title: Lysophosphatidylcholine exacerbates Leishmania major-dendritic cell infection through interleukin-10 and a burst in arginase1 and indoleamine 2,3-dioxygenase activities.
abstract: Leishmania major is an obligate intracellular parasite hosted by phagocytes, including dendritic cells (DCs). Lysophosphatidylcholine (LPC) a pro-oxidant by-product of phospholipase A2 activity can modulate the maturation and function of DCs. However, little is known about its role in L. major infection. This study examined the effects of LPC and lipopolysaccharide (LPS) in BALB/c mouse-derived DC infection by L. major promastigotes, in vitro. Our results showed early divergent effects of LPS and LPC, which lasted up to 24h. In contrast to LPS, LPC worsened DC infection by reversing the immune balance IL-10 vs. TNF-α and IL-6, and inducing a sharp down regulation of CD40 and iNOsynthase activity. In addition, LPC potentiated xanthine oxidase stress, the production of kynurenine by indoleamine 2,3 dioxygenase (IDO), and arginase1 activity in the expense of iNOsynthase. Taken together, our results highlight some biochemical events bypassing the protective Th1 response. They suggest that LPC could facilitate the proliferation of this obligate intracellular parasite by neutralizing oxidative and nitrosative stresses and sustaining both IDO and arginase1 activities.
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene, USTHB, Alger, Algeria.
authors.forename: Nabila
authors.initials: N
authors.lastname: Tounsi
authors.affiliation: Laboratoire d'Immunobiologie, Département de Biologie Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Soraya
authors.initials: S
authors.lastname: Meghari
authors.affiliation: Laboratoire d'Immunobiologie, Département de Biologie Moléculaire, Université Libre de Bruxelles, Gosselies, Belgium.
authors.forename: Muriel
authors.initials: M
authors.lastname: Moser
authors.affiliation: Laboratoire de Biologie Cellulaire et Moléculaire, Faculté des Sciences Biologiques, Université des Sciences et de la Technologie Houari Boumediene, USTHB, Alger, Algeria. Electronic address: djerdjouri_dz@yahoo.fr.
authors.forename: Bahia
authors.initials: B
authors.lastname: Djerdjouri
mesh_terms: D000818:Animals; D001119:Arginase / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D018450:Disease Progression; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008070:Lipopolysaccharides / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D018384:Oxidative Stress; D058408:Th1-Th2 Balance
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D008070:Lipopolysaccharides; D008244:Lysophosphatidylcholines; D016753:Interleukin-10; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C544448:Arg1 protein, mouse; D001119:Arginase
keywords: Arginase1; Bone marrow dendritic cells; Indoleamine 2,3-dioxygenase; Leishmania major; Xanthine oxidase; l-(1)-Stearoyl-lysophosphatidylcholine