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Infect Immun, August 1998, p. 3818-3824, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Differential Regulation of the Interleukin-12 Receptor during the Innate Immune Response to Leishmania major

Douglas Jones,1 M. Merle Elloso,1 Louise Showe,2 Donna Williams,2 Giorgio Trinchieri,2 and Phillip Scott1 *

Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania,1 and The Wistar Institute,2 Philadelphia, Pennsylvania 19104

Received 27 February 1998/Returned for modification 14 April 1998/Accepted 26 May 1998

Previous studies have shown the central role of interleukin 12 (IL-12) in the development of resistance to Leishmania major infection in C3H mice. We now show that during the innate immune response the lymph node cells of L. major-infected C3H mice upregulate the IL-12 receptor on CD4+, CD8+, and B220+ cells. An increase in the ability of the lymph node cells to bind IL-12 correlates with 9.3- and 4.6-fold increases in the mRNA expression levels of the IL-12Rbeta 1 and -beta 2 subunits, respectively. In contrast, BALB/c mice, which are susceptible to L. major infection, have no increase in the ability of the lymph node cells to bind IL-12 and correspondingly smaller increases in the mRNA expression levels of the IL-12Rbeta 1 and -beta 2 subunits of 2- and 1.5-fold, respectively. Neutralizing IL-4 and the administration of exogenous IL-12 upregulate IL-12R expression in BALB/c mice, while the neutralization of IL-12 in C3H mice blocks increased IL-12 receptor expression. These experiments reveal an important role for the regulation of the IL-12 receptor during the innate immune response after infection of mice with a pathogen.

* Corresponding author. Mailing address: Department of Pathobiology, University of Pennsylvania, 3800 Spruce St., Philadelphia, PA 19104. Phone: (215) 898-1602. Fax: (215) 573-7023. E-mail: pscott{at}vet.upenn.edu.

Infect Immun, August 1998, p. 3818-3824, Vol. 66, No. 8
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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