Jean-Claude Sirard
  • E-mail :[email]
  • Phone : +33 3 20 87 73 19
  • Location : Lille, France
Last update 2017-06-21 14:04:50.862

Jean-Claude Sirard PhD Microbiology

Course and current status

Current position

  • Project 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 deLille

  • 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”

Significant publications

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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. EP14307154.6, 23/12/2014. Inventors: Porte R, Trottein F, Carnoy C, and Sirard JC.

Scientific summary

Innate and adaptive immune responses to TLR5 adjuvants and bacterial infections

Toll-like receptors (TLR) play a key role in sensing microorganisms and in regulating host immune responses. Deciphering the mode of action of TLR following mucosal administration of TLR agonist, especially in the respiratory tract, is a major issue. Flagellin, a component of many bacterial pathogens that acts through TLR5 (and NAIP5-6/NLRC4) was used in these studies. Our recent findings indicate a key role of airway epithelium in the induction of host immunity following mucosal delivery of flagellin (Van Maele, 2014). The current objective is to dissect the interplay mechanisms between airway epithelium and dendritic cells (DCs) in pulmonary immunity in order to develop new vaccination strategies.

In addition, the impact of compartmentalization of TLR5 signaling on innate defenses was investigated. respiratory delivery is associated with epithelial signaling and the recruitment of neutrophils that promote antimicrobial defenses (Munoz, 2010; Porte, 2015). In contrast, systemic delivery of flagellin stimulates the early mucosal production of IL-17 and IL-22, known to play crucial roles in antimicrobial defense by type 3 innate lymphoid cells or ILC3 (Van Maele, 2010; Van Maele, 2014). Using Streptococcus pneumoniae that is the main cause of bacterial pneumonia, meningitis and septicaemia in humans, protection against respiratory infection was induced by flagellin delivered either locally or in the systemic compartment.  Our objective is to further analyze the mechanisms involved in the recruitment and activation of mucosal epithelium, neutrophils and ILC3 that can be manipulated for the treatment of respiratory infections.

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