Protective Role of 5-Lipoxigenase during Leishmania infantum Infection Is Associated with Th17 Subset

Visceral leishmaniasis (VL) is a chronic and fatal disease caused by Leishmania infantum in 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 against Leishmania infantum infection. LTB4 is released during in vitro infection. 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. infantum failed to activate DC from 5-LO−/−, showing reduced surface costimulatory molecule expression and proinflammatory cytokines involved in Th17 differentiation. BLT1 blockage 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.

• Publication year

  2014

• Venue

  BioMed Research International

• Publication date

  2014-09-21

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1155/2014/264270PMID 25309905PMCID 4189762
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Human neutrophils produce IL-12, IL-10, PGE2 and LTB4 in response to Paracoccidioides brasiliensis. Involvement of TLR2, mannose receptor and dectin-1.

  2014cited by this paper
• Leukotriene B4 amplifies eosinophil accumulation in response to nematodes

  2014cited by this paper
• Leukotriene B4 Modulates P2X7 Receptor–Mediated Leishmania amazonensis Elimination in Murine Macrophages

  2014cited by this paper
• Understanding the Mechanisms Controlling Leishmania amazonensis Infection In Vitro: The Role of LTB4 Derived From Human Neutrophils

  2014cited by this paper
• 5-Lipoxygenase Activity Increases Susceptibility to Experimental Paracoccidioides brasiliensis Infection

  2013cited by this paper
• The C-type lectin receptors dectin-1, MR, and SIGNR3 contribute both positively and negatively to the macrophage response to Leishmania infantum.

  2013cited by this paper
• Successful therapy of visceral leishmaniasis with curdlan involves T-helper 17 cytokines.

  2013cited by this paper
• The Pivotal Role of 5-Lipoxygenase-Derived LTB4 in Controlling Pulmonary Paracoccidioidomycosis

  2013cited by this paper
• 5-Lipoxygenase Deficiency Impairs Innate and Adaptive Immune Responses during Fungal Infection

  2012cited by this paper
• Leukotriene B4 amplifies NF-κB activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression.

  2011cited by this paper
• Monocyte Chemoattractant Protein 1 Regulates Pulmonary Host Defense via Neutrophil Recruitment during Escherichia coli Infection

  2011cited by this paper
• Leukocytes Infiltrate the Skin and Draining Lymph Nodes in Response to the Protozoan Leishmania infantum chagasi

  2010cited by this paper
• 5-lipoxygenase is a key determinant of acute myocardial inflammation and mortality during Trypanosoma cruzi infection.

  2010cited by this paper
• Intrapulmonary Administration of Leukotriene B4 Enhances Pulmonary Host Defense against Pneumococcal Pneumonia

  2010cited by this paper
• Functions of T cells in asthma: more than just TH2 cells

  2010cited by this paper
• The leukotriene B4 receptor, BLT1, is required for the induction of experimental autoimmune encephalomyelitis.

  2010cited by this paper
• Structures and mechanisms of enzymes in the leukotriene cascade.

  2010cited by this paper
• Effects of leukotriene B4 and prostaglandin E2 on the differentiation of murine Foxp3+ T regulatory cells and Th17 cells.

  2009cited by this paper
• IL-17 and Th17 Cells.

  2009cited by this paper
• CD11b+ Myeloid Cells Are the Key Mediators of Th2 Cell Homing into the Airway in Allergic Inflammation1

  2009cited by this paper
• Phlebotomine salivas inhibit immune inflammation‐induced neutrophil migration via an autocrine DC‐derived PGE2/IL‐10 sequential pathway

  2008cited by this paper
• Differentiation and function of Th17 T cells.

  2007cited by this paper
• Leukotriene B4-Mediated Release of Antimicrobial Peptides against Cytomegalovirus Is BLT1 Dependent

  2007cited by this paper
• Inhibition of leukotriene biosynthesis abrogates the host control of Mycobacterium tuberculosis.

  2007cited by this paper
• LEUKOTRIENE B4/LEUKOTRIENE B4 RECEPTOR PATHWAY IS INVOLVED IN HEPATIC MICROCIRCULATORY DYSFUNCTION ELICITED BY ENDOTOXIN

  2007cited by this paper
• How human neutrophils kill and degrade microbes: an integrated view

  2007cited by this paper
• Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania.

