Immunohematology and Bloodbank, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: de Jong
authors.forename: F
authors.initials: F
authors.lastname: Altare
authors.forename: I A
authors.initials: IA
authors.lastname: Haagen
authors.forename: D G
authors.initials: DG
authors.lastname: Elferink
authors.forename: T
authors.initials: T
authors.lastname: Boer
authors.forename: P J
authors.initials: PJ
authors.lastname: van Breda Vriesman
authors.forename: P J
authors.initials: PJ
authors.lastname: Kabel
authors.forename: J M
authors.initials: JM
authors.lastname: Draaisma
authors.forename: J T
authors.initials: JT
authors.lastname: van Dissel
authors.forename: F P
authors.initials: FP
authors.lastname: Kroon
authors.forename: J L
authors.initials: JL
authors.lastname: Casanova
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
mesh_terms: D000328:Adult; D002675:Child, Preschool; D018388:Codon, Terminator; D004198:Disease Susceptibility; D005260:Female; D016368:Frameshift Mutation; D005808:Genes, Recessive; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D009154:Mutation; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*; D009163:Mycobacterium bovis; D017471:Receptors, Interferon / Q000378:metabolism; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D053707:Receptors, Interleukin-12; D012480:Salmonella Infections / Q000276:immunology*; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D018388:Codon, Terminator; D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D000096743:Interferon gamma Receptor; C508438:IL12RB1 protein, human; C508439:IL12RB2 protein, human