Transcriptional inhibition of interleukin-12 promoter activity in Leishmania spp.-infected macrophages.

TitleTranscriptional inhibition of interleukin-12 promoter activity in Leishmania spp.-infected macrophages.
Publication TypeJournal Article
Year of Publication2008
AuthorsJayakumar A, Widenmaier R, Ma X, McDowell MAnn
JournalJ Parasitol
Date Published2008 Feb
KeywordsAnimals, Autocrine Communication, Cell Line, Humans, Immunity, Cellular, Interleukin-12, Leishmania, Leishmaniasis, Macrophages, Mice, Mice, Inbred BALB C, Phagocytosis, Promoter Regions, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Transcription, Genetic

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.

Alternate JournalJ Parasitol
PubMed ID18372625
PubMed Central IDPMC2665708
Grant ListR01 AI056242 / AI / NIAID NIH HHS / United States
R01 AI056242-04 / AI / NIAID NIH HHS / United States

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