  2007cited by this paper
• Regulation of dendritic cell migration and adaptive immune response by leukotriene B4 receptors: a role for LTB4 in up-regulation of CCR7 expression and function.

  2007cited by this paper
• CD8+ T lymphocytes and leukotriene B4: novel interactions in the persistence and progression of asthma.

  2006cited by this paper
• Leukotrienes Are Essential for the Control of Leishmania amazonensis Infection and Contribute to Strain Variation in Susceptibility1

  2006cited by this paper
• Chemokine Gene Expression in Toll-Like Receptor-Competent and -Deficient Mice Infected with Leishmania major

  2004cited by this paper
• Release of anti-HIV mediators after administration of leukotriene B4 to humans.

  2004cited by this paper
• Myd88-Dependent In Vivo Maturation of Splenic Dendritic Cells Induced by Leishmania donovani and Other Leishmania Species

  2004cited by this paper
• Differential expression of leukotriene B4 receptor subtypes (BLT1 and BLT2) in human synovial tissues and synovial fluid leukocytes of patients with rheumatoid arthritis.

  2003cited by this paper
• Toll-like receptor-4 (TLR4) signaling augments chemokine-induced neutrophil migration by modulating cell surface expression of chemokine receptors

  2003cited by this paper
• Neutrophil granules and secretory vesicles in inflammation.

  2003cited by this paper
• Genetically Resistant Mice Lacking MyD88-Adapter Protein Display a High Susceptibility to Leishmania major Infection Associated with a Polarized Th2 Response1

  2003cited by this paper
• Toll-Like Receptors in Health and Disease: Complex Questions Remain1

  2003cited by this paper
• Interleukin-23 Promotes a Distinct CD4 T Cell Activation State Characterized by the Production of Interleukin-17*

  2003cited by this paper
• Dendritic cells produce eicosanoids, which modulate generation and functions of antigen-presenting cells.

  2002cited by this paper
• Defensin-rich granules of human neutrophils: characterization of secretory properties.

  2002cited by this paper
• Divergent expression of inflammatory dermal chemokines in cutaneous leishmaniasis *

  2002cited by this paper
• Leukotriene B4 Augments Neutrophil Phagocytosis of Klebsiella pneumoniae

  2001cited by this paper
• Intracellular compartmentalization of leukotriene synthesis: unexpected nuclear secrets

  2001cited by this paper
• Organ-specific immune responses associated with infectious disease.

  2000cited by this paper
• 5-lipoxygenase expression in dendritic cells generated from CD34(+) hematopoietic progenitors and in lymphoid organs.

  2000cited by this paper
• Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways.

  1999cited by this paper
• Dendritic cells, but not macrophages, produce IL‐12 immediately following Leishmania donovani infection

  1998cited by this paper
• 5-Lipoxygenase expression in Langerhans cells of normal human epidermis.

  1998cited by this paper
• Uptake of Leishmania major Amastigotes Results in Activation and Interleukin 12 Release from Murine Skin–derived Dendritic Cells: Implications for the Initiation of Anti-Leishmania Immunity

  1998cited by this paper
• The regulation of CD11b integrin levels on human blood leukocytes and leukotriene B4-stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111).

  1997cited by this paper
• T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines

  1996cited by this paper
• Late phase response during nasal challenge: effect of astemizole on leukotriene B4 levels.

  1996cited by this paper
• Toxoplasma gondii alters eicosanoid release by human mononuclear phagocytes: role of leukotrienes in interferon gamma-induced antitoxoplasma activity

  1994cited by this paper
• Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice

  1992cited by this paper
• Leukocyte inhibitory factor activates human neutrophils and macrophages to release leukotriene B4 and thromboxanes.

  1990cited by this paper
• Site-restricted persistent cytomegalovirus infection after selective long-term depletion of CD4+ T lymphocytes

  1989cited by this paper
• Mechanism of action of glucocorticosteroids. Inhibition of T cell proliferation and interleukin 2 production by hydrocortisone is reversed by leukotriene B4.

  1986cited by this paper
• On the nature of the 5-lipoxygenase reaction in human leukocytes: characterization of a membrane-associated stimulatory factor.

  1985cited by this paper
• Arachidonic acid metabolism by murine peritoneal macrophages infected with Leishmania donovani: in vitro evidence for parasite-induced alterations in cyclooxygenase and lipoxygenase pathways.

  1985cited by this paper
• Superoxide production of human polymorphonuclear leukocytes stimulated by leukotriene B4.

