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A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection
Open accessAbstract
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.
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Cited by
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Cua, D. J., Sherlock, J., Chen, Y., Murphy, C. A., Joyce, B., Seymour, B., Lucian, L., To, W., Kwan, S., Churakova, T., et al. (2003) · Nature · doi:10.1038/nature01355 · Cited by 2,906
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Metadata
- Authors
- Hölscher, C., Atkinson, R. A., Arendse, B., Brown, N., Myburgh, E., Alber, G., & Brombacher, F.
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2001-12
- Volume
- 167
- Issue
- 12
- Pages
- 6957-6966
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1509377507
- Cited by
- 229
- References
- 0
- FWCI
- 10.71
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Hölscher, C., Atkinson, R. A., Arendse, B., Brown, N., Myburgh, E., Alber, G., & Brombacher, F. (2001). A Protective and Agonistic Function of IL-12p40 in Mycobacterial Infection. The Journal of Immunology. https://doi.org/10.4049/jimmunol.167.12.6957
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