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 Chackerian, A. A.
Right arrow Articles by Bowman, E. P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Chackerian, A. A.
Right arrow Articles by Bowman, E. P.

 Previous Article  |  Next Article 

Infection and Immunity, November 2006, p. 6092-6099, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00621-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Neutralization or Absence of the Interleukin-23 Pathway Does Not Compromise Immunity to Mycobacterial Infection{triangledown}

Alissa A. Chackerian,1 Shi-Juan Chen,1 Scott J. Brodie,2 Jeanine D. Mattson,3 Terrill K. McClanahan,3 Robert A. Kastelein,1 and Edward P. Bowman1*

Discovery Research,1 Experimental Pathology and Pharmacology, Schering-Plough Biopharma, 901 California Ave., Palo Alto, California 94304-1104,3 Department of Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, New Jersey 078482

Received 18 April 2006/ Returned for modification 2 June 2006/ Accepted 8 August 2006

Interleukin-23 (IL-23), a member of the IL-12 family, is a heterodimeric cytokine that is composed of the p40 subunit of IL-12 plus a unique p19 subunit. IL-23 is critical for autoimmune inflammation, in part due to its stimulation of the proinflammatory cytokine IL-17A. It is less clear, however, if IL-23 is required during the immune response to pathogens. We examined the role of IL-23 during Mycobacterium bovis BCG infection. We found that IL-23 reduces the bacterial burden and promotes granuloma formation when IL-12 is absent. However, IL-23 does not contribute substantially to host resistance when IL-12 is present, as the ability to control bacterial growth and form granulomata is not affected in IL-23p19-deficient mice and mice treated with a specific anti-IL-23p19 antibody. IL-23p19-deficient mice are also able to mount an effective memory response to secondary infection with BCG. While IL-23p19-deficient mice do not produce IL-17A, this cytokine is not necessary for effective control of infection, and antibody blocking of IL-17A in both wild-type and IL-12-deficient mice also has little effect on the bacterial burden. These data suggest that IL-23 by itself does not play an essential role in the protective immune response to BCG infection; however, the presence of IL-23 can partially compensate for the absence of IL-12. Furthermore, neutralization of IL-23 or IL-17A does not increase susceptibility to mycobacterial BCG infection.

* Corresponding author. Mailing address: 901 California Ave., Palo Alto, CA 94304-1104. Phone: (650) 496-1249. Fax: (650) 496-1200. E-mail: eddie.bowman{at}spcorp.com.

{triangledown} Published ahead of print on 21 August 2006.

Editor: J. L. Flynn

Infection and Immunity, November 2006, p. 6092-6099, Vol. 74, No. 11
0019-9567/06/$08.00+0     doi:10.1128/IAI.00621-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Wan, Y. Y., Flavell, R. A. (2009). How Diverse--CD4 Effector T Cells and their Functions. J Mol Cell Biol 1: 20-36 [Abstract] [Full Text]  
  • Jang, M. S., Son, Y. M., Kim, G. R., Lee, Y. J., Lee, W. K., Cha, S. H., Han, S. H., Yun, C.-H. (2009). Synergistic production of interleukin-23 by dendritic cells derived from cord blood in response to costimulation with LPS and IL-12. J. Leukoc. Biol. 86: 691-699 [Abstract] [Full Text]  
  • Schulz, S. M., Kohler, G., Schutze, N., Knauer, J., Straubinger, R. K., Chackerian, A. A., Witte, E., Wolk, K., Sabat, R., Iwakura, Y., Holscher, C., Muller, U., Kastelein, R. A., Alber, G. (2008). Protective Immunity to Systemic Infection with Attenuated Salmonella enterica serovar Enteritidis in the Absence of IL-12 Is Associated with IL-23-Dependent IL-22, but Not IL-17. J. Immunol. 181: 7891-7901 [Abstract] [Full Text]  
  • Montufar-Solis, D., Schaefer, J., Hicks, M. J., Klein, J. R. (2008). Massive but selective cytokine dysregulation in the colon of IL-10 / mice revealed by multiplex analysis. Int Immunol 20: 141-154 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»