Le monde
de l'infiniment petit

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Team Bacteria, Antibiotics, and Immunity

Respiratory tract infections represent the third major cause of death worldwide. Among them, bacterial pneumonia (either community- or hospital-acquired) are major causes of morbidity, quality-adjusted life year loss, and mortality in children, adults, and the elderly. Although the discovery of antibiotics to treat bacterial pneumonia was a remarkable achievement in the 20th century, the effectiveness of antibiotics is declining, because of antimicrobial resistance (AMR). The World Health Organization (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.

 

The team "Bacteria, Antibiotics, and Immunity" studies pathogenic bacteria responsible for pneumonia listed by the WHO as priority targets in the fight against AMR: Streptococcus pneumoniae and Klebsiella pneumoniae. Our studies make use of cell and animal models as well as clinical studies with the GHICL hospitals in Lille to translate findings from bench to bedside. The team especially investigates the immune responses that are triggered by the bacterial infection of the respiratory tract, by the antibiotics during the treatment of such infections and aims to define groundbreaking interventions that increase innate immune defenses. Notably, innate immunity mobilizeq a variety of antibacterial effectors; Emergence of resistance to these immune effectors would be unlikely. The ultimate objective of the team is to combat the emergence of AMR by novel interventions that combine stimulation of innate immune responses and antibiotherapy.

The team currently explore three research axes:

  • Demonstrating the proof-of-concept of aerosol delivery of immune-modulator as an innovative pneumonia treatment
  • Defining the contribution of innate immune effectors in the effectiveness of antibiotic treatment of infections
  • Dissecting the mechanisms involved in the innate IL-17/IL-22 responses to develop immune-boosters of antibiotics

In conclusion, our studies tests and optimizes emerging concepts of immunotherapy of bacterial pneumonia in combination with the standard of care that are antibiotics in order to address the problem of AMR.

Pour plus de détails sur l'équipe : ICI

 

Demonstrate the proof of concept of aerosol delivery of immune-modulator
as an innovative
pneumonia treatment

The team coordinates the European project FAIR (https://fair-flagellin.eu) that aims at targeting the innate immune system as an underexploited area of drug discovery for infectious diseases. To this purpose, the FAIR project develops inhaled flagellin as an adjunct therapy in bacterial pneumonia. Flagellin is an agonist of the Toll-like receptor 5 that activates signaling in the respiratory epithelium and thus, protective innate defenses against pneumonia. It has already been shown that flagellin activates local or systemic innate immunity and enhances the therapeutic outcome of pneumonia caused by antibiotic susceptible or resistant S. pneumoniae and K. pneumoniae. We aim at dissecting the mode of action of flagellin during pneumonia treatment. The project also ambitions to setup a first-in-man phase I clinical trial.

Decipher the nature of innate immune effectors contributing to antibiotics efficacy during bacterial pneumonia

Antibiotics are uniquely considered as direct antimicrobial agents, and most efficacy evaluations are based on in vitro assays or immunosuppressed animals. Growing evidence suggests that antibioticsinteract with host innate immunity to provide potent indirect effects which enhance bacterial clearance and may result in more rapid and complete therapeutic effects. The team is characterizing the dynamics of myeloid cell differentiation and functions during the antibiotic treatment of bacterialinfection in mice, in order to identify novel immunomodulatory agents.

Dissect the innate IL-17/IL-22 responses to improve treatment of pneumonia and boost antibiotic effectiveness.

The innate lymphocytes that produce the cytokines IL-17 and IL-22 are essential to promote respiratory innate antimicrobial defenses and tissue repair. The team aims at understanding how these responses are induced in the respiratory tract during self-limiting bacterial pneumonia in order to develop innovative interventions.

Our new Post doc
Our new PhD students

Mara Baldry - Postdoctoral researcher Scientific manager of FAIR. Immune corelates of protection to inhaled flagellin as adjunct of antibiotics.

Charlotte Costa - PhD Student. Impact of immunotherapies on the treatment and emergence of antibiotic-resistant pneumonia.

Mélanie Mondemé - PhD Student. Dynamics of myeloid cells during antibiotherapy of pneumonia.

Xing Li - PhD Student. Innate response of human primary respiratory cells to infections and immune-modulators.

Yasmine Zeroual - PhD Student. Modeling of protective innate immunity by Omics analysis.


Titre du document Équipes précédemment présentées

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SARS-CoV-2 infection in nonhuman primates alters the composition and functional activity of the gut microbiota.
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The UPR sensor IRE1α promotes dendritic cell responses to control Toxoplasmagondii infection
Anaïs F Poncet, Victor Bosteels, Eik Hoffmann, Sylia Chehade, Sofie Rennen, Ludovic Huot, Véronique Peucelle, Sandra Maréchal, Jamal Khalife, Nicolas Blanchard, Sophie Janssens, Sabrina Marion.
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TgAP2IX-5 is a key transcriptional regulator of the asexual cell cycle division in Toxoplasma gondii.
Asma S. Khelifa, Cecilia Guillen Sanchez, Kevin M. Lesage, Ludovic Huot, Thomas Mouveaux, Pierre Pericard, Nicolas Barois, Helene Touzet, Guillemette Marot, Emmanuel Roger et Mathieu Gissot.
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Plasmodium yoelii Uses a TLR3-Dependent Pathway to Achieve Mammalian Host Parasitism
Keswani T, Delcroix-Genete D, Herbert F, Leleu I, Lambert C, Draheim M, Salome-Desnoulez S, Saliou JM, Cazenave PA, Silvie O, Roland J, Pied S. (2020)

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