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. Thus, IL-12-dependent IFN-gamma secretion in humans seems essential in the control of mycobacterial infections, despite the formation of mature granulomas due to IL-12-independent IFN-gamma secretion.
Altare
F
F
INSERM U429, Hôpital Necker-Enfants Malades, Paris 75015, France.
Durandy
A
A
Lammas
D
D
Emile
J F
JF
Lamhamedi
S
S
Le Deist
F
F
Drysdale
P
P
Jouanguy
E
E
Döffinger
R
R
Bernaudin
F
F
Jeppsson
O
O
Gollob
J A
JA
Meinl
E
E
Segal
A W
AW
Fischer
A
A
Kumararatne
D
D
Casanova
J L
JL
D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D006099:Granuloma / Q000276:immunology; D006801:Humans; D006968:Hypersensitivity, Delayed; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D015270:Mycobacterium avium-intracellulare Infection / Q000276:immunology*; D009163:Mycobacterium bovis; D010375:Pedigree; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000235:genetics*; D053707:Receptors, Interleukin-12; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology*; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D018664:Interleukin-12; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D000096743:Interferon gamma Receptor