Bacteria Antibiotics and Immunity
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 and France Vaccins).
Jean-Claude Sirard earned his PhD in 1995 from the University of Paris and the Pasteur Institute, where he investigated the pathogenesis of Bacillus anthracis, the bacterium responsible for anthrax (1991–1998). He subsequently completed postdoctoral training at the Swiss Institute for Experimental Cancer Research (ISREC) in Lausanne (1998–2003), studying the interactions between intestinal epithelial cells and bacterial pathogens such as Salmonella enterica.
A pioneer in identifying flagellin as a key bacterial component that activates pro-inflammatory signaling in mammals, Dr. Sirard joined the Institut Pasteur de Lille in 2003 as a laureate of the ATIPE/AVENIR Young Investigator Program. He later obtained a tenured research position at Inserm, where he established a research program focused on epithelial innate immunity.
His current work explores how immune cells and mediators contribute to host defense against respiratory infections caused by antibiotic-resistant Streptococcus pneumoniae and Klebsiella pneumoniae. His team aims to develop novel adjuvants and vaccines that boost respiratory innate immunity, with applications in both prevention and therapy of infectious diseases.
First name | Name | ORCID ID | Researcher ID |
Jean-Claude | SIRARD | ||
Christelle | FAVEEUW | ||
Christophe | CARNOY |
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Laurye | VAN MAELE | ||
Anne | ROGEL |
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Farouk | ALLOUCHE |
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Frédéric | WALLET |
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Mara | BALDRY |
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Delphine | CAYET |
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Daphnée | SOULARD |
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1. Matarazzo, L., Costa, C., Porte, R., Saliou, J.M., Figeac, M., Delahaye, F., Bonnefond, A., Kloeckner, B., Silvin, A., Ginhoux, F., et al. (2025). Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia. Mucosal Immunol 18, 257-268. 10.1016/j.mucimm.2024.11.009.
2. Laneque, L., Lambert, A., Cayet, D., Gilleron, C., Courtois, E., Cloteau, C., Broussard, C., Annic, B., Bessonnet, T., Camberlein, E., et al. (2025). Mutagenesis to Orient Conjugation and Preserve Self-adjuvant Properties of Flagellin in Conjugates. Chembiochem 26, e202401002. 10.1002/cbic.202401002.
3. Vieira Da Cruz, A., Jimenez-Castellanos, J.C., Bornsen, C., Van Maele, L., Compagne, N., Pradel, E., Muller, R.T., Meurillon, V., Soulard, D., Piveteau, C., et al. (2024). Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae. EMBO Mol Med 16, 93-111. 10.1038/s44321-023-00007-9.
4. van Linge, C.C.A., Kullberg, R.F.J., Chouchane, O., Roelofs, J., Goessens, W.H.F., van 't Veer, C., Sirard, J.C., de Vos, A.F., and van der Poll, T. (2024). Topical adjunctive treatment with flagellin augments pulmonary neutrophil responses and reduces bacterial dissemination in multidrug-resistant K. pneumoniae infection. Front Immunol 15, 1450486. 10.3389/fimmu.2024.1450486.
5. Mondeme, M., Zeroual, Y., Soulard, D., Hennart, B., Beury, D., Saliou, J.M., Carnoy, C., Sirard, J.C., and Faveeuw, C. (2024). Amoxicillin treatment of pneumococcal pneumonia impacts bone marrow neutrophil maturation and function. J Leukoc Biol 115, 463-475. 10.1093/jleuko/qiad125.
6. Maia, A.R., Cezard, A., Fouquenet, D., Vasseur, V., Briard, B., Sirard, J.C., Si-Tahar, M., and Herve, V. (2024). Preventive nasal administration of flagellin restores antimicrobial effect of gentamicin and protects against a multidrug-resistant strain of Pseudomonas aeruginosa. Antimicrob Agents Chemother, e0136123. 10.1128/aac.01361-23.
7. Liu, X., Van Maele, L., Matarazzo, L., Soulard, D., Alves Duarte da Silva, V., de Bakker, V., Denereaz, J., Bock, F.P., Taschner, M., Ou, J., et al. (2024). A conserved antigen induces respiratory Th17-mediated broad serotype protection against pneumococcal superinfection. Cell Host Microbe 32, 304-314 e308. 10.1016/j.chom.2024.02.002.
8. Creusat, F., Jouan, Y., Gonzalez, L., Barsac, E., Ilango, G., Lemoine, R., Soulard, D., Hankard, A., Boisseau, C., Guillon, A., et al. (2024). IFN-gamma primes bone marrow neutrophils to acquire regulatory functions in severe viral respiratory infections. Sci Adv 10, eadn3257. 10.1126/sciadv.adn3257.
