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 Cai, G.
Right arrow Articles by Hunter, C. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cai, G.
Right arrow Articles by Hunter, C. A.

 Previous Article  |  Next Article 

Infection and Immunity, December 2000, p. 6932-6938, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Interleukin-18 (IL-18) Enhances Innate IL-12-Mediated Resistance to Toxoplasma gondii

Guifang Cai,1 Robert Kastelein,2 and Christopher A. Hunter1,*

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania,1 and Department of Molecular Biology, DNAX Research Institute, Palo Alto, California2

Received 17 March 2000/Returned for modification 10 May 2000/Accepted 28 August 2000

Innate resistance to Toxoplasma gondii is dependent on the ability of interleukin-12 (IL-12) to stimulate natural killer (NK) cell production of gamma interferon (IFN-gamma ). Since IL-18 is a potent enhancer of IL-12-induced production of IFN-gamma by NK cells, SCID mice (which lack an adaptive immune response) were used to assess the role of IL-18 in innate resistance to T. gondii. Administration of anti-IL-18 to SCID mice infected with T. gondii resulted in an early reduction in serum levels of IFN-gamma but did not significantly decrease resistance to this infection. In contrast, administration of exogenous IL-18 to infected SCID mice resulted in increased production of IFN-gamma , reduced parasite burden, and a delay in time to death. The protective effects of IL-18 treatment correlated with increased NK cell numbers and cytotoxic activity at the local site of administration and with elevated levels of inducible nitrous oxide synthose in the spleens of treated mice. In addition, in vivo depletion studies demonstrated that the ability of exogenous IL-18 to enhance resistance to T. gondii was dependent on IL-12, IFN-gamma , and NK cells. Together, these studies demonstrate that although endogenous IL-18 appears to have a limited role in innate resistance to T. gondii, treatment with IL-18 can augment NK cell-mediated immunity to this pathogen.

* Corresponding author. Mailing address: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104-6008. Phone: (215) 573-7772. Fax: (215) 573-7023. E-mail: chunter{at}phl.vet.upenn.edu.