  1984cited by this paper
• Arachidonic acid metabolism in murine leishmaniasis (Donovani): ex-vivo evidence for increased cyclooxygenase and 5-lipoxygenase activity in spleen cells.

  1984cited by this paper
• Leukotrienes: mediators of immediate hypersensitivity reactions and inflammation.

  1983cited by this paper
• The stimulation of lysosomal enzyme secretion from human polymorphonuclear leucocytes by leukotriene B4

  1981influential reference
• Selective feed-back inhibition of the 5-lipoxygenation of arachidonic acid in human T-lymphocytes.

  1981cited by this paper
• Lipoxygenation of arachidonic acid as a source of polymorphonuclear leukocyte chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis.

  1980cited by this paper
• Leukotriene B: a potential mediator of inflammation

  1980cited by this paper
• Leukotriene B, a potent chemokinetic and aggregating substance released from polymorphonuclear leukocytes

  1980cited by this paper

• Evaluation of the Cutaneous Immunological Milieu Before and After Treatment With Meglumine Antimoniate in Dogs Naturally Affected by Leishmaniosis due to Leishmania infantum.

  2026cites this paper
• Evolving immunometabolic response to the early Leishmania infantum infection in the spleen of BALB/c mice described by gene expression profiling.

  2023cites this paper
• Fatty Acid Composition and Metabolism in Leishmania Parasite Species: Potential Biomarkers or Drug Targets for Leishmaniasis?

  2023cites this paper
• Toxoplasma gondii Infection Decreases Intestinal 5-Lipoxygenase Expression, while Exogenous LTB4 Controls Parasite Growth

  2022cites this paper
• The Role of Surface Molecules in Host Responses of Leishmaniasis: Focus on Lipid Mediators

  2022cites this paper
• Emerging Role of Dendritic Cell Intervention in the Treatment of Inflammatory Bowel Disease

  2022cites this paper
• T Lymphocyte Exhaustion During Human and Experimental Visceral Leishmaniasis

  2022cites this paper
• Immunization With a DNA Vaccine Encoding the Toxoplasma gondii’ s GRA39 Prolongs Survival and Reduce Brain Cyst Formation in a Murine Model

  2021cites this paper
• Neutrophils and Visceral Leishmaniasis: Impact on innate immune response and cross‐talks with macrophages and dendritic cells

  2020cites this paper
• Papel da enzima 5-lipoxigenase na infecção oral por Toxoplasma gondii

  2018cites this paper
• Lutzomyia longipalpis Saliva Drives Interleukin-17-Induced Neutrophil Recruitment Favoring Leishmania infantum Infection

  2018cites this paper
• Live Attenuated Leishmania donovani Centrin Gene–Deleted Parasites Induce IL-23–Dependent IL-17–Protective Immune Response against Visceral Leishmaniasis in a Murine Model

  2018cites this paper
• Purinergic Cooperation Between P2Y2 and P2X7 Receptors Promote Cutaneous Leishmaniasis Control: Involvement of Pannexin-1 and Leukotrienes

  2018cites this paper
• Inflammatory and Pro-resolving Lipids in Trypanosomatid Infections: A Key to Understanding Parasite Control

  2018cites this paper
• Leishmania infantum Parasites Subvert the Host Inflammatory Response through the Adenosine A2A Receptor to Promote the Establishment of Infection

  2017cites this paper
• The recent colonization of south Brazil by the Azores chromis Chromis limbata.

  2017cites this paper
• Diametric Role of the Latency-Associated Protein Acr1 of Mycobacterium tuberculosis in Modulating the Functionality of Pre- and Post-maturational Stages of Dendritic Cells

  2017cites this paper
• The Contribution of Immune Evasive Mechanisms to Parasite Persistence in Visceral Leishmaniasis

  2016cites this paper
• Crosstalk between purinergic receptors and lipid mediators in leishmaniasis

  2016cites this paper
• Caracterização da sinalização via IL-1R durante a infecção experimental por Leishmania infantum

  2016cites this paper
• Nucleosides Present on Phlebotomine Saliva Induce Immunossuppression and Promote the Infection Establishment

  2015cites this paper
• Toll-Like Receptor 9 Signaling in Dendritic Cells Regulates Neutrophil Recruitment to Inflammatory Foci following Leishmania infantum Infection

  2015cites this paper