Transcriptional inhibition of interleukin-12 promoter activity in Leishmania spp.-infected macrophages.
To establish and persist within a host, Leishmania spp. parasites delay the onset of cell-mediated immunity by suppressing interleukin-12 (IL-12) production from host macrophages. Although it is established that Leishmania spp.-infected macrophages have impaired IL-12 production, the mechanisms that account for this suppression remain to be completely elucidated. Using a luciferase reporter assay assessing IL-12 transcription, we report here that Leishmania major, Leishmania donovani, and Leishmania chagasi inhibit IL-12 transcription in response to interferon-gamma, lipopolysaccharide, and CD40 ligand and that Leishmania spp. lipophosphoglycan, phosphoglycans, and major surface protein are not necessary for inhibition. In addition, all the Leishmania spp. strains and life-cycle stages tested inhibited IL-12 promoter activity. Our data further reveal that autocrine-acting host factors play no role in the inhibitory response and that phagocytosis signaling is necessary for inhibition of IL-12.
Jayakumar
Asha
A
215 Galvin Life Sciences, Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556, USA.
Widenmaier
Robyn
R
Ma
Xiaojing
X
McDowell
Mary Ann
MA
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002460:Cell Line; D006801:Humans; D007111:Immunity, Cellular; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000276:immunology; D007891:Leishmania / Q000276:immunology / Q000502:physiology*; D007896:Leishmaniasis / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010587:Phagocytosis / Q000276:immunology; D011401:Promoter Regions, Genetic / Q000276:immunology / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000276:immunology / Q000502:physiology*
D018664:Interleukin-12