Lipness (lipid and lipid transfer in sterile and septic inflammation)

We are studying the role of Lipoproteins and lipid molecules, as well as the impact of lipid exchanges in the modulation of inflammation with applications in chronic inflammation (atherosclerosis) and acute inflammatory diseases including sepsis.

Our research themes :

Main investigators :

  • Laurent Lagrost
  • Valérie Deckert
  • Thomas Gautier
  • Maxime Nguyen

Lipopolysaccharides (LPS) bind and activate Toll like receptor 4 at the surface of immune cells, leading to the release of pro-inflammatory cytokines and to inflammation. Alternatively, bacterial blebs forming large LPS aggregates can be disrupted and molecular transfer of LPS towards lipoproteins can occur. It results in its neutralization and elimination back to the liver, namely the reverse LPS transport pathway (RLT). Recent observations suggest that PLTP and CETP, as members of the lipid transfer/lipopolysaccharide binding protein gene family play a driving role in RLT, thus modulating inflammation and innate immunity.

Recent publications :

  • Deckert V, Lemaire S, Ripoll P-J, de Barros J-PP, Labbé J, Borgne CC-L, Turquois V, Maquart G, Larose D, Desroche N, Ménétrier F, Le Guern N, Lebrun LJ, Desrumaux C, Gautier T, Grober J, Thomas C, Masson D, Houdebine L-M, Lagrost L. Recombinant human plasma phospholipid transfer protein (PLTP) to prevent bacterial growth and to treat sepsis. Sci Rep. 2017;7:3053.
  • Sali W, Patoli D, Pais de Barros J-P, Labbé J, Deckert V, Duhéron V, Le Guern N, Blache D, Chaumont D, Lesniewska E, Gasquet B, Paul C, Moreau M, Denat F, Masson D, Lagrost L, Gautier T. Polysaccharide Chain Length of Lipopolysaccharides From Salmonella Minnesota Is a Determinant of Aggregate Stability, Plasma Residence Time and Proinflammatory Propensity in vivo. Front Microbiol. 2019;10:1774.
  • Nguyen M, Pallot G, Jalil A, Tavernier A, Dusuel A, Le Guern N, Lagrost L, Pais de Barros J-P, Choubley H, Bergas V, Guinot P-G, Masson D, Bouhemad B, Gautier T. Intra-Abdominal Lipopolysaccharide Clearance and Inactivation in Peritonitis: Key Roles for Lipoproteins and the Phospholipid Transfer Protein. Front Immunol. 2021;12:622935.
  • Main investigators :

    • Stéphane Mandard
    • Thomas Gautier

    Some evidence indicates that LPS molecules are removed from the body through biliary excretion as the final step of the reverse LPS transport pathway. While some previous works have documented the biophysical interaction of endotoxins with purified bile acids, its pathophysiological consequence in terms of proinflammatory capacity of LPS is not completely clear. We aim at better understanding the link between bile acid metabolism and neutralization/detoxification of LPS.

    Main investigators :

    • Jean-Pierre Quenot
    • Belaid Bouhemad
    • Laurent Lagrost

    The incidence of severe sepsis and septic shock is about 15% of all admission in ICU and the hospital mortality is 25% and 49%, respectively. Despite significant advances in our understanding of the pathophysiology of severe sepsis and septic shock, attempts to translate these finding into novel treatments and improved outcomes for patients have been disappointing. One main objective of the Lipness team is to determine to which extent LPS neutralization and elimination may constitute a new and relevant approach to improve clinical outcome of septic shock.

    Recent publication :

  • Dargent A, Pais De Barros J-P, Ksiazek E, Fournel I, Dusuel A, Rerole AL, Choubley H, Masson D, Lagrost L, Quenot J-P. Improved quantification of plasma lipopolysaccharide (LPS) burden in sepsis using 3-hydroxy myristate (3HM): a cohort study. Intensive Care Med. 2019;45:1678–1680.
  • Main investigator :

    • Jacques Grober

    In healthy subjects, moderate endotoxemia has been associated with increased insulin sensitivity on the short term whereas insulin resistance can occur at later time points. We have recently shown that LPS is able to increase circulating levels of glucagon-like peptide-1 (GLP-1), an incretin involved in insulin secretion stimulated by glucose (GSIS).

    Recent publication :

  • Lebrun LJ, Lenaerts K, Kiers D, Pais de Barros J-P, Le Guern N, Plesnik J, Thomas C, Bourgeois T, Dejong CHC, Kox M, Hundscheid IHR, Khan NA, Mandard S, Deckert V, Pickkers P, Drucker DJ, Lagrost L, Grober J. Enteroendocrine L Cells Sense LPS after Gut Barrier Injury to Enhance GLP-1 Secretion. Cell Rep. 2017;21:1160–1168.
  • Main investigators :

    • David Masson
    • Charles Thomas

    Phospholipids are continuously remodeled through deacylation and reacylation by the opposite actions of phospholipase A2, and lysophospholipid acyl-transferases (LPLATs). LPLATs affect both the PUFA content of phospholipids and the availability of free fatty acids such as arachidonic acid used for eicosanoid synthesis. By using specific mouse models and samples from human patients, we assess the impact of phospholipid and fatty acid metabolism in myeloid cells on inflammation and atherosclerosis development.

