Opportunistic Infection Immunity Environment & Lung Diseases


Team Leader:

Philippe GOSSET

Contact

Dr. P. Gosset is a senior scientist (INSERM CRHC) and he was a group leader (before the upcoming of OpInfIELD) in the team "Lung Infection and Innate Immunity" (LI3) at the CIIL. Dr. P. Gosset is coauthor of more than 135 papers referenced in PubMed (H-index= 45). Before to work on lung infection in chronic inflammatory diseases (COPD and asthma) using complementary approaches (from bench to bedside), he has work on the analysis of the immune and inflammatory reaction during Asthma and COPD and the response to lung cells to environmental factors. This is related to strong expertise in immunology (both in the clinic and in the murine model) but also on lung cells. Our research implicates strong interactions with clinicians as well as the development of a murine model of bacteria-induced COPD exacerbation. Our recent data had allowed to deposit 6 patents and to presently propose a new therapeutic approach for AE-COPD. Moreover, we have developed an up-to-date platform in order to measure the respiratory function in mice.

 

The "OpInfIELD" team was created by merging the "Respiratory Infections and Inflammatory diseases" group (Dr P. Gosset) of the former "Lung Infection and Innate Immunity" team (LI3, CIIL) and "Host Pathogen Translational Research" team (Pr E. Kipnis, EA 7366, Univ. Lille). To benefit from interactions with clinical and microbiology departments, this team is located on two sites: the Lille University Medical School Research Center on the Lille University Teaching Hospital Campus (Pôle recherche Faculté de Médecine de Lille) and the Pasteur Institute of Lille. Most of the chronic respiratory diseases, namely COPD (the fourth cause of death worldwide), asthma and cystic fibrosis (CF, the most frequent genetic disease) are associated with opportunistic bacterial, viral and/or fungal infections. These infections by streptococcus pneumonia, haemophilus influenza (COPD) and pseudomonas aeruginosa (Cystic fibrosis) favor the development of the disease but also markedly amplify lung inflammation, resulting in tissue damage and disease progression. These bacterial as well as viral infections are also very frequent in newborn leading to bronchopathies which can progress towards severe forms of asthma or juvenile forms of COPD.

This process is also associated with the development of comorbidities including cardiovascular, metabolic and intestinal disorders. These often recurrent infectious episodes called acute exacerbations (AE) trigger a vicious cycle ultimately leading to the patients' death. Many environmental factors play a key role in the physiopathology of underlying respiratory inflammatory diseases and/or in the susceptibility to infections. These factors include airway pollutants such as cigarette smoke (CS) and nutrition (particularly with high fat diet), but also frequently used therapeutics such as glucocorticoids and antibiotics. These are involved in increased susceptibility to infections and might lead to lung and gut dysbiosis in both COPD and CF patients. As in the gut, the airways also harbor microbial communities or microbiota, even in healthy subjects. The development and the homeostasis of the immune system depend on its symbiotic relationship with microbiota. Recent data underlines that inflammatory disorders such as COPD arise from a dysregulation of immune responses against self, 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 can facilitate infections in patients suffering from chronic pulmonary diseases. Our research is presently focused on the impact of environmental factors on the host immune response and the microbiota and the outcomes on responses to chronic or acute lung infections. More specifically, we will focus our research on the alteration of the mucosal innate immune response and of the lung and gut microbiota (including colonizing and/or infecting pathogens such as Pseudomonas aeruginosa) and their implication in disease progression. To these ends, we have developed experimental models associating the effects of environmental factors such as smoking and bacterial infections on the lung immune response during COPD or in ΔF-508 CF-like mice.

The validation of experimentally generated paradigms will be sought through clinical studies. The identification of critical factors related to host immune response and/or composition and function(s) of the microbiota will allow us to propose new therapeutic approaches aiming at preventing and/or treating COPD exacerbations and P. aeruginosa infections during CF.