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).
Jean-Claude Sirard earned his PhD in 1995 from the University of Paris and the Pasteur Institute. From 1991 to 1998, he studied the bacterial pathogenesis of Bacillus anthracis, the causative agent of anthrax. He then trained as a postdoctoral fellow at the Swiss Institute for Experimental Cancer Research (ISREC) in Lausanne (1998–2003), focusing on the interaction between intestinal epithelial cells and bacterial pathogens such as Salmonella enterica. A pioneer in the discovery of flagellin as a key bacterial component that triggers pro-inflammatory responses in mammals, he joined the Institut Pasteur de Lille in 2003 as a laureate of the Young Investigator program ATIPE/AVENIR. He subsequently secured a tenure position at Inserm to develop research on epithelial innate immunity. His team investigates the role of immune cells and mediators in host defense against respiratory infections caused by antibiotic-resistant Streptococcus pneumoniae and Klebsiella pneumoniae, with a focus on developing novel adjuvants and vaccines to enhance respiratory innate immunity for both prophylactic and therapeutic applications.
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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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.
Matarazzo, L., Costa, C., Porte, R., Saliou, J.M., Figeac, M., Delahaye, F., Bonnefond, A., Kloeckner, B., Silvin, A., Ginhoux, F., et al. (2024). Neutrophil subsets enhance the efficacy of host-directed therapy in pneumococcal pneumonia. Mucosal Immunol. 10.1016/j.mucimm.2024.11.009.
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.
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.
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. 10.1093/infdis/jiae239.
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.
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.
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.
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.
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.
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.
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.
13. 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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Porte, R., Van Maele, L., Munoz-Wolf, N., Foligne, B., Dumoutier, L., Tabareau, J., Cayet, D., Gosset, P., Jonckheere, N., Van Seuningen, I., et al. (2017). Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22. Infect Immun 85. 10.1128/IAI.00806-16.
Ghinnagow, R., De Meester, J., Cruz, L.J., Aspord, C., Corgnac, S., Macho-Fernandez, E., Soulard, D., Fontaine, J., Chaperot, L., Charles, J., et al. (2017). Co-delivery of the NKT agonist alpha-galactosylceramide and tumor antigens to cross-priming dendritic cells breaks tolerance to self-antigens and promotes antitumor responses. Oncoimmunology 6, e1339855. 10.1080/2162402X.2017.1339855.
