FLAGELLIN AEROSOL THERAPY AS AN IMMUNOMODULATORY ADJUNCT TO THE ANTIBIOTIC TREATMENT OF DRUG-RESISTANT BACTERIAL PNEUMONIA

Información del proyecto

FAIR

Identificador del acuerdo de subvención: 847786

DOI

10.3030/847786

Fecha de la firma de la CE 6 Diciembre 2019

Fecha de inicio 1 Enero 2020

Fecha de finalización 30 Junio 2026

Financiado con arreglo a

• SOCIETAL CHALLENGES - Health, demographic change and well-being

Coste total

€ 10 162 903,75

Aportación de la UE

€ 10 162 903,75

Coordinado por

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

CORDIS proporciona enlaces a los documentos públicos y las publicaciones de los proyectos de los programas marco HORIZONTE.

Los enlaces a los documentos y las publicaciones de los proyectos del Séptimo Programa Marco, así como los enlaces a algunos tipos de resultados específicos, como conjuntos de datos y «software», se obtienen dinámicamente de OpenAIRE .

Resultado final

Websites, patent fillings, videos etc. (1)

Branding

Logo, public website

Publicaciones

Peer reviewed articles (30)

Flagellin nebulization enhances respiratory immune responses in the porcine model

Autores: Mara Baldry, Ignacio Caballero, Lisette Ruuls, Delphine Cayet, Yasmine Zeroual, Charlotte Costa, Delphine Beury, David Hot, Yves Le Vern, Nathalie Heuzé-Vourc’h, Ronan MacLoughlin, Arndt G. Benecke, Norbert Stockhofe-Zurwieden, Jean-Claude Sirard
Publicado en: iScience, Edición 28, 2026, Página(s) 114218, ISSN 2589-0042
Editor: Elsevier BV
DOI: 10.1016/j.isci.2025.114218

Differential platelet protein release profiles in community-acquired pneumonia and COVID-19

Autores: Osoul Chouchane, Valentine Léopold, Erik H.A. Michels, Justin de Brabander, Christine C.A. van Linge, Augustinus M. Klarenbeek, W. Joost Wiersinga, Cornelis van ‘t Veer, Tom van der Poll
Publicado en: ERJ Open Research, Edición 11, 2025, Página(s) 00863-2024, ISSN 2312-0541
Editor: European Respiratory Society (ERS)
DOI: 10.1183/23120541.00863-2024

Butyrate-producing gut bacterium <i>Faecalibacterium prausnitzii</i> protects against bacterial pneumonia

Autores: Robert F.J. Kullberg, Christine C.A. van Linge, Alex F. de Vos, Xanthe Brands, Thi Phuong Nam Bui, Joe M. Butler, Daniël R. Faber, Aswin Verhoeven, René M. van den Wijngaard, Wouter J. de Jonge, Max Nieuwdorp, Tom van der Poll, Bastiaan W. Haak, W. Joost Wiersinga
Publicado en: European Respiratory Journal, Edición 66, 2025, Página(s) 2402208, ISSN 0903-1936
Editor: European Respiratory Society
DOI: 10.1183/13993003.02208-2024

HIF-1a stabilizattion in flagellin-stimulated human bronchial cells impairs barrier function

Autores: Ivan Ramirez-Moral, Bianca L. Ferreira, Joe M. Butler, Michel van Weeghel, Natasja A. Otto, Alex F. de Vos, Xiao Yu, Menno D. de Jong, Riekelt H. Houtkooper, and Tom van der Poll
Publicado en: Cells, 2022, ISSN 2073-4409
Editor: MDPI
DOI: 10.3390/cells11030391

Association between age and the host response in critically ill patients with sepsis

Autores: Erik H. A. Michels, Joe M. Butler, Tom D. Y. Reijnders, Olaf L. Cremer, Brendon P. Scicluna, Fabrice Uhel, Hessel Peters-Sengers, Marcus J. Schultz, Julian C. Knight, Lonneke A. van Vught, Tom van der Poll
Publicado en: Critical Care, 2022, ISSN 1466-609X
Editor: BioMed Central
DOI: 10.1186/s13054-022-04266-9

Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia

Autores: Mara Baldry, Charlotte Costa, Yasmine Zeroual, Delphine Cayet, Jeoffrey Pardessus, Daphnée Soulard, Frédéric Wallet, Delphine Beury, David Hot, Ronan MacLoughlin, Nathalie Heuzé-Vourc’h, Jean-Claude Sirard, Christophe Carnoy
Publicado en: Antimicrobial Agents and Chemotherapy, Edición 68, 2024, ISSN 0066-4804
Editor: American Society for Microbiology
DOI: 10.1128/aac.00866-24

Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia

Autores: Laura Matarazzo, Charlotte Costa, Rémi Porte, Jean-Michel Saliou, Martin Figeac, Fabien Delahaye, Amélie Bonnefond, Benoit Kloeckner, Aymeric Silvin, Florent Ginhoux, Christelle Faveeuw, Mara Baldry, Christophe Carnoy, Jean-Claude Sirard
Publicado en: Mucosal Immunology, Edición 18, 2025, Página(s) 257-268, ISSN 1933-0219
Editor: Nature Publishing Group
DOI: 10.1016/j.mucimm.2024.11.009

The Use of Translational Modelling and Simulation to Develop Immunomodulatory Therapy as an Adjunct to Antibiotic Treatment in the Context of Pneumonia

Autores: Robin Michelet, Moreno Ursino, Sandrine Boulet, Sebastian Franck, Fiordiligie Casilag, Mara Baldry, Jens Rolff, Madelé van Dyk, Sebastian G. Wicha, Jean-Claude Sirard, Emmanuelle Comets, Sarah Zohar, Charlotte Kloft
Publicado en: Pharmaceutics, Edición 13/5, 2021, Página(s) 601, ISSN 1999-4923
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/pharmaceutics13050601

Proteomic profiling of neutrophils and plasma in community-acquired pneumonia reveals crucial proteins in diverse biological pathways linked to clinical outcome

Autores: Erik H. A. Michels, Osoul Chouchane, Justin de Brabander, Alex F. de Vos, Daniël R. Faber, Renée A. Douma, Eva R. Smit, W. Joost Wiersinga, Maartje van den Biggelaar, Tom van der Poll, Arie J. Hoogendijk
Publicado en: Frontiers in Immunology, Edición 15, 2024, ISSN 1664-3224
Editor: Frontiers Media SA
DOI: 10.3389/fimmu.2024.1470383

Human alveolar macrophages do not rely on glucose metabolism upon activation by lipopolysaccharide

Autores: Liza Pereverzeva, Christine C.A. van Linge, Alex R. Schuurman, Augustijn M. Klarenbeek, Ivan Ramirez Moral, Natasja A. Otto, Hessel Peters-Sengers, Joe M. Butler, Bauke V. Schomakers, Michel van Weeghel, Riekelt H. Houtkooper, W. Joost Wiersinga, Peter I. Bonta, Jouke T. Annema, Alex F. de Vos, Tom van der Poll
Publicado en: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Edición 1868, 2025, Página(s) 166488, ISSN 0925-4439
Editor: Elsevier BV
DOI: 10.1016/j.bbadis.2022.166488

mTOR inhibition impacts the flagellin-augmented inflammatory and antimicrobial response of human airway epithelial cells to Pseudomonas aeruginosa

Autores: Christine C.A. van Linge, Katina D. Hulme, Hessel Peters-Sengers, Robert F.J. Kullberg, Menno D. de Jong, Colin A. Russell, Alex F. de Vos, Tom van der Poll
Publicado en: PLOS One, Edición 20, 2025, Página(s) e0321462, ISSN 1932-6203
Editor: Public Library of Science
DOI: 10.1371/journal.pone.0321462

Straightforward Phase I Dose-Finding Design for Healthy Volunteers Accounting for Surrogate Activity Biomarkers

Autores: Sandrine Boulet, Emmanuelle Comets, Antoine Guillon, Linda B.S. Aulin, Robin Michelet, Charlotte Kloft, Sarah Zohar, Moreno Ursino
Publicado en: Statistics in Biopharmaceutical Research, Edición 17, 2025, Página(s) 496-505, ISSN 1946-6315
Editor: Informa UK Limited
DOI: 10.1080/19466315.2024.2416410

Topical adjunctive treatment with flagellin augments pulmonary neutrophil responses and reduces bacterial dissemination in multidrug-resistant K. pneumoniae infection

