Journal Article

Ir-LBP, an Ixodes ricinus Tick Salivary LTB4-Binding Lipocalin, Interferes with Host Neutrophil Function

Fievez, Laurence, Bureau, Fabrice, Brossard, Michel, Vanhamme, Luc, Vanhaeverbeek, Michel, Adam, Benoît, Santini, Sébastien, Grosjean, Amélie, Beaufays, Jérôme, Godfroid, Edmond, Lins, Laurence, Menten-Dedoyart, Catherine, Prévôt, Pierre-Paul, Decrem, Yves, Brasseur, Robert, Heinen, Ernst

2008

Overview

During their blood meal, ticks secrete a wide variety of proteins that can interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. We previously identified 14 new lipocalin genes in the tick Ixodes ricinus. One of them codes for a protein that specifically binds leukotriene B4 with a very high affinity (Kd: +/-1 nM), similar to that of the neutrophil transmembrane receptor BLT1. By in silico approaches, we modeled the 3D structure of the protein and the binding of LTB4 into the ligand pocket. This protein, called Ir-LBP, inhibits neutrophil chemotaxis in vitro and delays LTB4-induced apoptosis. Ir-LBP also inhibits the host inflammatory response in vivo by decreasing the number and activation of neutrophils located at the tick bite site. Thus, Ir-LBP participates in the tick's ability to interfere with proper neutrophil function in inflammation. These elements suggest that Ir-LBP is a \"scavenger\" of LTB4, which, in combination with other factors, such as histamine-binding proteins or proteins inhibiting the classical or alternative complement pathways, permits the tick to properly manage its blood meal. Moreover, with regard to its properties, Ir-LBP could possibly be used as a therapeutic tool for illnesses associated with an increased LTB4 production.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acids / Amino Acid Sequence / Analysis / Animals / Animals, Genetically Modified / Apoptosis / Binding / Biochemistry, biophysics & molecular biology / Biochemistry, Molecular Biology / Biochimie, biophysique & biologie moléculaire / Bites (Injuries) / Blood / Cell activation / Chemotaxis / Computer Simulation / Crystallography / Female / Fines & penalties / Granulocytes / Histamine / Histology / Host-Parasite Interactions - genetics / Host-Parasite Interactions - immunology / Host-Parasite Interactions/genetics/immunology / Illnesses / Immunology / Immunology/Immune Response / Immunology/Leukocyte Activation / Inflammation / Inflammatory response / Insect bites / Iridium / Ixodes - immunology / Ixodes - metabolism / Ixodes ricinus / Ixodes/immunology/metabolism / Ixodidae / Laboratories / Leukocytes (neutrophilic) / Leukotriene B4 / Leukotriene B4 - metabolism / Life Sciences / Ligands / Lipocalin / Lipocalins - genetics / Lipocalins - metabolism / Lipocalins - physiology / Lipocalins/genetics/metabolism/physiology / Models, Molecular / Molecular biology / Molecular Biology/Bioinformatics / Molecular Sequence Data / Morphology / Neutrophil Activation - physiology / Neutrophils / Neutrophils - physiology / Physiology / Protein Binding / Protein structure / Proteins / Rabbits / Receptors, Leukotriene B4 - chemistry / Receptors, Leukotriene B4 - genetics / Receptors, Leukotriene B4 - metabolism / Receptors, Leukotriene B4 - physiology / Receptors, Leukotriene B4/chemistry/genetics/metabolism/physiology / Salivary Proteins and Peptides - genetics / Salivary Proteins and Peptides - metabolism / Salivary Proteins and Peptides - physiology / Salivary Proteins and Peptides/genetics/metabolism/physiology / Sciences du vivant / Sequence Homology, Amino Acid / Structural Biology / Three dimensional models / Tick Infestations - immunology / Ticks