title: 5-Lipoxygenase negatively regulates Th1 response during Brucella abortus infection in mice.
abstract: Brucella abortus is a Gram-negative bacterium that infects humans and cattle, causing a chronic inflammatory disease known as brucellosis. A Th1-mediated immune response plays a critical role in host control of this pathogen. Recent findings indicate contrasting roles for lipid mediators in host responses against infections. 5-Lipoxygenase (5-LO) is an enzyme required for the production of the lipid mediators leukotrienes and lipoxins. To determine the involvement of 5-LO in host responses to B. abortus infection, we intraperitoneally infected wild-type and 5-LO-deficient mice and evaluated the progression of infection and concomitant expression of immune mediators. Here, we demonstrate that B. abortus induced the upregulation of 5-LO mRNA in wild-type mice. Moreover, this pathogen upregulated the production of the lipid mediators leukotriene B4 and lipoxin A4 in a 5-LO-dependent manner. 5-LO-deficient mice displayed lower bacterial burdens in the spleen and liver and less severe liver pathology, demonstrating an enhanced resistance to infection. Host resistance paralleled an increased expression of the proinflammatory mediators interleukin-12 (IL-12), gamma interferon (IFN-γ), and inducible nitric oxide synthase (iNOS) during the course of infection. Moreover, we demonstrated that 5-LO downregulated the expression of IL-12 in macrophages during B. abortus infection. Our results suggest that 5-LO has a major involvement in B. abortus infection, by functioning as a negative regulator of the protective Th1 immune responses against this pathogen.
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Júlia Silveira
authors.initials: JS
authors.lastname: Fahel
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Mariana Bueno
authors.initials: MB
authors.lastname: de Souza
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Marco Túlio Ribeiro
authors.initials: MT
authors.lastname: Gomes
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Corsetti
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Natalia B
authors.initials: NB
authors.lastname: Carvalho
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Fabio A V
authors.initials: FA
authors.lastname: Marinho
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Leonardo A
authors.initials: LA
authors.lastname: de Almeida
authors.affiliation: Departamento de Patologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Caliari
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Fabiana Simão
authors.initials: FS
authors.lastname: Machado
authors.affiliation: Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil scozeus@icb.ufmg.br.
authors.forename: Sergio Costa
authors.initials: SC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D058491:Bacterial Load; D002003:Brucella abortus / Q000276:immunology*; D002006:Brucellosis / Q000201:enzymology* / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D018450:Disease Progression; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D007975:Leukotriene B4 / Q000096:biosynthesis; D044045:Lipoxins / Q000096:biosynthesis; D008099:Liver / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology
chemical_list: D044045:Lipoxins; C040527:lipoxin A4; D018664:Interleukin-12; D007975:Leukotriene B4; D007371:Interferon-gamma; D001094:Arachidonate 5-Lipoxygenase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse