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 Rudner, X. L.
Right arrow Articles by Shellito, J. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rudner, X. L.
Right arrow Articles by Shellito, J. E.

 Previous Article  |  Next Article 

Infection and Immunity, June 2007, p. 3055-3061, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01329-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Interleukin-23 (IL-23)-IL-17 Cytokine Axis in Murine Pneumocystis carinii Infection{triangledown}

Xiaowen L. Rudner, Kyle I. Happel, Erana A. Young, and Judd E. Shellito*

Section of Pulmonary/Critical Care Medicine, LSU Health Sciences Center, New Orleans, Louisiana

Received 18 August 2006/ Returned for modification 6 October 2006/ Accepted 18 March 2007

Host defense mechanisms against Pneumocystis carinii are not fully understood. Previous work in the murine model has shown that host defense against infection is critically dependent upon host CD4+ T cells. The recently described Th17 immune response is predominantly a function of effector CD4+ T cells stimulated by interleukin-23 (IL-23), but whether these cells are required for defense against P. carinii infection is unknown. We tested the hypothesis that P. carinii stimulates the early release of IL-23, leading to increases in IL-17 production and lung effector CD4+ T-cell population that mediate clearance of infection. In vitro, stimulation of alveolar macrophages with P. carinii induced IL-23, and IL-23p19 mRNA was expressed in lungs of mice infected with this pathogen. To address the role of IL-23 in resistance to P. carinii, IL-23p19–/– and wild-type control C57BL/6 mice were infected and their fungal burdens and cytokine/chemokine responses were compared. IL-23p19–/– mice displayed transient but impaired clearance of infection, which was most apparent 2 weeks after inoculation. In confirmatory studies, the administration of either anti-IL-23p19 or anti-IL-17 neutralizing antibody to wild-type mice infected with P. carinii also caused increases in fungal burdens. IL-17 and the lymphocyte chemokines IP-10, MIG, MIP-1{alpha}, MIP-1β, and RANTES were decreased in the lungs of infected IL-23p19–/– mice in comparison to their levels in the lungs of wild-type mice. In IL-23p19–/– mice infected with P. carinii, there were fewer effector CD4+ T cells in the lung tissue. Collectively, these studies indicate that the IL-23-IL-17 axis participates in host defense against P. carinii.

* Corresponding author. Mailing address: Section of Pulmonary and Critical Care Medicine, Department of Medicine, LSU Health Sciences Center, 1901 Perdido Street, Suite 3205, New Orleans, LA 70112. Phone: (504) 568-4634. Fax: (504) 568-4295. E-mail: jshell{at}lsuhsc.edu

{triangledown} Published ahead of print on 2 April 2007.

Editor: J. L. Flynn

Infection and Immunity, June 2007, p. 3055-3061, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01329-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Brucklacher-Waldert, V., Steinbach, K., Lioznov, M., Kolster, M., Holscher, C., Tolosa, E. (2009). Phenotypical Characterization of Human Th17 Cells Unambiguously Identified by Surface IL-17A Expression. J. Immunol. 183: 5494-5501 [Abstract] [Full Text]  
  • Das, J., Ren, G., Zhang, L., Roberts, A. I., Zhao, X., Bothwell, A. L.M., Van Kaer, L., Shi, Y., Das, G. (2009). Transforming growth factor {beta} is dispensable for the molecular orchestration of Th17 cell differentiation. JEM 206: 2407-2416 [Abstract] [Full Text]  
  • Paidipally, P., Periasamy, S., Barnes, P. F., Dhiman, R., Indramohan, M., Griffith, D. E., Cosman, D., Vankayalapati, R. (2009). NKG2D-Dependent IL-17 Production by Human T Cells in Response to an Intracellular Pathogen. J. Immunol. 183: 1940-1945 [Abstract] [Full Text]  
  • Zhang, X., Gao, L., Lei, L., Zhong, Y., Dube, P., Berton, M. T., Arulanandam, B., Zhang, J., Zhong, G. (2009). A MyD88-Dependent Early IL-17 Production Protects Mice against Airway Infection with the Obligate Intracellular Pathogen Chlamydia muridarum. J. Immunol. 183: 1291-1300 [Abstract] [Full Text]  
  • Awasthi, A., Kuchroo, V. K. (2009). Th17 cells: from precursors to players in inflammation and infection. Int Immunol 21: 489-498 [Abstract] [Full Text]  
  • Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., Filler, S. G., Masso-Welch, P., Edgerton, M., Gaffen, S. L. (2009). Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. JEM 206: 299-311 [Abstract] [Full Text]  
  • Ruan, S., McKinley, L., Zheng, M., Rudner, X., D'Souza, A., Kolls, J. K., Shellito, J. E. (2008). Interleukin-12 and Host Defense against Murine Pneumocystis Pneumonia. Infect. Immun. 76: 2130-2137 [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»