title: Toll-like receptors and CD40 modulate each other's expression affecting Leishmania major infection.
abstract: Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite Leishmania major. While polyinosinic-polycytidylic acid [poly (I:C)], a TLR-3 ligand, lipopolysaccharide (LPS), a TLR-4 ligand, imiquimod, a TLR-7/8 ligand and cytosine-phosphate-guanosine (CpG), a TLR-9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR-9 expression. Therefore, we tested the synergism between CD40 and CpG in anti-leishmanial immune response. In Leishmania-infected macrophages, CpG was found to reduce CD40-induced extracellular stress-regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)-10, these ligands had differential effects on CD40-induced IL-1α, IL-6 and IL-12 production. CpG significantly enhanced the anti-leishmanial function of CD40 with differential effects on IL-4, IL-10 and interferon (IFN)-γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40-TLR cross-talk that regulated the experimental L. major infection.
authors.affiliation: National Centre for Cell Science, Pune, India.
authors.forename: H S
authors.initials: HS
authors.lastname: Chandel
authors.forename: S P
authors.initials: SP
authors.lastname: Pandey
authors.forename: D
authors.initials: D
authors.lastname: Shukla
authors.forename: K
authors.initials: K
authors.lastname: Lalsare
authors.forename: S K
authors.initials: SK
authors.lastname: Selvaraj
authors.forename: M K
authors.initials: MK
authors.lastname: Jha
authors.forename: B
authors.initials: B
authors.lastname: Saha
mesh_terms: D000634:Aminoquinolines / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D019013:CD40 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects / Q000276:immunology*; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000276:immunology; D000077271:Imiquimod; D018320:Leishmania major / Q000276:immunology* / Q000502:physiology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000276:immunology; D020239:Receptor Cross-Talk / Q000187:drug effects / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000819:agonists; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: D000634:Aminoquinolines; D019013:CD40 Antigens; C526902:CpG ODN 2216; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D000077271:Imiquimod
keywords: CD40; Leishmania; Toll-like receptor; macrophages