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.
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February 2008
Research Article|
February 01 2008
Transcriptional Inhibition of Interleukin-12 Promoter Activity in Leishmania Spp.–Infected Macrophages
Asha Jayakumar;
Asha Jayakumar
215 Galvin Life Sciences, Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556. mcdowell.11@nd.edu
* These authors contributed equally to the manuscript
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Robyn Widenmaier;
Robyn Widenmaier
215 Galvin Life Sciences, Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556. mcdowell.11@nd.edu
* These authors contributed equally to the manuscript
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Xiaojing Ma;
Xiaojing Ma
215 Galvin Life Sciences, Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556. mcdowell.11@nd.edu
† Department of Microbiology and Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021
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Mary Ann McDowell
Mary Ann McDowell
215 Galvin Life Sciences, Center for Global Health and Infectious Diseases, Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana 46556. mcdowell.11@nd.edu
‡ To whom correspondence should be addressed
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J Parasitol (2008) 94 (1): 84–93.
Citation
Asha Jayakumar, Robyn Widenmaier, Xiaojing Ma, Mary Ann McDowell; Transcriptional Inhibition of Interleukin-12 Promoter Activity in Leishmania Spp.–Infected Macrophages. J Parasitol 1 February 2008; 94 (1): 84–93. doi: https://doi.org/10.1645/GE-1153.1
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