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Science 29 May 1998:
Vol. 280. no. 5368, pp. 1435 - 1438
DOI: 10.1126/science.280.5368.1435
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Reports

Severe Mycobacterial and Salmonella Infections in Interleukin-12 Receptor-Deficient Patients

Rolien de Jong, Frédéric Altare, Inez-Anne Haagen, Diënne G. Elferink, Tjitske de Boer, Peter J. C. van Breda Vriesman, Peter J. Kabel, Johannes M. T. Draaisma, Jaap T. van Dissel, Frank P. Kroon, Jean-Laurent Casanova, Tom H. M. Ottenhoff *

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 beta 1/beta 2 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-12Rbeta 1 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-12Rbeta 1 sequence analysis revealed genetic mutations that resulted in premature stop codons in the extracellular domain. The lack of IL-12Rbeta 1 expression results in a human immunodeficiency and shows the essential role of IL-12 in resistance to infections due to intracellular bacteria.

R. de Jong, D. G. Elferink, T. de Boer, T. H. M. Ottenhoff, Department of Immunohematology and Bloodbank, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands.
F. Altare and J-L. Casanova, INSERM Unité 429, Hôpital Necker-Enfants Malades,149, Rue de Sevres, 75743 Paris Cedez 15, France.
I.-A. Haagen and P. J. C. van Breda Vriesman, Department of Immunology, University Hospital Maastricht, P.O. Box 5800, 6202 AZ Maastricht, the Netherlands.

P. J. Kabel and J. M. T. Draaisma, Department of Medical Microbiology and Immunology, and Department of Pediatrics, St. Elisabeth Hospital, P.O. Box 747, 5000 AS Tilburg, the Netherlands.
J. T. van Dissel and F. P. Kroon, Department of Infectious Diseases, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, the Netherlands.
*   To whom correspondence should be addressed. E-mail: ihbsecr{at}euronet.nl

