IAI FigSearch
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Thompson-Snipes, L.
Right arrow Articles by Radzioch, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Thompson-Snipes, L.
Right arrow Articles by Radzioch, D.

 Previous Article  |  Next Article 

Infection and Immunity, November 1998, p. 5268-5274, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Acquired Resistance but Not Innate Resistance to Mycobacterium bovis Bacillus Calmette-Guérin Is Compromised by Interleukin-12 Ablation

LuAnn Thompson-Snipes,* Emil Skamene, and Danuta Radzioch

Montreal General Hospital Research Institute and McGill University, Montreal, Quebec, Canada

Received 7 May 1998/Returned for modification 15 June 1998/Accepted 7 August 1998

Interleukin-12 (IL-12) is one of the first cytokines produced by macrophages, key mediators of innate resistance, during the host's immune response to infections. Therefore, in this study we propose that IL-12 has an important role in the early phase of the immune response to Mycobacterium bovis BCG. IL-12 has been shown to enhance the maturation of protective Th1 cells and gamma interferon (IFN-gamma ) production during mycobacterial infection. Therefore, it may play a crucial role during the immune phase of infection as well. To examine the role of IL-12 in both the innate and the immune phase of infection, we compared BCG-resistant mice, B10.A (Bcgr), to the susceptible congenic strain B10.A (Bcgs) following administration of a blocking monoclonal antibody to IL-12 (10F6). Anti-IL-12-treated susceptible animals exhibited a two- to threefold increase in spleen CFU by day 21. In contrast, anti-IL-12 treatment had little or no effect on the response of the genetically resistant animals to infection. The B10.A (Bcgr) but not the B10.A (Bcgs) mice had an increase in IFN-gamma mRNA relative to baseline levels as early as day 1 of infection irrespective of anti-IL-12 treatment. By day 14, B10.A (Bcgr) mice showed a decrease in IFN-gamma mRNA while the B10.A (Bcgs) mice showed a significant increase in IFN-gamma mRNA levels. Thus, during BCG infection, the B10.A (Bcgr) mice mount an early IFN-gamma response against BCG whereas the B10.A (Bcgs) mice have a delayed IFN-gamma response correlating with their genetic permissiveness expressed as an increased mycobacterial load by day 21. Overall, our data demonstrate that the inherent resistance of B10.A (Bcgr) mice to mycobacteria does not depend on optimal levels of IL-12 to maintain effective control of the bacteria, whereas IL-12 is important for the susceptible animals' response to BCG during the peak of infection.

* Corresponding author. Mailing address: Centre for Host Resistance, Montreal General Hospital Research Institute, 1650 Cedar Ave., Room LH-11-218, Montreal, QC, Canada H3G 1A4. Phone: (514) 937-6011, ext. 4515. Fax: (514) 934-8260. E-mail: lsnipes{at}is.mgh.mcgill.ca.

Infection and Immunity, November 1998, p. 5268-5274, Vol. 66, No. 11
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 1998 by the American Society for Microbiology. All rights reserved.