Differential regulation of the interleukin-12 receptor during the innate immune response to Leishmania major.
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-12Rbeta1 and -beta2 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-12Rbeta1 and -beta2 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.
Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
D
D
Jones
M M
MM
Elloso
L
L
Showe
D
D
Williams
G
G
Trinchieri
P
P
Scott
D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate / Q000276:immunology*; D018664:Interleukin-12 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D018123:Receptors, Interleukin / Q000096:biosynthesis*; D053707:Receptors, Interleukin-12
C508443:Il12rb2 protein, mouse; D018123:Receptors, Interleukin; D053707:Receptors, Interleukin-12; D018664:Interleukin-12; D015847:Interleukin-4