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J. Immunol. 169, 3900-3907
   Abstract »    Full Text »    PDF »
STAT4 serine phosphorylation is critical for IL-12-induced IFN-gamma production but not for cell proliferation.
A. Morinobu, M. Gadina, W. Strober, R. Visconti, A. Fornace, C. Montagna, G. M. Feldman, R. Nishikomori, and J. J. O'Shea (2002)
PNAS 99, 12281-12286
   Abstract »    Full Text »    PDF »
Toll-Like Receptor 4 Expression Is Required to Control Chronic Mycobacterium tuberculosis Infection in Mice.
B. Abel, N. Thieblemont, V. J. F. Quesniaux, N. Brown, J. Mpagi, K. Miyake, F. Bihl, and B. Ryffel (2002)
J. Immunol. 169, 3155-3162
   Abstract »    Full Text »    PDF »
Investigation of Environmental and Host-related Risk Factors for Tuberculosis in Africa. I. Methodological Aspects of a Combined Design.
C. Lienhardt, S. Bennett, G. Del Prete, O. Bah-Sow, M. Newport, P. Gustafson, K. Manneh, V. Gomes, A. Hill, and K. McAdam (2002)
Am. J. Epidemiol. 155, 1066-1073
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Investigation of Environmental and Host-related Risk Factors for Tuberculosis in Africa. II. Investigation of Host Genetic Factors.
S. Bennett, C. Lienhardt, O. Bah-Sow, P. Gustafson, K. Manneh, G. Del Prete, V. Gomes, M. Newport, K. McAdam, and A. Hill (2002)
Am. J. Epidemiol. 155, 1074-1079
   Abstract »    Full Text »    PDF »
Reduced Expression of STAT4 and IFN-{gamma} in Macrophages from BALB/c Mice.
E. Kuroda, T. Kito, and U. Yamashita (2002)
J. Immunol. 168, 5477-5482
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Mycobacterium tuberculosis Induces Differential Cytokine Production from Dendritic Cells and Macrophages with Divergent Effects on Naive T Cell Polarization.
S. P. Hickman, J. Chan, and P. Salgame (2002)
J. Immunol. 168, 4636-4642
   Abstract »    Full Text »    PDF »
Human cytomegalovirus inhibits maturation and impairs function of monocyte-derived dendritic cells.
M. Moutaftsi, A. M. Mehl, L. K. Borysiewicz, and Z. Tabi (2002)
Blood 99, 2913-2921
   Abstract »    Full Text »    PDF »
Innate Immunity to Mycobacterium tuberculosis.
R. van Crevel, T. H. M. Ottenhoff, and J. W. M. van der Meer (2002)
Clin. Microbiol. Rev. 15, 294-309
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Coexpression of Interleukin-12 Chains by a Self-Splicing Vector Increases the Protective Cellular Immune Response of DNA and Mycobacterium bovis BCG Vaccines against Mycobacterium tuberculosis.
U. Palendira, A. T. Kamath, C. G. Feng, E. Martin, P. J. Chaplin, J. A. Triccas, and W. J. Britton (2002)
Infect. Immun. 70, 1949-1956
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Transmembrane TNF Induces an Efficient Cell-Mediated Immunity and Resistance to Mycobacterium bovis Bacillus Calmette-Guerin Infection in the Absence of Secreted TNF and Lymphotoxin-{alpha}.
M. L. Olleros, R. Guler, N. Corazza, D. Vesin, H.-P. Eugster, G. Marchal, P. Chavarot, C. Mueller, and I. Garcia (2002)
J. Immunol. 168, 3394-3401
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Mycobacterium bovis Vertebral Osteomyelitis as a Complication of Intravesical BCG Use.
R. Abu-Nader and C. L. Terrell (2002)
Mayo Clin. Proc. 77, 393-397
   Abstract »    PDF »
Macrophage defences against respiratory tract infections: The immunology of childhood respiratory infections.
S B Gordon and R C Read (2002)
Br. Med. Bull. 61, 45-61
   Abstract »    Full Text »    PDF »
Dendritic Cells Are Host Cells for Mycobacteria In Vivo That Trigger Innate and Acquired Immunity.
X. Jiao, R. Lo-Man, P. Guermonprez, L. Fiette, E. Deriaud, S. Burgaud, B. Gicquel, N. Winter, and C. Leclerc (2002)
J. Immunol. 168, 1294-1301
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Inability of IL-12 to Down-Regulate IgE Synthesis Due to Defective Production of IFN-{gamma} in Atopic NC/Nga Mice.
M. Matsumoto, A. Itakura, A. Tanaka, C. Fujisawa, and H. Matsuda (2001)
J. Immunol. 167, 5955-5962
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Tuberculosis Associated with Infliximab, a Tumor Necrosis Factor {alpha}-Neutralizing Agent.
J. Keane, S. Gershon, R. P. Wise, E. Mirabile-Levens, J. Kasznica, W. D. Schwieterman, J. N. Siegel, and M. M. Braun (2001)
N. Engl. J. Med. 345, 1098-1104
   Abstract »    Full Text »    PDF »
IL-1{beta} induces dendritic cells to produce IL-12.
A. K. Wesa and A. Galy (2001)
Int. Immunol. 13, 1053-1061
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A Role for IL-12 Receptor Expression and Signal Transduction in Host Defense in Leprosy.
J. Kim, K. Uyemura, M. K. Van Dyke, A. J. Legaspi, T. H. Rea, K. Shuai, and R. L. Modlin (2001)
J. Immunol. 167, 779-786
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Impairment of Mycobacterial But Not Viral Immunity by a Germline Human STAT1 Mutation.
S. Dupuis, C. Dargemont, C. Fieschi, N. Thomassin, S. Rosenzweig, J. Harris, S. M. Holland, R. D. Schreiber, and J.-L. Casanova (2001)
Science 293, 300-303
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Infection of Human Macrophages and Dendritic Cells with Mycobacterium tuberculosis Induces a Differential Cytokine Gene Expression That Modulates T Cell Response.
E. Giacomini, E. Iona, L. Ferroni, M. Miettinen, L. Fattorini, G. Orefici, I. Julkunen, and E. M. Coccia (2001)
J. Immunol. 166, 7033-7041
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Mannosylated Lipoarabinomannans Inhibit IL-12 Production by Human Dendritic Cells: Evidence for a Negative Signal Delivered Through the Mannose Receptor.
J. Nigou, C. Zelle-Rieser, M. Gilleron, M. Thurnher, and G. Puzo (2001)
J. Immunol. 166, 7477-7485
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Culture at High Density Improves the Ability of Human Macrophages to Control Mycobacterial Growth.
N. Boechat, F. Bouchonnet, M. Bonay, A. Grodet, V. Pelicic, B. Gicquel, and A. J. Hance (2001)
J. Immunol. 166, 6203-6211
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A Heritable Defect in IL-12 Signaling in B10.Q/J Mice. II. Effect on Acute Resistance to Toxoplasma gondii and Rescue by IL-18 Treatment.
G. S. Yap, R. Ortmann, E. Shevach, and A. Sher (2001)
J. Immunol. 166, 5720-5725
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Missense mutation of the interleukin-12 receptor {beta}1 chain-encoding gene is associated with impaired immunity against Mycobacterium avium complex infection.
T. Sakai, M. Matsuoka, M. Aoki, K. Nosaka, and H. Mitsuya (2001)
Blood 97, 2688-2694
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Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta.
C. Manca, L. Tsenova, A. Bergtold, S. Freeman, M. Tovey, J. M. Musser, C. E. Barry III, V. H. Freedman, and G. Kaplan (2001)
PNAS
   Abstract »    Full Text »
Genetics of Susceptibility to Infectious Diseases: Tuberculosis and Leprosy as Examples.
S. Marquet and E. Schurr (2001)
Drug Metab. Dispos. 29, 479-483
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