1. Protective Role of 5-Lipoxigenase during Leishmania infantum Infection Is Associated with Th17 Subset
- Author
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Laís A. Sacramento, João Santana da Silva, Roque Pacheco de Almeida, Vanessa Carregaro, and Fernando Q. Cunha
- Subjects
Male ,Article Subject ,INFECÇÕES POR PROTOZOÁRIOS ,lcsh:Medicine ,Protective Agents ,General Biochemistry, Genetics and Molecular Biology ,Host-Parasite Interactions ,Proinflammatory cytokine ,Mice ,Immune system ,Cell Movement ,parasitic diseases ,medicine ,Animals ,Humans ,Parasites ,Leishmania infantum ,Arachidonate 5-Lipoxygenase ,General Immunology and Microbiology ,biology ,lcsh:R ,Leishmaniasis ,Dendritic Cells ,General Medicine ,Lipid signaling ,Th1 Cells ,biology.organism_classification ,medicine.disease ,In vitro ,Enzyme Activation ,Visceral leishmaniasis ,Neutrophil Infiltration ,Arachidonate 5-lipoxygenase ,Immunology ,biology.protein ,Cytokines ,Leishmaniasis, Visceral ,Th17 Cells ,Female ,Research Article - Abstract
Visceral leishmaniasis (VL) is a chronic and fatal disease caused byLeishmania infantumin Brazil. Leukocyte recruitment to infected tissue is a crucial event for the control of infections such as VL. Leucotriens are lipid mediators synthesized by 5-lipoxygenase (5-LO) and they display a protective role against protozoan parasites by inducing several functions in leucocytes. We determined the role of 5-LO activity in parasite control, focusing on the inflammatory immune response againstLeishmania infantuminfection. LTB4is released duringin vitroinfection. The genetic ablation of 5-LO promoted susceptibility in highly resistant mice strains, harboring more parasites into target organs. The susceptibility was related to the failure of neutrophil migration to the infectious foci. Investigating the neutrophil failure, there was a reduction of proinflammatory cytokines involved in the related Th17 axis released into the organs. Genetic ablation of 5-LO reduced the CD4+T cells producing IL-17, without interfering in Th1 subset.L. infantumfailed to activate DC from5-LO-/-, showing reduced surface costimulatory molecule expression and proinflammatory cytokines involved in Th17 differentiation. BLT1blockage with selective antagonist interferes with DC maturation and proinflammatory cytokines release. Thus, 5-LO activation coordinates the inflammatory immune response involved in the control of VL.
- Published
- 2014