Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance.

Détails

ID Serval
serval:BIB_7CD5B0072E6A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guérin and Mycobacterium tuberculosis clearance.
Périodique
Immunology
Auteur(s)
Olleros M.L., Vesin D., Martinez-Soria E., Allenbach C., Tacchini-Cottier F., Pache J.C., Marchal G., Rahman J., Fernández C., Izui S., Garcia I.
ISSN
0019-2805 (Print)
ISSN-L
0019-2805
Statut éditorial
Publié
Date de publication
2007
Volume
122
Numéro
3
Pages
350-361
Langue
anglais
Résumé
Interleukin (IL)-12p40, a subunit of IL-12p70 and IL-23, has previously been shown to inhibit IL-12p70 activity and interferon-gamma (IFN-gamma) production. However, recent evidence has suggested that the role of IL-12p40 is more complex. To study the contribution of IL-12p40 to immune responses against mycobacterial infections, we have used transgenic (tg) mice overexpressing IL-12p40 under the control of a major histocompatibility complex-II promoter. The IL-12p40 transgene was expressed during steady state at concentrations of 129 +/- 25 ng/ml of serum and 75 +/- 13 ng per spleen, while endogenous IL-12p40 was hardly detectable in control littermates. Bacille Calmette-Guérin (BCG) infection strongly induced the expression of IL-12p40 transgene in infected organs, and IL-12p40 monomeric and dimeric forms were identified in spleen of IL-12p40 tg mice. Excessive production of IL-12p40 resulted in a 14-fold increase in IL-12p70 serum levels in tg mice versus non-transgenic mice. IL-23 was also strongly elevated in the serum and spleens of IL-12p40 tg mice through BCG infection. While IFN-gamma and tumour necrosis factor protein levels were similar in IL-12p40 tg and non-transgenic mice, Th2 type immune responses were reduced in IL-12p40 tg mice. The number of BCG granulomas and macrophage expressing inducible nitric oxide synthase were similar in IL-12p40 tg and non-transgenic mice. IL-12p40 tg mice were as resistant as non-transgenic mice to BCG and Mycobacterium tuberculosis infections as they could efficiently control bacillary growth. These data show that high amounts of IL-12p40 promotes IL-12p70 and IL-23 formation, but that does not affect T helper 1 type immune responses and granuloma function, thus leading to normal mycobacterial clearance in infected organs.
Mots-clé
Animals, Chemokines/biosynthesis, Granuloma/immunology, Immunity, Cellular, Interferon-gamma/biosynthesis, Interleukin-12/biosynthesis, Interleukin-12 Subunit p40/biosynthesis, Interleukin-12 Subunit p40/immunology, Interleukin-23/biosynthesis, Liver Diseases/immunology, Mice, Mice, Inbred C57BL, Mice, Transgenic, Mycobacterium bovis/isolation & purification, Mycobacterium tuberculosis/isolation & purification, Nitric Oxide Synthase Type II/metabolism, Spleen/immunology, Th1 Cells/immunology, Th2 Cells/immunology, Tuberculosis/immunology, Tuberculosis/microbiology, Tumor Necrosis Factor-alpha/biosynthesis
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 16:09
Dernière modification de la notice
20/08/2019 15:38
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