    Recent publications :

  • Ménégaut L, Jalil A, Thomas C, Masson D. Macrophage fatty acid metabolism and atherosclerosis: The rise of PUFAs. Atherosclerosis. 2019;291:52–61.
  • Ménégaut L, Thomas C, Jalil A, Julla JB, Magnani C, Ceroi A, Basmaciyan L, Dumont A, Goff WL, Mathew MJ, Rébé C, Dérangère V, Laubriet A, Crespy V, Barros J-PP de, Steinmetz E, Venteclef N, Saas P, Lagrost L, Masson D. Interplay between Liver X Receptor and Hypoxia Inducible Factor 1α Potentiates Interleukin-1β Production in Human Macrophages. Cell Reports [Internet]. 2020 [cited 2020 May 19];31. Available from: https://www.cell.com/cell-reports/abstract/S2211-1247(20)30618-5
  • Main investigators :

    • Charles Thomas
    • Pierre Emmanuel Charles
    • Mathieu Blot

    Mitophagy is a mitochondria-dedicated autophagy allowing clearance of damaged mitochondria in the cell. Our investigations aim to unravel the signaling pathway resulting to the inhibition of mitophagy by LPS and IFNγ in macrophages. We investigate whether this inhibition of mitophagy occurs in macrophages and polynuclear neutrophils in the context of bacterial infection such as sepsis or experimental models of pneumonia and whether modulation of mitophagy may affect the inflammatory and bactericidal responses.

    Recent publications :

  • Patoli D, Mignotte F, Deckert V, Dusuel A, Dumont A, Rieu A, Jalil A, Van Dongen K, Bourgeois T, Gautier T, Magnani C, Le Guern N, Mandard S, Bastin J, Djouadi F, Schaeffer C, Guillaumot N, Narce M, Nguyen M, Guy J, Dargent A, Quenot J-P, Rialland M, Masson D, Auwerx J, Lagrost L, Thomas C. Inhibition of mitophagy drives macrophage activation and antibacterial defense during sepsis. J Clin Invest. 2020
  • Blot M, Jacquier M, Pauchard L-A, Rebaud C, Marlin C, Hamelle C, Bataille A, Croisier D, Thomas C, Jalil A, Mirfendereski H, Piroth L, Chavanet P, Bensoussan D, Laroye C, Reppel L, Charles P-E. Adverse Mechanical Ventilation and Pneumococcal Pneumonia Induce Immune and Mitochondrial Dysfunctions Mitigated by Mesenchymal Stem Cells in Rabbits. Anesthesiology. 2022;136:293–313.
  • Main investigators :

    • Jérome Bellenger
    • Sandrine Bellenger
    • Michel Narce

    Metabolic syndrome (MS) is tightly associated with low grade inflammation, endotoxemia and intestinal microbiota modulation. A decrease of the n-6/n-3 ratio by n-3 PUFA-enriched diets can exert beneficial effects during obesity and insulin-resistance in rodent models and microbiome changes could improve intestinal integrity and reduce hepatic and systemic inflammation. We recently showed (by microbiome transplantation) that endogenously synthesized n-3 PUFAs exert beneficial effects during MS. We are now focused on 1) evaluating the effects of fatty acids on intestinal barrier 2) deciphering molecular mechanisms involved in the relative contribution of n-3-enriched microbiota in the prevention of MS. A special attention is paid on the mucus layer in terms of strengthening the intestinal barrier integrity by n-3 fatty acids.

    Recent publication :

  • Bidu C, Escoula Q, Bellenger S, Spor A, Galan M, Geissler A, Bouchot A, Dardevet D, Morio B, Cani PD, Lagrost L, Narce M, Bellenger J. The Transplantation of ω3 PUFA-Altered Gut Microbiota of fat-1 Mice to Wild-Type Littermates Prevents Obesity and Associated Metabolic Disorders. Diabetes. 2018;67:1512–1523.
    • Institut National de la Santé Et de la Recherche Médicale
    • Tirets de séparation
    • L'Inserm en région Grand-Est
    Support :

    Agence Nationale de la Recherche Agrosup Dijon Fondation ARC pour la recherche sur le cancer Cent Pour Sang La Vie CHU Dijon Centre Georges François LECLERC
    Conseil Régional de Bourgogne Délégation régionale à la recherche et à la technologie Institut National du Cancer ELA Association Européenne contre les leucodystrophies EPHE : Dijon - Université de Bourgogne Faculté de Médecine de Dijon
    UFR Pharmacie - uB, Dijon Fondation de France Fondation pour la Recherche Médicale en France Laboratoire d’excellence - LipSTIC Dijon La Ligue Contre le Cancer Société française d'hématologie