9. Costa, C., Sirard, J.C., Gibson, P.S., Veening, J.W., Gjini, E., and Baldry, M. (2024). Triggering Toll-Like Receptor 5 Signaling During Pneumococcal Superinfection Prevents the Selection of Antibiotic Resistance. J Infect Dis 230, e1126-e1135. 10.1093/infdis/jiae239.
10. Baldry, M., Costa, C., Zeroual, Y., Cayet, D., Pardessus, J., Soulard, D., Wallet, F., Beury, D., Hot, D., MacLoughlin, R., et al. (2024). Targeted delivery of flagellin by nebulization offers optimized respiratory immunity and defense against pneumococcal pneumonia. Antimicrob Agents Chemother 68, e0086624. 10.1128/aac.00866-24.
11. van Linge, C.C.A., Hulme, K.D., Peters-Sengers, H., Sirard, J.C., Goessens, W.H.F., de Jong, M.D., Russell, C.A., de Vos, A.F., and van der Poll, T. (2023). Immunostimulatory Effect of Flagellin on MDR-Klebsiella-Infected Human Airway Epithelial Cells. Int J Mol Sci 25. 10.3390/ijms25010309.
12. Mondeme, M., Carnoy, C., Sirard, J.C., and Faveeuw, C. (2023). Treatment of Bacterial Infections with beta-Lactams: Cooperation with Innate Immunity. Infect Immun 91, e0050322. 10.1128/iai.00503-22.
13. Minhas, V., Domenech, A., Synefiaridou, D., Straume, D., Brendel, M., Cebrero, G., Liu, X., Costa, C., Baldry, M., Sirard, J.C., et al. (2023). Competence remodels the pneumococcal cell wall exposing key surface virulence factors that mediate increased host adherence. PLoS Biol 21, e3001990. 10.1371/journal.pbio.3001990.
14. Rogel, A., Ibrahim, F.M., Thirdborough, S.M., Renart-Depontieu, F., Birts, C.N., Buchan, S.L., Preville, X., King, E.V., and Al-Shamkhani, A. (2022). Fcgamma receptor-mediated cross-linking codefines the immunostimulatory activity of anti-human CD96 antibodies. JCI Insight 7. 10.1172/jci.insight.158444.
15. Fleurot, I., Lopez-Galvez, R., Barbry, P., Guillon, A., Si-Tahar, M., Bahr, A., Klymiuk, N., Sirard, J.C., and Caballero, I. (2022). TLR5 signalling is hyper-responsive in porcine cystic fibrosis airways epithelium. J Cyst Fibros 21, e117-e121. 10.1016/j.jcf.2021.08.002.
16. Dewachter, L., Denereaz, J., Liu, X., de Bakker, V., Costa, C., Baldry, M., Sirard, J.C., and Veening, J.W. (2022). Amoxicillin-resistant Streptococcus pneumoniae can be resensitized by targeting the mevalonate pathway as indicated by sCRilecs-seq. Elife 11. 10.7554/eLife.75607.
17. Belcher, T., Kammoun, H., Coutte, L., Debrie, A.S., Mielcarek, N., Sirard, J.C., Cauchi, S., and Locht, C. (2022). Live attenuated Bordetella pertussis vaccine candidate BPZE1 transiently protects against lethal pneumococcal disease in mice. Vaccine 40, 1555-1562. 10.1016/j.vaccine.2021.01.025.
18. Ramirez-Moral, I., Yu, X., Butler, J.M., van Weeghel, M., Otto, N.A., Ferreira, B.L., Maele, L.V., Sirard, J.C., de Vos, A.F., de Jong, M.D., et al. (2021). mTOR-driven glycolysis governs induction of innate immune responses by bronchial epithelial cells exposed to the bacterial component flagellin. Mucosal Immunol 14, 594-604. 10.1038/s41385-021-00377-8.
19. Qin, W., Brands, X., Van't Veer, C., A, F.d.V., Sirard, J.C., J, J.T.H.R., B, P.S., and van der Poll, T. (2021). Bronchial epithelial DNA methyltransferase 3b dampens pulmonary immune responses during Pseudomonas aeruginosa infection. PLoS Pathog 17, e1009491. 10.1371/journal.ppat.1009491.
20. Perez-Cruz, M., Kone, B., Porte, R., Carnoy, C., Tabareau, J., Gosset, P., Trottein, F., Sirard, J.C., Pichavant, M., and Gosset, P. (2021). The Toll-Like Receptor 5 agonist flagellin prevents Non-typeable Haemophilus influenzae-induced infection in cigarette smoke-exposed mice. PLoS One 16, e0236216. 10.1371/journal.pone.0236216.
21. Lopez-Galvez, R., Fleurot, I., Chamero, P., Trapp, S., Olivier, M., Chevaleyre, C., Barc, C., Riou, M., Rossignol, C., Guillon, A., et al. (2021). Airway Administration of Flagellin Regulates the Inflammatory Response to Pseudomonas aeruginosa. Am J Respir Cell Mol Biol. 10.1165/rcmb.2021-0125OC.
