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Interleukin‐12p40 overexpression promotes interleukin‐12p70 and interleukin‐23 formation but does not affect bacille Calmette–Guérin and Mycobacterium tuberculosis clearance
Author(s) -
Olleros Maria L.,
Vesin Dominique,
MartinezSoria Eduardo,
Allenbach Cindy,
TacchiniCottier Fabienne,
Pache JeanClaude,
Marchal Gilles,
Rahman Jubayer,
Fernández Carmen,
Izui Shozo,
Garcia Irene
Publication year - 2007
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2007.02646.x
Subject(s) - interleukin 12 , immune system , biology , transgene , spleen , immunology , interferon gamma , mycobacterium bovis , mycobacterium tuberculosis , interleukin 4 , genetically modified mouse , interleukin 10 , microbiology and biotechnology , tuberculosis , medicine , cytotoxic t cell , in vitro , gene , biochemistry , pathology
Summary Interleukin (IL)‐12p40, a subunit of IL‐12p70 and IL‐23, has previously been shown to inhibit IL‐12p70 activity and interferon‐γ (IFN‐γ) 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‐γ 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.