| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Institute of Immunology, College of Veterinary Medicine, University of Leipzig, Leipzig, Germany;
Department of Drug Safety and Metabolism, Schering-Plough Research Institute, Lafayette, NJ 07848;
Institute of Neuropathology, Medical Faculty, University of Cologne, Cologne, Germany;
Gerhard Domagk Institute of Pathology, University of Muenster, Muenster, Germany;
¶ Experimental Pathology and Pharmacology, DNAX Research, Palo Alto, CA 94304; and
|| Discovery Research, DNAX Research, Palo Alto, CA 94304
IL-23, a heterodimeric cytokine composed of the p40 subunit of IL-12 and a novel p19 subunit, has been shown to be a key player in models of autoimmune chronic inflammation. To investigate the role of IL-23 in host resistance during chronic fungal infection, wild-type, IL-12- (IL-12p35–/–), IL-23- (IL-23p19–/–), and IL-12/IL-23- (p40-deficient) deficient mice on a C57BL/6 background were infected with Cryptococcus neoformans. Following infection, p40-deficient mice demonstrated higher mortality than IL-12p35–/– mice. Reconstitution of p40-deficient mice with rIL-23 prolonged their survival to levels similar to IL-12p35–/– mice. IL-23p19–/– mice showed a moderately reduced survival time and delayed fungal clearance in the liver. Although IFN-
production was similar in wild-type and IL-23p19–/– mice, production of IL-17 was strongly impaired in the latter. IL-23p19–/– mice produced fewer hepatic granulomata relative to organ burden and showed defective recruitment of mononuclear cells to the brain. Moreover, activation of microglia cells and expression of IL-1
, IL-6, and MCP-1 in the brain was impaired. These results show that IL-23 complements the more dominant role of IL-12 in protection against a chronic fungal infection by an enhanced inflammatory cell response and distinct cytokine regulation.
This article has been cited by other articles:
|
|
 |
|
  F. Gerosa, B. Baldani-Guerra, L. A. Lyakh, G. Batoni, S. Esin, R. T. Winkler-Pickett, M. R. Consolaro, M. De Marchi, D. Giachino, A. Robbiano, et al. Differential regulation of interleukin 12 and interleukin 23 production in human dendritic cells J. Exp. Med., June 9, 2008; 205(6): 1447 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. F. Y. Cheung, C. K. Wong, and C. W. K. Lam Molecular Mechanisms of Cytokine and Chemokine Release from Eosinophils Activated by IL-17A, IL-17F, and IL-23: Implication for Th17 Lymphocytes-Mediated Allergic Inflammation J. Immunol., April 15, 2008; 180(8): 5625 - 5635. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Smith, A. Zarbock, M. A. Stark, T. L. Burcin, A. C. Bruce, P. Foley, and K. Ley IL-23 Is Required for Neutrophil Homeostasis in Normal and Neutrophilic Mice J. Immunol., December 15, 2007; 179(12): 8274 - 8279. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Muller, W. Stenzel, G. Kohler, C. Werner, T. Polte, G. Hansen, N. Schutze, R. K. Straubinger, M. Blessing, A. N. J. McKenzie, et al. IL-13 Induces Disease-Promoting Type 2 Cytokines, Alternatively Activated Macrophages and Allergic Inflammation during Pulmonary Infection of Mice with Cryptococcus neoformans J. Immunol., October 15, 2007; 179(8): 5367 - 5377. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Butchar, M. V. S. Rajaram, L. P. Ganesan, K. V. L. Parsa, C. D. Clay, L. S. Schlesinger, and S. Tridandapani Francisella tularensis Induces IL-23 Production in Human Monocytes J. Immunol., April 1, 2007; 178(7): 4445 - 4454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Umemura, A. Yahagi, S. Hamada, M. D. Begum, H. Watanabe, K. Kawakami, T. Suda, K. Sudo, S. Nakae, Y. Iwakura, et al. IL-17-Mediated Regulation of Innate and Acquired Immune Response against Pulmonary Mycobacterium bovis Bacille Calmette-Guerin Infection J. Immunol., March 15, 2007; 178(6): 3786 - 3796. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Chackerian, S.-J. Chen, S. J. Brodie, J. D. Mattson, T. K. McClanahan, R. A. Kastelein, and E. P. Bowman Neutralization or Absence of the Interleukin-23 Pathway Does Not Compromise Immunity to Mycobacterial Infection Infect. Immun., November 1, 2006; 74(11): 6092 - 6099. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