22. Liu, X., Kimmey, J.M., Matarazzo, L., de Bakker, V., Van Maele, L., Sirard, J.C., Nizet, V., and Veening, J.W. (2021). Exploration of Bacterial Bottlenecks and Streptococcus pneumoniae Pathogenesis by CRISPRi-Seq. Cell Host Microbe 29, 107-120 e106. 10.1016/j.chom.2020.10.001.
23. Franck, S., Michelet, R., Casilag, F., Sirard, J.C., Wicha, S.G., and 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. 10.3390/pharmaceutics13040469.
24. Casilag, F., Matarazzo, L., Franck, S., Figeac, M., Michelet, R., Kloft, C., Carnoy, C., and Sirard, J.C. (2021). The Biosynthetic Monophosphoryl Lipid A Enhances the Therapeutic Outcome of Antibiotic Therapy in Pneumococcal Pneumonia. ACS Infect Dis 7, 2164-2175. 10.1021/acsinfecdis.1c00176.
25. Assabban, A., Dubois-Vedrenne, I., Van Maele, L., Salcedo, R., Snyder, B.L., Zhou, L., Azouz, A., de Toeuf, B., Lapouge, G., La, C., et al. (2021). Tristetraprolin expression by keratinocytes protects against skin carcinogenesis. JCI Insight 6. 10.1172/jci.insight.140669.
26. Vijayan, A., Van Maele, L., Fougeron, D., Cayet, D., and Sirard, J.C. (2020). The GM-CSF Released by Airway Epithelial Cells Orchestrates the Mucosal Adjuvant Activity of Flagellin. J Immunol 205, 2873-2882. 10.4049/jimmunol.2000746.
27. Sorg, R.A., Gallay, C., Van Maele, L., Sirard, J.C., and Veening, J.W. (2020). Synthetic gene-regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae. Proc Natl Acad Sci U S A 117, 27608-27619. 10.1073/pnas.1920015117.
28. Van Maele, L., Fougeron, D., Cayet, D., Chalon, A., Piccioli, D., Collignon, C., Sirard, J.C., and Didierlaurent, A.M. (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. 10.1002/eji.201948234.
29. Matarazzo, L., Casilag, F., Porte, R., Wallet, F., Cayet, D., Faveeuw, C., Carnoy, C., and Sirard, J.C. (2019). Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia. Front Immunol 10, 723. 10.3389/fimmu.2019.00723.
30. Georgel, A.F., Cayet, D., Pizzorno, A., Rosa-Calatrava, M., Paget, C., Sencio, V., Dubuisson, J., Trottein, F., Sirard, J.C., and 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. 10.1016/j.antiviral.2019.05.002.
31. Franck, S., Fuhrmann-Selter, T., Joseph, J.F., Michelet, R., Casilag, F., Sirard, J.C., Wicha, S.G., and 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. 10.1016/j.talanta.2019.03.098.
32. Debrie, A.S., Mielcarek, N., Lecher, S., Roux, X., Sirard, J.C., and Locht, C. (2019). Early Protection against Pertussis Induced by Live Attenuated Bordetella pertussis BPZE1 Depends on TLR4. J Immunol. 10.4049/jimmunol.1901102.
33. Biedma, M.E., Cayet, D., Tabareau, J., Rossi, A.H., Ivicak-Kocjan, K., Moreno, G., Errea, A., Soulard, D., Parisi, G., Jerala, R., et al. (2019). Recombinant flagellins with deletions in domains D1, D2, and D3: Characterization as novel immunoadjuvants. Vaccine 37, 652-663. 10.1016/j.vaccine.2018.12.009.
34. Vijayan, A., Rumbo, M., Carnoy, C., and Sirard, J.C. (2018). Compartmentalized Antimicrobial Defenses in Response to Flagellin. Trends Microbiol 26, 423-435. 10.1016/j.tim.2017.10.008.
35. Beshara, R., Sencio, V., Soulard, D., Barthelemy, A., Fontaine, J., Pinteau, T., Deruyter, L., Ismail, M.B., Paget, C., Sirard, J.C., et al. (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. 10.1371/journal.ppat.1007360.
36. Klein, A., Carnoy, C., Lamblin, G., Roussel, P., van Kuik, J.A., de Waard, P., and Vliegenthart, J.F. (1991). Isolation and structural characterization of novel neutral oligosaccharide-alditols from respiratory-mucus glycoproteins of a patient suffering from bronchiectasis. 1. Structure of 11 oligosaccharides having the GlcNAc beta(1----3)Gal beta(1----4)GlcNAc beta(1----6)GalNAc-o1 structural element in common. Eur J Biochem 198, 151-168.
