Bacteria Antibiotics and Immunity


Jean Claude SIRARD
INSERM research director

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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).

Axis 1-

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

Axis 2-

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

Axis 3-

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

Current Staff

CARNOY Christophe
Professor, University of Lille
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CAYET Delphine
Engineer, IPL
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CHATAGNON Jonathan
Engineer, IPL
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FAVEEUW Christelle
INSERM Researcher
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FRYDER Margot
PhD Student
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GEOGEL Anne-France
PhD, PharmD, GHICL
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GODART Celestin
PhD Student
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LI Xing
PhD Student

MATARAZZO Laura
Post Doc
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ROGEL Anne
Assistant Professor, University of Lille
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RUDANT Eva
PhD Student
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SACHET Lisa
PhD Student
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SIRARD Jean-Claude
INSERM research director
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Learn more about Jean-Claude

SOULARD Daphnée
Engineer, IPL
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VAN MAEL Laurye
INSERM researcher
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WALLET Frédéric
MD, CHU Lille
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ZEROUAL Yasmine
PhD Student 

 

 

  • BALDRY Mara
    Funding Région Hauts de France/Institut Pasteur de Lille and H2020 project FAIR (2020-2025)
    Open to work as a senior postdoc
  • CASILAG Fordiligie
    Funding: EraNet JPIAMR (2016-2018)
    Business Development Manager at PEPperPRINT GmbH in Germany (2019-present)
  • MATARAZZO Laura
    PharmD-PhD - Funding H2020 project FAIR (2020)
    Postdoc in Trinity College Dublin (2021-2022)
    Postdoc in Univ Lisbonne (2022-2024)
  • SANJUAN GARCIA Miren Itziar
    Funding H2020 project FAIR (2020-2021)
    Position of Q/C manager in the biotech company Curia in Spain (2021-present)
  • VIJAYAN Aneesh
    Funding: MSCA H2020 (2016-2018)
    Senior Scientist in the company Johnson & Johnson in the Netherlands  (2018-2024)
    Study director in the biotech company Artemis Bioservices in the Netherlands (2024-present)

• Baldry M, Caballero I, Ruuls L, Cayet D, Zeroual Y, Costa C, Beury D, Hot D, Le Vern Y, Heuze-Vourc'h N, MacLoughlin R, Benecke AG, Stockhofe-Zurwieden N, Sirard JC. 2026. Flagellin nebulization enhances respiratory immune responses in the porcine model. iScience 28:114218.

• Matarazzo L, Costa C, Porte R, Saliou JM, Figeac M, Delahaye F, Bonnefond A, Kloeckner B, Silvin A, Ginhoux F, Faveeuw C, Baldry M, Carnoy C, Sirard JC. 2025. Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia. Mucosal Immunol 18:257-268.

• Silva Angulo F, Joseph CV, Delval L, Deruyter L, Heumel S, Bicharel M, Rodrigues PB, Sencio V, Bourguignon T, Machado MG, Fourcot M, Delhaye S, Salome-Desnoulez S, Valet P, Adnot S, Wolowczuk I, Sirard JC, Pichavant M, Staels B, Haas JT, Gref R, Vandel J, Machelart A, Duez H, Pourcet B, Trottein F. 2025. Rev-erb-alpha antagonism in alveolar macrophages protects against pneumococcal infection in elderly mice. Cell Rep 44:115273.


• Negrier L, Roche M, Lannoy D, Berneron C, Pacqueu L, Carnoy C, Guillon A, Hamze B, Sirard JC, Decaudin B, Odou P, Danel C. 2025. Physicochemical stability of a polysorbate-80-containing solvent compounded in the hospital pharmacy and used to reconstitute a biologic for nebulisation. Eur J Hosp Pharm doi:10.1136/ejhpharm-2024-004441.


• Laneque L, Lambert A, Cayet D, Gilleron C, Courtois E, Cloteau C, Broussard C, Annic B, Bessonnet T, Camberlein E, Sirard JC, Grandjean C. 2025. Mutagenesis to Orient Conjugation and Preserve Self-adjuvant Properties of Flagellin in Conjugates. Chembiochem 26:e202401002.


• Mondeme M, Zeroual Y, Soulard D, Hennart B, Beury D, Saliou JM, Carnoy C, Sirard JC, Faveeuw C. 2024. Amoxicillin treatment of pneumococcal pneumonia impacts bone marrow neutrophil maturation and function. J Leukoc Biol 115:463-475.


• Liu X, Van Maele L, Matarazzo L, Soulard D, Alves Duarte da Silva V, de Bakker V, Denereaz J, Bock FP, Taschner M, Ou J, Gruber S, Nizet V, Sirard JC, Veening JW. 2024. A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection. Cell Host Microbe 32:304-314 e8.


• Costa C, Sirard JC, Gibson PS, Veening JW, Gjini E, Baldry M. 2024. Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance. J Infect Dis 230:e1126-e1135.


• Baldry M, Costa C, Zeroual Y, Cayet D, Pardessus J, Soulard D, Wallet F, Beury D, Hot D, MacLoughlin R, Heuze-Vourc'h N, Sirard JC, Carnoy C. 2024. Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia. Antimicrob Agents Chemother 68:e0086624.


• Vieira Da Cruz A, Jimenez-Castellanos JC, Bornsen C, Van Maele L, Compagne N, Pradel E, Muller RT, Meurillon V, Soulard D, Piveteau C, Biela A, Dumont J, Leroux F, Deprez B, Willand N, Pos KM, Frangakis AS, Hartkoorn RC, Flipo M. 2024. Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae. EMBO Mol Med 16:93-111.


