title: Interferon-gamma and nitric oxide in combination with antibodies are key protective host immune factors during trypanosoma congolense Tc13 Infections.
abstract: The control of chronic Trypanosoma congolense trypanosomiasis was analyzed using several gene-deficient mouse strains. First, interferon (IFN)-gamma receptor (IFN-gamma-R)-deficient mice were used to show that IFN- gamma -mediated immune activation is crucial for parasitemia control. Second, infections in major histocompatibility complex (MHC) class II-deficient mice indicate that this molecule is needed for initiation of IFN- gamma and subsequent tumor necrosis factor (TNF) production. Downstream of IFN-gamma-R signaling, inducible NO synthase (iNOS)-dependent trypanosome killing occurs, as is shown by the hypersusceptible phenotype of iNOS-deficient mice. Besides proinflammatory responses, B cells and, more specifically, immunoglobulin (Ig) G antibodies are crucial for parasite killing. Hence, parasitemia control is abolished in B cell-deficient mice, whereas IgM-deficient mice control the infection as efficiently as do wild-type mice. In addition, splenectomized mice that have a normal IgM response but an impaired IgG2a/3 response fail to control T. congolense infection. Collectively, these results suggest that host protective immunity against T. congolense is critically dependent on the combined action of the proinflammatory mediators/effectors IFN- gamma , TNF, and NO and antiparasite IgGs.
authors.affiliation: Laboratory of Cellular and Molecular Immunology, Department of Molecular and Cellular Recognition, Flanders Interuniversity Institute for Biotechnology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Magez
authors.forename: Magdalena
authors.initials: M
authors.lastname: Radwanska
authors.forename: Michael
authors.initials: M
authors.lastname: Drennan
authors.forename: Lizette
authors.initials: L
authors.lastname: Fick
authors.forename: Toya Nath
authors.initials: TN
authors.lastname: Baral
authors.forename: Frank
authors.initials: F
authors.lastname: Brombacher
authors.forename: Patrick
authors.initials: P
authors.lastname: De Baetselier
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000502:physiology*; D018512:Parasitemia / Q000276:immunology; D013156:Splenectomy; D016019:Survival Analysis; D014348:Trypanosoma congolense / Q000276:immunology*; D014353:Trypanosomiasis, African / Q000276:immunology*
chemical_list: D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009569:Nitric Oxide; D007371:Interferon-gamma