CV Science

Jean-Claude Sirard PhD Microbiology

Course and current status

Current position

• Team leader in the Centre for infection and Immunity of Lille at the Institut Pasteur de Lille

Education

• 1997        Diploma of General Immunology (Institut Pasteur, Paris)
• 1995        PhD in Microbiology (Institut Pasteur, Paris - University Paris 6)

Positions

• 2010                    DR2 INSERM (Research Director)
• 2004                    CR1 INSERM (Senior Scientist)
• 2003-2006           Avenir team leader at the Institut Pasteur de Lille
• 1998-2003           Post-doctoral fellow at ISREC, Switzerland. Director : Pr. Kraehenbuhl

Recent grants 

• 2006-2009   FP6 STREP-INCO « Novel Therapeutic and Prophylactic Strategies to Control Mucosal Infections by South American Bacterial Strains, SavinMucoPath
• 2009-2011   Maturation funds from Inserm-Transfert ”MucoFlag: Development of recombinant flagellins as mucosal functional molecules to control respiratory infections”
• 2011-2012   FP7 support from Transvac Infrastructure on ”Transcriptional analysis of flagellin-mediated adjuvant activity” and "From mice to appropriate model of human intradermal immunization: efficacy and signature of the TLR5 agonist flagellin in Sus scrofa pigs"
• 2016-2018   JPIAMR “Repurposing disused antibiotics with immune modulators as antimicrobial strategy for respiratory tract infections”
• 2017-2020   ANR "Targeting lung epithelial cells or type 3 innate lymphoid cells for the treatment of respiratory infections Klebsiella pneumoniae"
• 2020-2024   H2020 SC1 project "Flagellin aerosol therapy as an immunomodulatory adjunct to the antibiotic treatment of drug-resistant bacterial pneumonia"

Significant publications 

1. Matarazzo L, Casilag F, Porte R, Wallet F, Cayet D, Faveeuw C, Carnoy C, Sirard JC. Therapeutic Synergy Between Antibiotics and Pulmonary Toll-Like Receptor 5 Stimulation in Antibiotic-Sensitive or -Resistant Pneumonia. Front Immunol. 2019;10:723
2. Biedma ME, Cayet D, Tabareau J, Rossi AH, Ivičak-Kocjan K, Moreno G, Errea A, Soulard D, Parisi G, Jerala R, Berguer P, Rumbo M, Sirard JC. Recombinant flagellins with deletions in domains D1, D2, and D3: Characterization as novel immunoadjuvants. Vaccine. 2019;37:652-663.
3. Vijayan A, Rumbo M, Carnoy C, Sirard JC. Compartmentalized antimicrobial defenses in response to flagellin. Trends Microbiol. 2018;26(5):423-435.
4. Fougeron D, Van Maele L, Songhet P, Cayet D, Hot D, Van Rooijen N, Mollenkopf HJ, Hardt WD, Benecke AG, Sirard JC. Indirect Toll-like receptor 5-mediated activation of conventional dendritic cells promotes the mucosal adjuvant activity of flagellin in the respiratory tract. Vaccine. 2015;33(29):3331-41.
5. Porte R, Fougeron D, Muñoz-Wolf N, Tabareau J, Georgel AF, Wallet F, Paget C, Trottein F, Chabalgoity JA, Carnoy C, Sirard JC. A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections. Antimicrob Agents Chemother. 2015;59(10):6064-72
6. Van Maele L, Carnoy C, Cayet D, Ivanov S, Porte R, Deruy E, Chabalgoity JA, Renauld JC, Eberl G, Benecke AG, Trottein F, Faveeuw C, Sirard JC. Activation of Type 3 innate lymphoid cells and interleukin 22 secretion in the lungs during Streptococcus pneumoniae infection. J Infect Dis. 2014;210(3):493-503
7. Van Maele L, Fougeron D, Janot L, Didierlaurent A, Cayet D, Tabareau J, Rumbo M, Corvo-Chamaillard S, Boulenouar S, Jeffs S, Vande Walle L, Lamkanfi M, Lemoine Y, Erard F, Hot D, Hussell T, Ryffel B, Benecke AG, Sirard JC. Airway structural cells regulate TLR5-mediated mucosal adjuvant activity. Mucosal Immunol. 2014;7(3):489-500
8. Muñoz N, Van Maele L, Marqués JM, Rial A, Sirard JC, Chabalgoity JA. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infect Immun. 2010;78(10):4226-33
9. Van Maele L, Carnoy C, Cayet D, Songhet P, Dumoutier L, Ferrero I, Janot L, Erard F, Bertout J, Leger H, Sebbane F, Benecke A, Renauld JC, Hardt WD, Ryffel B, Sirard JC. TLR5 signaling stimulates the innate production of IL-17 and IL-22 by CD3(neg)CD127+ immune cells in spleen and mucosa. J Immunol. 2010;185(2):1177-85

Patents

1. Novel immunoadjuvant flagellin-based compounds and use thereof. WO2009156405 - Inventors: Sirard JC
2. Methods and pharmaceutical compositions for the treatment of respiratory tract infections. WO2011161491 - Inventors: Sirard JC and Chabalgoity JA.
3. Methods and pharmaceutical compositions for the treatment of bacterial infections. WO2015011254 - Inventors: Hardt W, Chabalgoity J, Carnoy C, Kaiser P, Fougeron D, Munoz N, and Sirard JC.
4. Methods and pharmaceutical compositions for the treatment of bacterial superinfections post-influenza. WO2016102536. Inventors: Porte R, Trottein F, Carnoy C, and Sirard JC.

Scientific summary

Innate immune responses in bacterial pneumonia

Respiratory tract infections in general and pneumonia in particular currently represent the third leading cause of death worldwide. Bacterial pneumonia (either community- or hospital-acquired) is a leading cause of morbidity, quality-adjusted life year loss, and mortality in children, adults, and the elderly. Although antibiotics have transformed the management and treatment, their effectiveness is declining - because of antimicrobial resistance (AMR). The WHO estimates that bacterial infections due to AMR will outcompete any cause of death by 2050, meaning that it is crucial to develop new strategies to improve antibacterial treatment. In 2017, the WHO defined a priority list of bacteria for which new antibacterial therapies are urgently needed; it includes the major pneumonia-causing pathogens Pseudomonas aeruginosa, Klebsiella pneumoniae, and Streptococcus pneumoniae.

Targeting the innate immune system is an underexploited area of drug discovery for infectious diseases. Toll-like receptors (TLR) play a key role in sensing microorganisms and in regulating host innate immune defenses against pathogenic bacteria. Deciphering the mode of action of TLR following respiratory administration of TLR agonist is a major issue to tackle pneumonia. Flagellin, a protein component of many motile bacterial pathogens, signals through TLR5 is a promising biologic to circumvent pneumonia.

Antibiotics are considered as direct antimicrobial agents. However, there are several pieces of evidence that host innate immunity contributes to the efficacy of the antibiotic treatment. Thus, antibiotics by reducing the amount of the pathogenic bacteria, by modifying their virulence factors, and by killing/inactivating bacteria likely regulate the antibacterial immune responses.

Two main research axes covering basic research to clinical research are conducted:

• Development of inhaled flagellin as an adjunct therapy in bacterial pneumonia
• Identification of immune correlates of protection in the context of antibiotic treatment of pneumonia