title: Leishmania donovani induces interferon regulatory factor in murine macrophages: a host defense response.
abstract: Macrophages play a key role in directing the host immune response to infection. Interaction of Leishmania donovani with macrophages results in the antagonization of host defense mechanisms by interfering with a cascade of cell signaling processes in the macrophages. Macrophages secrete interferon (IFN), as well as other cytokines, following lipopolysaccharide (LPS) stimulation. The interferon regulatory factors (IRFs) comprise a family of DNA-binding proteins that have been implicated in the transcriptional regulation of IFN and certain IFN-inducible genes. IRF-1 is a transcription factor, which regulates induction of several macrophage effectors and is known to bind to IRF-E site in the inducible nitric oxide synthase (iNOS) promoter. We for the first time report that L. donovani and its surface molecule lipophosphoglycan (LPG) result in a dose- and time-dependent activation of IRF-DNA-binding activity in macrophages. The components of this novel LPG-stimulated IRF-like complex are unclear. The interaction of parasite with the macrophages and not the cellular uptake was important for IRF activation. The use of inhibitors selective for ERK (PD98059) and p38 (SB203580) mitogen-activated protein (MAP) kinase pathway showed that preincubation of cells with either SB203580 or PD98059 did not affect the binding activity of IRF-E, suggesting that both p38 and ERK MAP kinase activation are not necessary for IRF-E activation. It is likely that induction of IRF in response to infection by L. donovani represents a host defense mechanism.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Sridevi
authors.initials: S
authors.lastname: Balaraman
authors.forename: Poonam
authors.initials: P
authors.lastname: Tewary
authors.forename: Vandana Km
authors.initials: VK
authors.lastname: Singh
authors.forename: Rentala
authors.initials: R
authors.lastname: Madhubala
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006028:Glycosphingolipids / Q000494:pharmacology*; D006790:Host-Parasite Interactions / Q000187:drug effects / Q000276:immunology; D050856:Interferon Regulatory Factor-1; D007893:Leishmania donovani / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology*; D051379:Mice; D010750:Phosphoproteins / Q000276:immunology* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D006028:Glycosphingolipids; D050856:Interferon Regulatory Factor-1; C494258:Irf1 protein, mouse; D010750:Phosphoproteins; C008290:lipophosphonoglycan