• Mondeme M, Carnoy C, Sirard JC, Faveeuw C. 2023. Treatment of Bacterial Infections with beta-Lactams: Cooperation with Innate Immunity. Infect Immun 91:e0050322.


• Fleurot I, Lopez-Galvez R, Barbry P, Guillon A, Si-Tahar M, Bahr A, Klymiuk N, Sirard JC, Caballero I. 2022. TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium. J Cyst Fibros 21:e117-e121.


• Rogel A, Ibrahim FM, Thirdborough SM, Renart-Depontieu F, Birts CN, Buchan SL, Preville X, King EV, Al-Shamkhani A.2022. Fcgamma receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies. JCI Insight 7.


• Lopez-Galvez R, Fleurot I, Chamero P, Trapp S, Olivier M, Chevaleyre C, Barc C, Riou M, Rossignol C, Guillon A, Si-Tahar M, May T, Barbry P, Bahr A, Klymiuk N, Sirard JC, Caballero I. 2021. Airway Administration of Flagellin Regulates the Inflammatory Response to Pseudomonas aeruginosa. Am J Respir Cell Mol Biol doi:10.1165/rcmb.2021-0125OC.


• Liu X, Kimmey JM, Matarazzo L, de Bakker V, Van Maele L, Sirard JC, Nizet V, Veening JW. 2021. Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq. Cell Host Microbe 29:107-120 e6.


• Franck S, Michelet R, Casilag F, Sirard JC, Wicha SG, Kloft C. 2021. A Model-Based Pharmacokinetic/Pharmacodynamic Analysis of the Combination of Amoxicillin and Monophosphoryl Lipid A Against S. pneumoniae in Mice. Pharmaceutics 13.


• Casilag F, Matarazzo L, Franck S, Figeac M, Michelet R, Kloft C, Carnoy C, Sirard JC. 2021. The Biosynthetic Monophosphoryl Lipid A Enhances the Therapeutic Outcome of Antibiotic Therapy in Pneumococcal Pneumonia. ACS Infect Dis 7:2164-2175.


• Assabban A, Dubois-Vedrenne I, Van Maele L, Salcedo R, Snyder BL, Zhou L, Azouz A, de Toeuf B, Lapouge G, La C, Melchior M, Nguyen M, Thomas S, Wu SF, Hu W, Kruys V, Blanpain C, Trinchieri G, Gueydan C, Blackshear PJ, Goriely S. 2021. Tristetraprolin expression by keratinocytes protects against skin carcinogenesis. JCI Insight 6.


• Vijayan A, Van Maele L, Fougeron D, Cayet D, Sirard JC. 2020. The GM-CSF Released by Airway Epithelial Cells Orchestrates the Mucosal Adjuvant Activity of Flagellin. J Immunol 205:2873-2882.


• Sorg RA, Gallay C, Van Maele L, Sirard JC, Veening JW. 2020. Synthetic gene-regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae. Proc Natl Acad Sci U S A 117:27608-27619.


• Sencio V, Barthelemy A, Tavares LP, Machado MG, Soulard D, Cuinat C, Queiroz-Junior CM, Noordine ML, Salome-Desnoulez S, Deryuter L, Foligne B, Wahl C, Frisch B, Vieira AT, Paget C, Milligan G, Ulven T, Wolowczuk I, Faveeuw C, Le Goffic R, Thomas M, Ferreira S, Teixeira MM, Trottein F. 2020. Gut Dysbiosis during Influenza Contributes to Pulmonary Pneumococcal Superinfection through Altered Short-Chain Fatty Acid Production. Cell Rep 30:2934-2947 e6.


• Van Maele L, Fougeron D, Cayet D, Chalon A, Piccioli D, Collignon C, Sirard JC, Didierlaurent AM. 2019. Toll-like receptor 4 signaling in hematopoietic-lineage cells contributes to the enhanced activity of the human vaccine adjuvant AS01. Eur J Immunol 49:2134-2145.


• Matarazzo L, Casilag F, Porte R, Wallet F, Cayet D, Faveeuw C, Carnoy C, Sirard JC. 2019. Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia. Front Immunol 10:723.


• Georgel AF, Cayet D, Pizzorno A, Rosa-Calatrava M, Paget C, Sencio V, Dubuisson J, Trottein F, Sirard JC, Carnoy C. 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. Antiviral Res 168:28-35.


• Franck S, Fuhrmann-Selter T, Joseph JF, Michelet R, Casilag F, Sirard JC, Wicha SG, Kloft C. 2019. A rapid, simple and sensitive liquid chromatography tandem mass spectrometry assay to determine amoxicillin concentrations in biological matrix of little volume. Talanta 201:253-258.


• Biedma ME, Cayet D, Tabareau J, Rossi AH, Ivicak-Kocjan K, Moreno G, Errea A, Soulard D, Parisi G, Jerala R, Berguer P, Rumbo M, Sirard JC. 2019. Recombinant flagellins with deletions in domains D1, D2, and D3: Characterization as novel immunoadjuvants. Vaccine 37:652-663.


• Vijayan A, Rumbo M, Carnoy C, Sirard JC. 2018. Compartmentalized Antimicrobial Defenses in Response to Flagellin. Trends Microbiol 26:423-435.


• Beshara R, Sencio V, Soulard D, Barthelemy A, Fontaine J, Pinteau T, Deruyter L, Ismail MB, Paget C, Sirard JC, Trottein F, Faveeuw C. 2018. Alteration of Flt3-Ligand-dependent de novo generation of conventional dendritic cells during influenza infection contributes to respiratory bacterial superinfection. PLoS Pathog 14:e1007360.