title: Arabinosylated lipoarabinomannan-mediated protection in visceral leishmaniasis through up-regulation of toll-like receptor 2 signaling: an immunoprophylactic approach.
abstract: Visceral leishmaniasis is characterized by severe immunosuppression of the host cell, resulting in loss of the proinflammatory response. Toll-like receptor 2 (TLR2) is involved in myriad disease forms, including visceral leishmaniasis. During Leishmania donovani infection, the parasite modulates TLR2 to suppress interleukin 12 production, indicating the possible involvement of TLR2 in regulation of the immune response against L. donovani infection. Arabinosylated lipoarabinomannan (Ara-LAM) possesses immunomodulatory properties and induces proinflammatory responses via induction of TLR2-mediated signaling. Here, we found that pretreatment of L. donovani-infected macrophages with Ara-LAM caused a significant increase in TLR2 expression along with the activation of TLR2-mediated downstream signaling, facilitating active nuclear translocation of nuclear factor kappaB. These events culminated in up-regulation of the proinflammatory response, which was abrogated by treatment with TLR2-specific small interfering RNA. In vivo experiments were also suggestive of Ara-LAM playing a long-term protective role. This study demonstrates that Ara-LAM confers protection against leishmanial pathogenesis via TLR2 signaling-mediated induction of the proinflammatory response.
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata -700054, India.
authors.forename: Parna
authors.initials: P
authors.lastname: Bhattacharya
authors.forename: Surajit
authors.initials: S
authors.lastname: Bhattacharjee
authors.forename: Gaurav
authors.initials: G
authors.lastname: Gupta
authors.forename: Saikat
authors.initials: S
authors.lastname: Majumder
authors.forename: Anupam
authors.initials: A
authors.lastname: Adhikari
authors.forename: Asok
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Suchandra Bhattacharyya
authors.initials: SB
authors.lastname: Majumdar
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Saha
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007155:Immunologic Factors / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000276:immunology* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000469:parasitology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D007155:Immunologic Factors; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C050016:lipoarabinomannan