Université de Lille – CNRS UMR 9017 – Inserm U1019 – Institut Pasteur de Lille – CHU de Lille
The team aims to understand the molecular and cellular interactions between pneumonia-causing bacteria and the respiratory immune system while developing innovative immuno-interventions to combat bacterial pneumonia, particularly in the face of antibiotic resistance and antigen variation. A first research axis is identifying virulence factors of S. pneumoniae and K. pneumoniae and understanding host immune responses, particularly the role of myeloid cells in infection control and elimination (EU project NOSEVAC). Myeloid cell development and activation during nasal carriage, pneumonia, and pneumosepsis are critical areas of investigation, with the goal of identifying novel therapeutic targets. The team also explores immune-modulating drugs, such as innate immunity agonists, to enhance host defense mechanisms against antibiotic-resistant bacteria (EU project FAIR). Combining these with antibiotics may provide a synergistic “double-hit” strategy for pathogen clearance while promoting tissue repair. Lastly, the team aim to develop infection-preventing mucosal vaccines targeting nasopharyngeal carriage and pneumonia, addressing current vaccine limitations and reducing bacterial transmission, thus contributing to the global fight against antimicrobial resistance (EU project NOSEVAC).
Projets
Identify virulence factors of S. pneumoniae and K. pneumoniae and myeloid cell-associated protective innate immune responses
The aim is to identify bacterial factors essential for airway colonization and characterize host innate immune responses to S. pneumoniae and K. pneumoniae. Using transcriptomics, proteomics, and CRISPRi-seq in animal and human models, the study will pinpoint conserved bacterial proteins critical for nasal and lung
colonization. Functional studies will assess their role in infection and disease progression. Additionally, multiOmics and systems biology approaches will elucidate immune responses in infected tissues.
Principal investigators: Christelle Faveeuw, Laurye Van Maele, Jean-Claude Sirard
Develop targeted immunotherapies to treat bacterial pneumonia
This research aims to enhance immune defense against bacterial pneumonia by combining innate immune stimulators with antibiotics to improve pathogen clearance and combat antibiotic resistance. The team is developing a flagellin aerosol therapy (FLAMOD) to complement antibiotics for drug-resistant pneumonia, assessing its efficacy in animal models and a phase 1 clinical trial. Additionally, the research aims to stimulate IL-17 and IL-22 production in the airways by targeting dendritic cells with a monoclonal antibody and recombinant flagellin. This strategy will be tested in models of K. pneumoniae and S. pneumoniae infections, with a focus on enhancing bacterial clearance and evaluating combination treatments with antibiotics.
Principal investigators: Laurye Van Maele, Jean-Claude Sirard, Christelle Faveeuw
Produce next-generation respiratory adjuvants and vaccines against nasopharyngeal carriage and pneumonia
This research focuses on developing innovative nasal vaccines to prevent respiratory infections, including S. pneumoniae, by targeting the nasal and lung tissue, which contain key immune components tissue-resident memory T and B lymphocytes. Unlike traditional vaccines that induce systemic immunity, nasal vaccines stimulate local immune responses at the site of infection. The project will identify key immune drivers in the airways and evaluate vaccine efficacy using antigens identified in axis 1.
Principal investigators: Anne Rogel, Christophe Carnoy, Laurye Van Maele, Jean-Claude Sirard
Membres
FRYDER Margot
PhD Student
GODART Celestin
PhD Student
LI Xing
Étudiante en thèse, iSite, Univ Lille
RUDANT Eva
PhD Student
SACHET Lisa
PhD Student
Daphnée SOULARD
Chargée d’études, IPL
WALLET Frédéric
Médecin biologiste, CHU Lille
ZEROUAL Yasmine
PhD Student
Contact d'équipe
Publications
iScience 28:114218.
(2026) Flagellin nebulization enhances respiratory immune responses in the porcine model.
Mucosal Immunol 18:257-268
2025. Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia.
Cell Rep 44:115273.
2025. Rev-erb-alpha antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice.
Eur J Hosp Pharm doi:10.1136/ejhpharm-2024-004441.
. 2025. Physicochemical stability of a polysorbate-80-containing solvent compounded in the hospital pharmacy and used to reconstitute a biologic for nebulisation.
Chembiochem 26:e202401002.
2025. Mutagenesis to Orient Conjugation and Preserve Self-adjuvant Properties of Flagellin in Conjugates.
J Leukoc Biol 115:463-475.
2024. Amoxicillin treatment of pneumococcal pneumonia impacts bone marrow neutrophil maturation and function.
Cell Host Microbe 32:304-314 e8.
2024. A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection.
J Infect Dis 230:e1126-e1135.
2024. Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance.
Antimicrob Agents Chemother 68:e0086624.
2024. Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia.
EMBO Mol Med 16:93-111.
2024. Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae.
Infect Immun 91:e0050322.
2023. Treatment of Bacterial Infections with beta-Lactams: Cooperation with Innate Immunity.
J Cyst Fibros 21:e117-e121.
2022. TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium
JCI Insight 7.
2022. Fcgamma receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies.
Am J Respir Cell Mol Biol doi:10.1165/rcmb.2021-0125OC.
2021. Airway Administration of Flagellin Regulates the Inflammatory Response to Pseudomonas aeruginosa.
Cell Host Microbe 29:107-120 e6.
2021. Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq.
Pharmaceutics 13.
2021. A Model-Based Pharmacokinetic/Pharmacodynamic Analysis of the Combination of Amoxicillin and Monophosphoryl Lipid A Against S. pneumoniae in Mice.
ACS Infect Dis 7:2164-2175.
2021. The Biosynthetic Monophosphoryl Lipid A Enhances the Therapeutic Outcome of Antibiotic Therapy in Pneumococcal Pneumonia.
JCI Insight 6.
2021. Tristetraprolin expression by keratinocytes protects against skin carcinogenesis.
J Immunol 205:2873-2882.
2020. The GM-CSF Released by Airway Epithelial Cells Orchestrates the Mucosal Adjuvant Activity of Flagellin.
Proc Natl Acad Sci U S A 117:27608-27619.
2020. Synthetic gene-regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae.
Cell Rep 30:2934-2947 e6.
2020. Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production.
Eur J Immunol 49:2134-2145.
2019. Toll-like receptor 4 signaling in hematopoietic-lineage cells contributes to the enhanced activity of the human vaccine adjuvant AS01.
Front Immunol 10:723.
2019. Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia.
Antiviral Res 168:28-35.
2019. Toll-like receptor 5 agonist flagellin reduces influenza A virus replication independently of type I interferon and interleukin 22 and improves antiviral efficacy of oseltamivir.
Talanta 201:253-258.
2019. A rapid, simple and sensitive liquid chromatography tandem mass spectrometry assay to determine amoxicillin concentrations in biological matrix of little volume.
Vaccine 37:652-663.
2019. Recombinant flagellins with deletions in domains D1, D2, and D3: Characterization as novel immunoadjuvants.
Trends Microbiol 26:423-435.
2018. Compartmentalized Antimicrobial Defenses in Response to Flagellin.
PLoS Pathog 14:e1007360.
