A protective and agonistic function of IL-12p40 in mycobacterial infection

C Hölscher, R A Atkinson, B Arendse, N Brown, E Myburgh, G Alber, Frank Brombacher

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IL-12p35(-/-)p40(-/-) mice are highly susceptible to Mycobacterium bovis bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis infection. In this study IL-12p35(-/-) mice, which are able to produce endogenous IL-12p40, cleared M. bovis BCG and showed reduced susceptibility to pulmonary M. tuberculosis infection, which was in striking contrast to the outcome of mycobacterial infection in IL-12p35(-/-)p40(-/-) mice. Resistance in wild-type and IL-12p35(-/-) mice was accompanied by protective granuloma formation and Ag-specific delayed-type hypersensitivity responses, which were impaired in susceptible IL-12p35(-/- )p40(-/-) mice. Furthermore, IL-12p35(-/-) mice, but not IL-12p35(-/-)p40(-/-) mice, mounted Ag-specific Th1 and cytotoxic T cell responses. In vivo therapy with rIL-12p40 homodimer restored the impaired delayed-type hypersensitivity responses in M. bovis BCG-infected IL-12p35(-/-)p40(-/-) mice and reverted them to a more resistant phenotype. Together, these results show evidence for a protective and agonistic role of endogenous and exogenous IL-12p40 in mycobacterial infection, which is independent of IL-12p70.

Original languageEnglish
Pages (from-to)6957-66
Number of pages10
JournalJournal of Immunology
Issue number12
Publication statusPublished - 15 Dec 2001


  • Animals
  • Antigens, Bacterial/immunology
  • Cells, Cultured
  • Colony Count, Microbial
  • Granuloma/immunology
  • Hypersensitivity, Delayed/immunology
  • Interleukin-12/genetics
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins/biosynthesis
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mycobacterium bovis/growth & development
  • Mycobacterium tuberculosis/growth & development
  • Protein Subunits
  • Survival Rate
  • T-Lymphocytes, Cytotoxic/immunology
  • Th1 Cells/immunology
  • Tuberculosis, Pulmonary/drug therapy

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