Autores: Christine C. A. van Linge, Robert F.J. Kullberg, Osoul Chouchane, Joris J. T. H. Roelofs, Wil H. F. Goessens, Cornelis van ‘t Veer, Jean-Claude Sirard, Alex F. de Vos, Tom van der Poll
Publicado en: Frontiers in Immunology, Edición 15, 2024, ISSN 1664-3224
Editor: Frontiers Media SA
DOI: 10.3389/fimmu.2024.1450486

Bayesian framework for multi-source data integration-Application to human extrapolation from preclinical studies

Autores: Sandrine Boulet, Moreno Ursino, Robin Michelet, Linda BS Aulin, Charlotte Kloft, Emmanuelle Comets, Sarah Zohar
Publicado en: Statistical Methods in Medical Research, Edición 33, 2024, Página(s) 574-588, ISSN 0962-2802
Editor: SAGE Publications
DOI: 10.1177/09622802241231493

Host Response Changes and Their Association with Mortality in COVID-19 Patients with Lymphopenia

Autores: Erik H. A. Michels, Brent Appelman, Justin de Brabander, Rombout B. E. van Amstel, Christine C. A. van Linge, Osoul Chouchane, Tom D. Y. Reijnders, Alex R. Schuurman, Titia A. L. Sulzer, Augustijn M. Klarenbeek, Renée A. Douma, Lieuwe D. J. Bos, W. Joost Wiersinga, Hessel Peters-Sengers, Tom van der Poll, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Floor van Baarle, Martijn Beudel, Har
Publicado en: American Journal of Respiratory and Critical Care Medicine, Edición 209, 2024, Página(s) 402-416, ISSN 1073-449X
Editor: American Thoracic Society
DOI: 10.1164/rccm.202305-0890oc

The blood transcriptional response in patients developing intensive care unit-acquired pneumonia

Autores: Justin de Brabander, Erik H.A. Michels, Joe M. Butler, Tom D.Y. Reijnders, Tjitske S.R. van Engelen, Giuseppe G.F. Leite, Fleur P. Paling, Augustijn M. Klarenbeek, Daoud L.S. Sie, Roxane E. Boyer, Timothy E. Sweeney, Marc J.M. Bonten, Leen Timbermont, Surbhi Malhotra-Kumar, Jan A.J.W. Kluytmans, Hessel Peters-Sengers, Tom van der Poll
Publicado en: European Respiratory Journal, Edición 65, 2025, Página(s) 2400592, ISSN 0903-1936
Editor: European Respiratory Society
DOI: 10.1183/13993003.00592-2024

Uncovering metabolic pathways in human alveolar macrophages in response to lipopolysaccharide

Autores: Christine C A van Linge, Erik H A Michels, Liza Pereverzeva, Regina de Beer, Augustijn M Klarenbeek, Bauke V Schomakers, Michel van Weeghel, Riekelt H Houtkooper, W Joost Wiersinga, Peter I Bonta, Jouke T Annema, Tom van der Poll, Alex F de Vos
Publicado en: Clinical and Experimental Immunology, Edición 219, 2025, ISSN 0009-9104
Editor: Blackwell Publishing Inc.
DOI: 10.1093/cei/uxaf028

Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance

Autores: Charlotte Costa, Jean-Claude Sirard, Paddy S Gibson, Jan-Willem Veening, Erida Gjini, Mara Baldry
Publicado en: The Journal of Infectious Diseases, 2024, ISSN 0022-1899
Editor: University of Chicago Press
DOI: 10.1093/infdis/jiae239

Platelets of COVID-19 patients display mitochondrial dysfunction, oxidative stress, and energy metabolism failure compatible with cell death

Autores: Valentine Léopold, Osoul Chouchane, Joe M. Butler, Alex R. Schuurman, Erik H.A. Michels, Justin de Brabander, Bauke V. Schomakers, Michel van Weeghel, Daisy I. Picavet-Havik, Anita E. Grootemaat, Renée A. Douma, Tom D.Y. Reijnders, Augustijn M. Klarenbeek, Brent Appelman, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Floor van Baarle, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Pet
Publicado en: Research and Practice in Thrombosis and Haemostasis, Edición 7, 2025, Página(s) 102213, ISSN 2475-0379
Editor: Elsevier BV
DOI: 10.1016/j.rpth.2023.102213

Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of <i>Pseudomonas aeruginosa</i>

Autores: Ana Raquel Maia, Adeline Cezard, Delphine Fouquenet, Virginie Vasseur, Benoit Briard, Jean-Claude Sirard, Mustapha Si-Tahar, Virginie Hervé
Publicado en: Antimicrobial Agents and Chemotherapy, Edición 68, 2024, ISSN 0066-4804
Editor: American Society for Microbiology
DOI: 10.1128/aac.01361-23

Age-related changes in plasma biomarkers and their association with mortality in COVID-19

Autores: Erik H.A. Michels, Brent Appelman, Justin de Brabander, Rombout B.E. van Amstel, Osoul Chouchane, Christine C.A. van Linge, Alex R. Schuurman, Tom D.Y. Reijnders, Titia A.L. Sulzer, Augustijn M. Klarenbeek, Renée A. Douma, Lieuwe D.J. Bos, W. Joost Wiersinga, Hessel Peters-Sengers, Tom van der Poll, Michiel van Agtmael, Anne Geke Algera, Brent Appelman, Floor van Baarle, Martijn Beudel, Harm Jan
Publicado en: European Respiratory Journal, Edición 62, 2024, Página(s) 2300011, ISSN 0903-1936
Editor: European Respiratory Society
DOI: 10.1183/13993003.00011-2023

Thrombocytopenia is associated with a dysregulated host response in severe COVID-19

Autores: Brent Appelman, Erik H.A. Michels, Justin de Brabander, Hessel Peters-Sengers, Rombout B.E. van Amstel, Sophie M. Noordzij, Augustijn M. Klarenbeek, Christine C.A. van Linge, Osoul Chouchane, Alex R. Schuurman, Tom D.Y. Reijnders, Renée A. Douma, Lieuwe D.J. Bos, W. Joost Wiersinga, Tom van der Poll
Publicado en: Thrombosis Research, Edición 229, 2025, Página(s) 187-197, ISSN 0049-3848
Editor: Pergamon Press
DOI: 10.1016/j.thromres.2023.07.008

The Plasma Proteome in Community-acquired Pneumonia: Pathophysiology, Outcome, and 10-Year Risk

Autores: Erik H. A. Michels, Hessel Peters-Sengers, Justin de Brabander, Alex R. Schuurman, Tom D. Y. Reijnders, Bastiaan W. Haak, Xanthe Brands, Sebastiaan C. M. Joosten, Daniël R. Faber, Olaf L. Cremer, Renée A. Douma, Alex F. de Vos, W. Joost Wiersinga, Joe M. Butler, Tom van der Poll
Publicado en: American Journal of Respiratory and Critical Care Medicine, Edición 211, 2026, Página(s) 2180-2190, ISSN 1073-449X
Editor: American Thoracic Society
DOI: 10.1164/rccm.202502-0325oc

Immunostimulatory Effect of Flagellin on MDR-Klebsiella-Infected Human Airway Epithelial Cells

Autores: Christine C. A. van Linge, Katina D. Hulme, Hessel Peters-Sengers, Jean-Claude Sirard, Wil H. F. Goessens, Menno D. de Jong, Colin A. Russell, Alex F. de Vos, Tom van der Poll
Publicado en: International Journal of Molecular Sciences, Edición 25, 2023, Página(s) 309, ISSN 1422-0067
Editor: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms25010309

Inflammatory and glycolytic programs underpin a primed blood neutrophil state in patients with pneumonia

Autores: Alex R. Schuurman, Joe M. Butler, Erik H.A. Michels, Natasja A. Otto, Xanthe Brands, Bastiaan W. Haak, Fabrice Uhel, Augustijn M. Klarenbeek, Daniël R. Faber, Bauke V. Schomakers, Michel van Weeghel, Alex F. de Vos, Brendon P. Scicluna, Riekelt H. Houtkooper, W. Joost Wiersinga, Tom van der Poll
Publicado en: iScience, Edición 26, 2024, Página(s) 107181, ISSN 2589-0042
Editor: Elsevier BV
DOI: 10.1016/j.isci.2023.107181

