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

Project Information

FAIR

Grant agreement ID: 847786

DOI

10.3030/847786

EC signature date 6 December 2019

Start date 1 January 2020

End date 30 June 2026

Funded under

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

Total cost

€ 10 162 903,75

EU contribution

€ 10 162 903,75

Coordinated by

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Deliverables

Websites, patent fillings, videos etc. (1)

Branding

Logo, public website

Publications

Peer reviewed articles (30)

Flagellin nebulization enhances respiratory immune responses in the porcine model

Author(s): 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
Published in: iScience, Issue 28, 2026, Page(s) 114218, ISSN 2589-0042
Publisher: Elsevier BV
DOI: 10.1016/j.isci.2025.114218

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

Author(s): 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
Published in: ERJ Open Research, Issue 11, 2025, Page(s) 00863-2024, ISSN 2312-0541
Publisher: European Respiratory Society (ERS)
DOI: 10.1183/23120541.00863-2024

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

Author(s): 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
Published in: European Respiratory Journal, Issue 66, 2025, Page(s) 2402208, ISSN 0903-1936
Publisher: European Respiratory Society
DOI: 10.1183/13993003.02208-2024

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

Author(s): 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
Published in: Cells, 2022, ISSN 2073-4409
Publisher: MDPI
DOI: 10.3390/cells11030391

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

Author(s): 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
Published in: Critical Care, 2022, ISSN 1466-609X
Publisher: BioMed Central
DOI: 10.1186/s13054-022-04266-9

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

Author(s): 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
Published in: Antimicrobial Agents and Chemotherapy, Issue 68, 2024, ISSN 0066-4804
Publisher: American Society for Microbiology
DOI: 10.1128/aac.00866-24

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

Author(s): 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
Published in: Mucosal Immunology, Issue 18, 2025, Page(s) 257-268, ISSN 1933-0219
Publisher: 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

Author(s): 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
Published in: Pharmaceutics, Issue 13/5, 2021, Page(s) 601, ISSN 1999-4923
Publisher: 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

Author(s): 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
Published in: Frontiers in Immunology, Issue 15, 2024, ISSN 1664-3224
Publisher: Frontiers Media SA
DOI: 10.3389/fimmu.2024.1470383

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

Author(s): 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
Published in: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Issue 1868, 2025, Page(s) 166488, ISSN 0925-4439
Publisher: 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

Author(s): 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
Published in: PLOS One, Issue 20, 2025, Page(s) e0321462, ISSN 1932-6203
Publisher: Public Library of Science
DOI: 10.1371/journal.pone.0321462

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

Author(s): Sandrine Boulet, Emmanuelle Comets, Antoine Guillon, Linda B.S. Aulin, Robin Michelet, Charlotte Kloft, Sarah Zohar, Moreno Ursino
Published in: Statistics in Biopharmaceutical Research, Issue 17, 2025, Page(s) 496-505, ISSN 1946-6315
Publisher: 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

Author(s): 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
Published in: Frontiers in Immunology, Issue 15, 2024, ISSN 1664-3224
Publisher: Frontiers Media SA
DOI: 10.3389/fimmu.2024.1450486

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

Author(s): Sandrine Boulet, Moreno Ursino, Robin Michelet, Linda BS Aulin, Charlotte Kloft, Emmanuelle Comets, Sarah Zohar
Published in: Statistical Methods in Medical Research, Issue 33, 2024, Page(s) 574-588, ISSN 0962-2802
Publisher: SAGE Publications
DOI: 10.1177/09622802241231493

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

Author(s): 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
Published in: American Journal of Respiratory and Critical Care Medicine, Issue 209, 2024, Page(s) 402-416, ISSN 1073-449X
Publisher: American Thoracic Society
DOI: 10.1164/rccm.202305-0890oc

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

Author(s): 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
Published in: European Respiratory Journal, Issue 65, 2025, Page(s) 2400592, ISSN 0903-1936
Publisher: European Respiratory Society
DOI: 10.1183/13993003.00592-2024

Uncovering metabolic pathways in human alveolar macrophages in response to lipopolysaccharide

Author(s): 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
Published in: Clinical and Experimental Immunology, Issue 219, 2025, ISSN 0009-9104
Publisher: Blackwell Publishing Inc.
DOI: 10.1093/cei/uxaf028

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

Author(s): Charlotte Costa, Jean-Claude Sirard, Paddy S Gibson, Jan-Willem Veening, Erida Gjini, Mara Baldry
Published in: The Journal of Infectious Diseases, 2024, ISSN 0022-1899
Publisher: 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

Author(s): 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
Published in: Research and Practice in Thrombosis and Haemostasis, Issue 7, 2025, Page(s) 102213, ISSN 2475-0379
Publisher: 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>

Author(s): Ana Raquel Maia, Adeline Cezard, Delphine Fouquenet, Virginie Vasseur, Benoit Briard, Jean-Claude Sirard, Mustapha Si-Tahar, Virginie Hervé
Published in: Antimicrobial Agents and Chemotherapy, Issue 68, 2024, ISSN 0066-4804
Publisher: American Society for Microbiology
DOI: 10.1128/aac.01361-23

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

Author(s): 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
Published in: European Respiratory Journal, Issue 62, 2024, Page(s) 2300011, ISSN 0903-1936
Publisher: European Respiratory Society
DOI: 10.1183/13993003.00011-2023

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

Author(s): 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
Published in: Thrombosis Research, Issue 229, 2025, Page(s) 187-197, ISSN 0049-3848
Publisher: Pergamon Press
DOI: 10.1016/j.thromres.2023.07.008

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

Author(s): 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
Published in: American Journal of Respiratory and Critical Care Medicine, Issue 211, 2026, Page(s) 2180-2190, ISSN 1073-449X
Publisher: American Thoracic Society
DOI: 10.1164/rccm.202502-0325oc

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

Author(s): 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
Published in: International Journal of Molecular Sciences, Issue 25, 2023, Page(s) 309, ISSN 1422-0067
Publisher: Multidisciplinary Digital Publishing Institute (MDPI)
DOI: 10.3390/ijms25010309

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

Author(s): 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
Published in: iScience, Issue 26, 2024, Page(s) 107181, ISSN 2589-0042
Publisher: Elsevier BV
DOI: 10.1016/j.isci.2023.107181

The proteomic landscape of blood monocytes in community-acquired pneumonia

Author(s): 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
Published in: European Respiratory Journal, Issue 66, 2025, Page(s) 2500335, ISSN 0903-1936
Publisher: 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

Author(s): 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
Published in: Critical Care, Issue 28, 2024, ISSN 1364-8535
Publisher: 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

Author(s): 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
Published in: iScience, Issue 27, 2025, Page(s) 110662, ISSN 2589-0042
Publisher: 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

Author(s): 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,
Published in: Respiratory Research, Issue 23, 2022, ISSN 1465-993X
Publisher: 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

Author(s): """ Liselot Dewachter, Julien Dénéréaz, Xue Liu, Vincent de Bakker, Charlotte Costa, Mara Baldry, Jean-Claude Sirard, Jan-Willem Veening"""
Published in: Elife, 2022, ISSN 2050-084X
Publisher: eLife Sciences Publications
DOI: 10.7554/elife.75607

Other (2)

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

Author(s): 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
Published in: 2025
Publisher: openRxiv
DOI: 10.64898/2025.12.19.695341

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

Author(s): 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
Published in: 2026
Publisher: openRxiv
DOI: 10.1101/2025.11.06.686934