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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-12R
1 and
-
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-12R
1 and
-
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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