5-Lipoxygenase negatively regulates Th1 response during Brucella abortus infection in mice

• Published in: Infection and immunity Vol. 83; no. 3; pp. 1210 - 1216
• Main Authors: Fahel, Júlia Silveira, de Souza, Mariana Bueno, Gomes, Marco Túlio Ribeiro, Corsetti, Patricia P, Carvalho, Natalia B, Marinho, Fabio A V, de Almeida, Leonardo A, Caliari, Marcelo V, Machado, Fabiana Simão, Oliveira, Sergio Costa
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.03.2015
• Subjects: Animals; Arachidonate 5-Lipoxygenase - deficiency; Arachidonate 5-Lipoxygenase - genetics; Arachidonate 5-Lipoxygenase - immunology; Bacterial Load; Brucella abortus; Brucella abortus - immunology; Brucellosis - enzymology; Brucellosis - immunology; Brucellosis - microbiology; Brucellosis - pathology; Disease Progression; Gene Expression Regulation; Host Response and Inflammation; Host-Pathogen Interactions; Immunity, Innate; Injections, Intraperitoneal; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin-12 - genetics; Interleukin-12 - immunology; Leukotriene B4 - biosynthesis; Lipoxins - biosynthesis; Liver - immunology; Liver - microbiology; Liver - pathology; Macrophages - immunology; Macrophages - microbiology; Macrophages - pathology; Mice; Mice, Knockout; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - immunology; Spleen - immunology; Spleen - microbiology; Spleen - pathology; Th1 Cells - immunology; Th1 Cells - microbiology; Th1 Cells - pathology
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/iai.02592-14

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.