Abstract
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 language | English |
|---|---|
| Pages (from-to) | 6957-66 |
| Number of pages | 10 |
| Journal | Journal of Immunology |
| Volume | 167 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 15 Dec 2001 |
Keywords
- 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