title: The Ly49E Receptor Inhibits the Immune Control of AcuteTrypanosoma cruziInfection.
abstract: The protozoan parasiteTrypanosoma cruzicirculates in the blood upon infection and invades various cells. Parasites intensively multiply during the acute phase of infection and persist lifelong at low levels in tissues and blood during the chronic phase. Natural killer (NK) and NKT cells play an important role in the immune control ofT. cruziinfection, mainly by releasing the cytokine IFN-γ that activates the microbicidal action of macrophages and other cells and shapes a protective type 1 immune response. The mechanisms by which immune cells are regulated to produce IFN-γ duringT. cruziinfection are still incompletely understood. Here, we show that urokinase plasminogen activator (uPA) is induced early uponT. cruziinfection and remains elevated until day 20 post-infection. We previously demonstrated that the inhibitory receptor Ly49E, which is expressed, among others, on NK and NKT cells, is triggered by uPA. Therefore, we compared wild type (WT) to Ly49E knockout (KO) mice for their control of experimentalT. cruziinfection. Our results show that young, i.e., 4- and 6-week-old, Ly49E KO mice control the infection better than WT mice, indicated by a lower parasite load and less cachexia. The beneficial effect of Ly49E depletion is more obvious in 4-week-old male than in female mice and weakens in 8-week-old mice. In young mice, the lowerT. cruziparasitemia in Ly49E KO mice is paralleled by higher IFN-γ production compared to their WT controls. Our data indicate that Ly49E receptor expression inhibits the immune control ofT. cruziinfection. This is the first demonstration that the inhibitory Ly49E receptor can interfere with the immune response to a pathogenin vivo.
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Jessica
authors.initials: J
authors.lastname: Filtjens
authors.affiliation: Laboratory of Parasitology, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Coltel
authors.affiliation: Laboratory of Parasitology, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Cencig
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Taveirne
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Van Ammel
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Aline
authors.initials: A
authors.lastname: Van Acker
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Tessa
authors.initials: T
authors.lastname: Kerre
authors.affiliation: Laboratory of Immunobiology, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven - University of Leuven , Leuven , Belgium.
authors.forename: Patrick
authors.initials: P
authors.lastname: Matthys
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Tom
authors.initials: T
authors.lastname: Taghon
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Vandekerckhove
authors.affiliation: Laboratory of Parasitology, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Yves
authors.initials: Y
authors.lastname: Carlier
authors.affiliation: Laboratory of Parasitology, Faculty of Medicine, Université Libre de Bruxelles , Brussels , Belgium.
authors.forename: Carine
authors.initials: C
authors.lastname: Truyens
authors.affiliation: Laboratory of Experimental Immunology, Ghent University , Ghent , Belgium.
authors.forename: Georges
authors.initials: G
authors.lastname: Leclercq
keywords: IFN-γ; Ly49E receptor; Trypanosoma cruzi; immune control; natural killer cells; urokinase plasminogen activator