Infection and Immunity, December 2000, p. 6932-6938, Vol. 68, No. 12
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Ju, C.-H., Chockalingam, A., Leifer, C. A. (2009). Early Response of Mucosal Epithelial Cells during Toxoplasma gondii Infection. J. Immunol. 183: 7420-7427 [Abstract] [Full Text]  
  • Ibrahim, H. M., Bannai, H., Xuan, X., Nishikawa, Y. (2009). Toxoplasma gondii Cyclophilin 18-Mediated Production of Nitric Oxide Induces Bradyzoite Conversion in a CCR5-Dependent Manner. Infect. Immun. 77: 3686-3695 [Abstract] [Full Text]  
  • Wilson, E. H., Zaph, C., Mohrs, M., Welcher, A., Siu, J., Artis, D., Hunter, C. A. (2006). B7RP-1-ICOS Interactions Are Required for Optimal Infection-Induced Expansion of CD4+ Th1 and Th2 Responses. J. Immunol. 177: 2365-2372 [Abstract] [Full Text]  
  • Tato, C. M., Mason, N., Artis, D., Shapira, S., Caamano, J. C., Bream, J. H., Liou, H.-C., Hunter, C. A. (2006). Opposing roles of NF-{kappa}B family members in the regulation of NK cell proliferation and production of IFN-{gamma}. Int Immunol 18: 505-513 [Abstract] [Full Text]  
  • Combe, C. L., Curiel, T. J., Moretto, M. M., Khan, I. A. (2005). NK Cells Help To Induce CD8+-T-Cell Immunity against Toxoplasma gondii in the Absence of CD4+ T Cells. Infect. Immun. 73: 4913-4921 [Abstract] [Full Text]  
  • Portugal, L. R., Fernandes, L. R., Cesar, G. C., Santiago, H. C., Oliveira, D. R., Silva, N. M., Silva, A. A., Lannes-Vieira, J., Arantes, R. M. E., Gazzinelli, R. T., Alvarez-Leite, J. I. (2004). Infection with Toxoplasma gondii Increases Atherosclerotic Lesion in ApoE-Deficient Mice. Infect. Immun. 72: 3571-3576 [Abstract] [Full Text]  
  • Cusumano, V., Midiri, A., Cusumano, V. V., Bellantoni, A., De Sossi, G., Teti, G., Beninati, C., Mancuso, G. (2004). Interleukin-18 Is an Essential Element in Host Resistance to Experimental Group B Streptococcal Disease in Neonates. Infect. Immun. 72: 295-300 [Abstract] [Full Text]  
  • Gracie, J. A., Robertson, S. E., McInnes, I. B. (2003). Interleukin-18. J. Leukoc. Biol. 73: 213-224 [Abstract] [Full Text]  
  • Wille, U., Villegas, E. N., Craig, L., Peach, R., Hunter, C. A. (2002). Contribution of Interleukin-12 (IL-12) and the CD28/B7 and CD40/CD40 Ligand Pathways to the Development of a Pathological T-Cell Response in IL-10-Deficient Mice. Infect. Immun. 70: 6940-6947 [Abstract] [Full Text]  
  • Kinjo, Y., Kawakami, K., Uezu, K., Yara, S., Miyagi, K., Koguchi, Y., Hoshino, T., Okamoto, M., Kawase, Y., Yokota, K., Yoshino, K., Takeda, K., Akira, S., Saito, A. (2002). Contribution of IL-18 to Th1 Response and Host Defense Against Infection by Mycobacterium tuberculosis: A Comparative Study with IL-12p40. J. Immunol. 169: 323-329 [Abstract] [Full Text]  
  • Scanga, C. A., Aliberti, J., Jankovic, D., Tilloy, F., Bennouna, S., Denkers, E. Y., Medzhitov, R., Sher, A. (2002). Cutting Edge: MyD88 Is Required for Resistance to Toxoplasma gondii Infection and Regulates Parasite-Induced IL-12 Production by Dendritic Cells. J. Immunol. 168: 5997-6001 [Abstract] [Full Text]  
  • Fujigaki, S., Saito, K., Takemura, M., Maekawa, N., Yamada, Y., Wada, H., Seishima, M. (2002). L-Tryptophan-L-Kynurenine Pathway Metabolism Accelerated by Toxoplasmagondii Infection Is Abolished in Gamma Interferon-Gene-Deficient Mice: Cross-Regulation between Inducible Nitric Oxide Synthase and Indoleamine-2,3-Dioxygenase. Infect. Immun. 70: 779-786 [Abstract] [Full Text]  
  • Silva, N. M., Rodrigues, C. V., Santoro, M. M., Reis, L. F. L., Alvarez-Leite, J. I., Gazzinelli, R. T. (2002). Expression of Indoleamine 2,3-Dioxygenase, Tryptophan Degradation, and Kynurenine Formation during In Vivo Infection with Toxoplasma gondii: Induction by Endogenous Gamma Interferon and Requirement of Interferon Regulatory Factor 1. Infect. Immun. 70: 859-868 [Abstract] [Full Text]  
  • Mordue, D. G., Monroy, F., La Regina, M., Dinarello, C. A., Sibley, L. D. (2001). Acute Toxoplasmosis Leads to Lethal Overproduction of Th1 Cytokines. J. Immunol. 167: 4574-4584 [Abstract] [Full Text]  
  • Deng, J. C., Tateda, K., Zeng, X., Standiford, T. J. (2001). Transient Transgenic Expression of Gamma Interferon Promotes Legionella pneumophila Clearance in Immunocompetent Hosts. Infect. Immun. 69: 6382-6390 [Abstract] [Full Text]  
  • Harandi, A. M., Svennerholm, B., Holmgren, J., Eriksson, K. (2001). Interleukin-12 (IL-12) and IL-18 Are Important in Innate Defense against Genital Herpes Simplex Virus Type 2 Infection in Mice but Are Not Required for the Development of Acquired Gamma Interferon-Mediated Protective Immunity. J. Virol. 75: 6705-6709 [Abstract] [Full Text]  
  • Yap, G. S., Ortmann, R., Shevach, E., Sher, A. (2001). A Heritable Defect in IL-12 Signaling in B10.Q/J Mice. II. Effect on Acute Resistance to Toxoplasma gondii and Rescue by IL-18 Treatment. J. Immunol. 166: 5720-5725 [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»