The proteomic landscape of blood monocytes in community-acquired pneumonia

Autores: Osoul Chouchane, Erik H.A. Michels, Giuseppe G.F. Leite, Alex F. de Vos, Justin de Brabander, Joe M. Butler, Xanthe Brands, Bastiaan W. Haak, Augustijn M. Klarenbeek, W. Joost Wiersinga, Brendon P. Scicluna, Cornelis van ’t Veer, Kathrine F. Kaas, Valdemaras Petrosius, Erwin M. Schoof, Tom van der Poll
Publicado en: European Respiratory Journal, Edición 66, 2025, Página(s) 2500335, ISSN 0903-1936
Editor: European Respiratory Society
DOI: 10.1183/13993003.00335-2025

Monocyte state 1 (MS1) cells in critically ill patients with sepsis or non-infectious conditions: association with disease course and host response

Autores: Giuseppe G. F. Leite, Justin de Brabander, Erik H. A. Michels, Joe M. Butler, Olaf L. Cremer, Brendon P. Scicluna, Timothy E. Sweeney, Miguel Reyes, Reinaldo Salomao, Hessel Peters-Sengers, Tom van der Poll
Publicado en: Critical Care, Edición 28, 2024, ISSN 1364-8535
Editor: Springer Science and Business Media LLC
DOI: 10.1186/s13054-024-04868-5

Single-cell transcriptomics reveals subset-specific metabolic profiles underpinning the bronchial epithelial response to flagellin

Autores: Ivan Ramirez-Moral, Alex R. Schuurman, Christine C.A. van Linge, Joe M. Butler, Xiao Yu, Karen de Haan, Sarah van Leeuwen, Alex F. de Vos, Menno D. de Jong, Felipe A. Vieira Braga, Tom van der Poll
Publicado en: iScience, Edición 27, 2025, Página(s) 110662, ISSN 2589-0042
Editor: Elsevier BV
DOI: 10.1016/j.isci.2024.110662

Association between dexamethasone treatment and the host response in COVID-19 patients admitted to the general ward

Autores: Justin de Brabander, Erik H. A. Michels, Christine C. A. van Linge, Osoul Chouchane, Renée A. Douma, Tom D. Y. Reijnders, Alex R. Schuurman, Tjitske S. R. van Engelen, null null, Michiel A. van Agtmael, Anne Geke Algera, Brent Appelman, Frank E. H. P. van Baarle, Diane J. C. Bax, Martijn Beudel, Harm Jan Bogaard, Marije Bomers, Peter I. Bonta, Lieuwe D. J. Bos, Michela Botta, Justin de Brabander,
Publicado en: Respiratory Research, Edición 23, 2022, ISSN 1465-993X
Editor: Springer Science and Business Media LLC
DOI: 10.1186/s12931-022-02060-3

Amoxicillin-resistant Streptococcus pneumoniae can be resensitized by targeting the mevalonate pathway as indicated by sCRilecs-seq

Autores: """ Liselot Dewachter, Julien Dénéréaz, Xue Liu, Vincent de Bakker, Charlotte Costa, Mara Baldry, Jean-Claude Sirard, Jan-Willem Veening"""
Publicado en: Elife, 2022, ISSN 2050-084X
Editor: eLife Sciences Publications
DOI: 10.7554/elife.75607

Other (2)

Local tolerance and innate immune activation of primary human respiratory cells exposed to flagellin

Autores: Guy Barbin, Itziar Sanjuán-García, Mireille Caul-Futy, Christine Caul-Futy, Cindia Ferreira Lopes, Rosy Bonfante, Edouard Sage, Anne-Sophie Lacoste, Jean-Michel Saliou, Delphine Cayet, Ronan MacLoughlin, Mara Baldry, Charlotte Green-Jensen, Arndt G Benecke, Nathalie Heuze Vourc’h, Song Huang, Jean-Claude Sirard, Samuel Constant
Publicado en: 2025
Editor: openRxiv
DOI: 10.64898/2025.12.19.695341

Flagellin-mediated TLR5 activation enhances innate immune responses in healthy and diseased human airway epithelium

Autores: Xing Li, Delphine Cayet, Yasmine Zeroual, Itziar Sanjuán-García, Amélie Bonnefond, Mehdi Derhourhi, Mireille Caul-Futy, Christine Caul-Futy, Tom van der Poll, Christophe Carnoy, Mara Baldry, Samuel Constant, Jean-Claude Sirard
Publicado en: 2026
Editor: openRxiv
DOI: 10.1101/2025.11.06.686934