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Scientific article
English

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

Published inImmunology, vol. 122, no. 3, p. 350-361
Publication date2007
Abstract

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-Guerin (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.

Keywords
  • Animals
  • Chemokines/biosynthesis
  • Granuloma/immunology
  • Immunity, Cellular
  • Interferon-gamma/biosynthesis
  • Interleukin-12/*biosynthesis
  • Interleukin-12 Subunit p40/biosynthesis/*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/microbiology/pathology
  • Tumor Necrosis Factor-alpha/biosynthesis
Affiliation Not a UNIGE publication
Citation (ISO format)
OLLEROS, Maria et al. Interleukin-12p40 overexpression promotes interleukin-12p70 and interleukin-23 formation but does not affect bacille Calmette-Guerin and Mycobacterium tuberculosis clearance. In: Immunology, 2007, vol. 122, n° 3, p. 350–361. doi: 10.1111/j.1365-2567.2007.02646.x
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ISSN of the journal0019-2805
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