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    How to increase pathogen resistance and tissue resilience in murine models of Influenza and Pseudomonas aeruginosa lung infections?

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    Séminaire de l'Institut Cochin

    Lundi 16 décembre 2019 - 12h00 - Salle de conférence Rosalind Franklin, 2ème étage

     


    Jean-Michel Sallenave

    Inserm UMR1152, Paris

     

     invité par Florence Niedergang

    Institut Cochin, 22 rue Méchain, 75014 Paris

     

    Résumé

    Individuals with impaired lung immune responses, such as ventilated patients in hospital, and cystic fibrosis patients are often infected with Pseudomonas aeruginosa (P.a) bacteria, and co-infection with Influenza virus (IAV) is often present. It has been known for many years that infection with IAV predisposes the host to secondary bacterial infections (such as  S.pneumoniae or S.aureus), and mechanistic studies abound, including those studying the role of desentization of TLR signalling, type I IFN- mediated impairment of neutrophil chemokines and antimicrobial production, attenuation of IL1b production etc...  However, the mechanisms underlying sensitivity to P.a after IAV infection have never been deciphered previously.

    We will address here in mice models ‘therapeutic’ options to increase anti-microbial resistance and tissue resilience in singly, or dually- infected individuals, as well as prophylactic strategies using silver nanoparticles as lung mucosal adjuvants. 

     

    Quelques publications

    Sanchez-Guzman D, Le Guen P, Villeret B, Sola N, Le Borgne R, Guyard A, Kemmel A, Crestani B, Sallenave JM, Garcia-Verdugo I. Silver nanoparticle-adjuvanted vaccine protects against lethal influenza infection through inducing BALT and IgA-mediated mucosal immunity. Biomaterials. 2019;217:doi: 10.1016/j.biomaterials.2019.119308.

    Bastaert F, Kheir S, Saint-Criq V, Villeret B, Dang PM, El-Benna J, Sirard JC, Voulhoux R, Sallenave JM. Pseudomonas aeruginosa LasB Subverts Alveolar Macrophage Activity by Interfering With Bacterial Killing Through Downregulation of Innate Immune Defense, Reactive Oxygen Species Generation, and Complement Activation. Front Immunol. 2018;9:1675. doi: 10.3389/fimmu.2018.01675.

    Villeret B, Dieu A, Straube M, Solhonne B, Miklavc P, Hamadi S, Le Borgne R, Mailleux A, Norel X, Aerts J, Diallo D, Rouzet F, Dietl P, Sallenave JM, Garcia-Verdugo I. Silver Nanoparticles Impair Retinoic Acid-Inducible Gene I-Mediated Mitochondrial Antiviral Immunity by Blocking the Autophagic Flux in Lung Epithelial Cells. ACS Nano. 2018;12:1188-1202

    Saint-Criq V, Villeret B, Bastaert F, Kheir S, Hatton A, Cazes A, Xing Z, Sermet-Gaudelus I, Garcia-Verdugo I, Edelman A, Sallenave JM. Pseudomonas aeruginosa LasB protease impairs innate immunity in mice and humans by targeting a lung epithelial cystic fibrosis transmembrane regulator-IL-6-antimicrobial-repair pathway. Thorax. 2018;73:49-61

    Roussilhon C, Bang G, Bastaert F, Solhonne B, Garcia-Verdugo I, Peronet R, Druilhe P, Sakuntabhai A, Mecheri S, Sallenave JM. The antimicrobial molecule trappin-2/elafin has anti-parasitic properties and is protective in vivo in a murine model of cerebral malaria. Sci Rep. 2017;7:42243. doi: 10.1038/srep42243.

    Le Gars M, Descamps D, Roussel D, Saussereau E, Guillot L, Ruffin M, Tabary O, Hong SS, Boulanger P, Paulais M, Malleret L, Belaaouaj A, Edelman A, Huerre M, Chignard M, Sallenave JM. Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo. Am J Respir Crit Care Med. 2013;187:170-9.

    Descamps D, Le Gars M, Balloy V, Barbier D, Maschalidi S, Tohme M, Chignard M, Ramphal R, Manoury B, Sallenave JM. Toll-like receptor 5 (TLR5), IL-1β secretion, and asparagine endopeptidase are critical factors for alveolar macrophage phagocytosis and bacterial killing. Proc Natl Acad Sci U S A. 2012;109:1619-24. 

     

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