Opportunistic Infections, Immunity, Environment and Lung Diseases
INSERM U1019 – CNRS UMR9017 – Lille University – CHU Lille – Institut Pasteur de Lille
Chronic respiratory diseases including COPD, asthma and cystic fibrosis are associated with opportunistic bacterial, viral and/or fungal infections. These infections favor the development of the disease and strongly accelerate disease progression. Recent data underlines that inflammatory disorders such as COPD arise from a dysregulation of immune responses related with altered microbiota-derived and environmental factors. Since environmental factors may alter the host response as well as the composition and the quality of microbiota, our overall aim is to understand how environmental factors (air pollutants, drug treatments, unhealthy diet) can facilitate lung infections in patients suffering from chronic pulmonary diseases. Specifically, we are focusing on their impact on host immune response, pathogen virulence (particularly pseudomonas aeruginosa) and microbiota as well as the outcomes on chronic or acute lung infections. Our research underlies on original experimental and cellular models and their validation through clinical studies. These data allow to propose new therapeutic approaches limiting the progression of chronic respiratory diseases.
- Muriel Pichavant, Emilie Fréalle, Eric Kipnis, Rodrigue Dessein, Philippe Gosset : The new team OpInfIELD gathers complementary expertises in immunity, environment, microbiology and lung diseases (chronic inflammatory and infectious diseases). This association allows to develop integrative approaches concerning our research area. This leads to identify new mechanisms responsible for the susceptibility to infection in the context of COPD (patent EP14306868), of pediatric asthma (Lejeune S et al) or following treatment with antibiotic (Dessein R et al). This knowledge allows to propose new therapies for acute exacerbation of COPD (Kone B. et al; Patent EP19306068) or for chronic infection by Pseudomonas aeruginosa, frequent in patients with cystic fibrosis (Project Glycocluster).
- Muriel Pichavant, Philippe Gosset : The development of an experimental model associating exposure to cigarette smoke and high fat diet allows to analyze the physiopathology of comorbidities related to this regimen (cardiovascular, metabolic, intestinal and unfertility-related diseases) (Duboy-Deruy E et al). Our present research aims to define the involvement of oxidative stress (Project CPER Commonly) and on IL-20 cytokines, key players in the interaction between mucosal immune response and microbiota (Projet ANR TheraSCUD). This preclinical model is also useful to measure the interest of therapies targeting the microbiota or the oxidative stress against these comorbidities.
- Layal Massara, Philippe Gosset : COPD is a multifactorial disease including genetic factors, as shown for the defect of α1-anti-trypsin. Some genetic polymorphisms of nicotinic receptors (an essential component of smoking dependance) are associated with COPD and cancer in smokers. In collaboration with Dr U. Maskos (Pasteur Institute of Paris) and Pr G. Deslée (INSERM UMS1250, Reims), we have shown that the interaction between a genetic polymorphism in a α5nicotinic receptor and an oxidative stress induces COPD-related lung lesions (submitted). These data were used to develop a project aiming to determine the role of this polymorphism (very frequent in the population) during COPD and their exacerbations (Project PINAChRAECOPD).
- Odile Poulain, Corine Glineur, Karine Faure : Our expertise in immunology and respiratory infectious diseases prompted us to develop projects on COVID-19. Our projects aimed to better understand the physiopathology of severe form of this disease in the Licorne cohort of COVID19 patients (CHU of Lille) (ANR project CritiSARS2). Moreover, smoking and COPD impact the infection and the development of the disease. In order to define these interactions, we evaluate the role of nicotinic receptors both during the early step of the infection and the inflammatory reaction associated with the COVID19 (ANR project NirCOVID).
COPDAir (Dr O. Le Rouzic, CHU Lille)
To better understand the role of air environment during acute exacerbation of COPD and its impact on airway microbiota and local immune response.
Virasthma2 (Dr A. Deschildre, CHU Lille)
To identify the role of viral infections and of the alterations of the immune response during the development of pediatric asthma in prescholar children and their followup until adulthood.
Lejeune S, Pichavant M, Engelmann I, Béghin L, Drumez E, Le Rouzic O, Dessein R, Rogeau S, Beke T, Kervoaze G, Delvart C, Ducoin H, Pouessel G, Le Mée A, Boileau S, Roussel J, Bonnel C, Mordacq C, Thumerelle C, Gosset P, Deschildre A.
Severe preschool asthmatics have altered cytokine and anti-viral responses during exacerbation.
Pediatr Allergy Immunol. 2020 Aug;31(6):651-661. doi: 10.1111/pai.13268. Epub 2020 May 17. PubMed [citation] PMID: 32352598
Koné B, Pérez-Cruz M, Porte R, Hennegrave F, Carnoy C, Gosset P, Trottein F, Sirard JC, Pichavant M, Gosset P.
Boosting the IL-22 response using flagellin prevents bacterial infection in cigarette smoke-exposed mice.
Clin Exp Immunol. 2020 Aug;201(2):171-186. doi: 10.1111/cei.13445. Epub 2020 May 17. PubMed [citation] PMID: 32324274, PMCID: PMC7366752
Dessein R, Bauduin M, Grandjean T, Le Guern R, Figeac M, Beury D, Faure K, Faveeuw C, Guery B, Gosset P, Kipnis E.
Antibiotic-related gut dysbiosis induces lung immunodepression and worsens lung infection in mice.
Crit Care. 2020 Oct 15;24(1):611. doi: 10.1186/s13054-020-03320-8. PubMed [citation] PMID: 33076936, PMCID: PMC7574210
Rémy G, Dubois-Deruy E, Alard J, Kervoaze G, Chwastyniak M, Baron M, Beury D, Siegwald L, Caboche S, Hot D, Gosset P, Grangette C, Pinet F, Wolowczuk I, Pichavant M.
Modelling the Impact of Chronic Cigarette Smoke Exposure in Obese Mice: Metabolic, Pulmonary, Intestinal, and Cardiac Issues.
Nutrients. 2020 Mar 20;12(3):827. doi: 10.3390/nu12030827
Gosset P, Pichavant M, Le Roux M, Robert B, Martineau P, Chentouf M.
Antibodies specific for IL-20Rb and uses thereof for the treatment of acute exacerbation of chronic obstructive pulmonary disease.
Patent EP19306068 (Septembre 2020)
COPD ; Asthma ; Cystic fibrosis ; Cytokines ; Pseudomonas aeruginosa ; Virus ; Antigen-presenting cells ; Infection ; Lung ; Microbiota ; Pollution