Immunomodulatory effects of Amblyomma variegatum saliva on bovine cells: Characterization of cellular responses and identification of molecular determinants

The tropical bont tick, Amblyomma variegatum, is a tick species of veterinary importance and is considered as one of major pest of ruminants in Africa and in the Caribbean. It causes direct skin lesions, transmits heartwater, and reactivates bovine dermatophilosis. Tick saliva is reported to affect overall host responses through immunomodulatory and anti-inflammatory molecules, among other bioactive molecules. The general objective of this study was to better understand the role of saliva in interaction between the Amblyomma tick and the host using cellular biology approaches and proteomics, and to discuss its impact on disease transmission and/or activation. We first focused on the immuno-modulating effects of semi-fed A. variegatum female saliva on bovine peripheral blood mononuclear cells (PBMC) and monocyte-derived macrophages in vitro. We analyzed its immuno-suppressive properties by measuring the effect of saliva on PBMC proliferation, and observed a significant decrease in ConA-stimulated PBMC lymphoproliferation. We then studied the effect of saliva on bovine macrophages using flow cytometry to analyze the expression of MHC-II and co-stimulation molecules (CD40, CD80, and CD86) and by measuring the production of nitric oxide (NO) and pro- or anti-inflammatory cytokines. We observed a significant decrease in the expression of MHC-II, CD40, and CD80 molecules, associated with decreased levels of IL-12-p40 and TNF-α and increased level of IL-10, which could explain the saliva-induced modulation of NO. To elucidate these immunomodulatory effects, crude saliva proteins were analyzed using proteomics with an Orbitrap Elite mass spectrometer. Among the 336 proteins identified in A. variegatum saliva, we evidenced bioactive molecules exhibiting anti-inflammatory, immuno-modulatory, and anti-oxidant properties (e.g., serpins, phospholipases A2, heme lipoprotein). We also characterized an intriguing ubiquitination complex that could be involved in saliva-induced immune modulation of the host. We propose a model for the interaction between A. variegatum saliva and host immune cells that could have an effect during tick feeding by favoring pathogen dissemination or activation by reducing the efficiency of host immune response to the corresponding tick-borne diseases. (Résumé d'auteur

Fire Paradox Fuel Manager: A fuel manager for wildland fire modelling. Diaporama

National audienc

SNAP23-Kif5 complex controls mGlu1 receptor trafficking

International audienc

Le Fuel Manager : un logiciel de représentation et de gestion du combustible

National audienceLa gestion des feux nécessite de considérer la végétation comme un combustible potentiel. Les gestionnaires des espaces naturels doivent évaluer les conséquences des opérations sylvicoles et de gestion du combustible sur le risque feu de forêt. L’INRA d’Avignon a développé une plate-forme européenne pour la modélisation du combustible et l’évaluation des effets du feu. Ce logiciel fait le lien entre les caractéristiques de la végétation, le comportement du feu et l’impact des feux sur les écosystème

FUEL MANAGER: a vegetation assessment and manipulation software for wildfire modeling

International audienceThe FUEL MANAGER is a CAPSIS module that is devoted to fuel modeling, fuel build-up and fire effect assessment. The CAPSIS platform (http://www.inra.fr/capsis) is a software package designed to host forestry models, either growth and yield or dynamics models. In the FUEL MANAGER, fuel modeling is based on a description of the physical properties of the thin particles (leaves, twigs) involved in fire propagation. Three-dimensional scenes can be built and visualized and different kinds of objects can be added to represent both trees and the undergrowth. Each object contains different data from particles properties (mass to volume ratio, surface to volume ratio of leaves and twigs) to bulk density 3D distributions. Tree description is based on allometric relationships between diameter at breast height and leaves or twig biomasses, tree crown shape models, and horizontal and vertical biomass distributions. The physical properties of the different species are based on empirical models or field data downloaded remotely from an object-oriented database. The 3D scene can also be built from input files with various types of format. The fuel scenes can be exported in a format readable by the fire behavior physically-based model FIRETEC. This model requires fuel data (bulk densities, leaf area and fuel moisture content) spatialized in 3D voxels, at a resolution close to 2m. The FUEL MANAGER also enables to simulate fuel build-up and fuel management. Tree growth models account for the effects of site conditions, stand age and competition between trees, as well as management effects (thinning, pruning). They predict competition-induced mortality and the evolution of tree stem diameter, total height, crown height and width. Fuel treatments can be applied to all or part of the scene to reduce appropriately the local biomass available. Fire effects can be derived from empirical models. Based on a scenario of fire intensity and residence time in the stand, crown scorch, crown kill and damage to bark are computed for each individual tree using a variety of published empirical models. These computed damages are then used to assess the tree mortality probability, based on logistic models. Damages to crown and bole can be visualized in the 3D frame. The FUEL MANAGER is a very promising tool for the investigation of fuel management scenarios. It is based on recent technologies for visualization and scene manipulation and on recent research results for fuel and fire effect modelin

Proteomic Analysis of the Promastigote Secretome of Seven Leishmania Species

International audienceLeishmaniasis is one of the most impactful parasitic diseases worldwide, endangering the lives of 1 billion people every year. There are 20 different species of Leishmania able to infect humans, causing cutaneous (CL), visceral (VL), and/or mucocutaneous leishmaniasis (MCL). Leishmania parasites are known to secrete a plethora of proteins to establish infection and modulate the host's immune system. In this study, we analyzed using tandem mass spectrometry the total protein content of the secretomes produced by promastigote forms from seven Leishmania species grown in serum-free in vitro cultures. The core secretome shared by all seven Leishmania species corresponds to up to one-third of total secreted proteins, suggesting conserved mechanisms of adaptation to the vertebrate host. The relative abundance confirms the importance of known virulence factors and some proteins uniquely present in CL- or VL-causing species and may provide further insight regarding their pathogenesis. Bioinformatic analysis showed that most proteins were secreted via unconventional mechanisms, with an important role for vesicle-based secretion for all species. Gene Ontology annotation and enrichment analyses showed a high level of functional conservation among species. This study contributes to the current knowledge on the biological significance of differently secreted proteins and provides new information on the correlation of Leishmania secretome to clinical outcomes and species-specific pathogenesis