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<p> The cellular, molecular, and genetic mechanisms underlying the pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) are not well understood. The purpose of this thesis was to address the hypothesis that microbial infection is important for the development and/or progression of COPD through investigation of how cigarette smoke alters the response to a bacterial challenge in a mouse model of cigarette smoke-exposure. To this end, in chapter 2 of this thesis we tested the hypothesis that cigarette smoke-exposure attenuates the ability of alveolar macrophages to sense microbial antigens through innate pattern recognition receptors. The central point of this study was the observation that alveolar macrophages isolated from cigarette smoke-exposed mice had attenuated expression of typical inflammatory cytokines following microbial stimulation. Building on this main observation, in chapter 3 we questioned what the consequences of this would be to an in vivo bacterial challenge with nontypeable Haemophilus influenzae. We demonstrated that cigarette smoke-exposure resulted in chronic inflammation, this inflammation was exacerbated following bacterial challenge, and perhaps most importantly, the nature of the inflammatory response was altered. Interestingly, an observation from the study in chapter 3 indicated that exacerbated inflammation in cigarette smoke-exposed mice may be beneficial for clearance of the bacteria, but may come at the expense of damage to the lungs. Consequently, in chapter 4 we questioned the strain and dose/ frequency stringencies of cigarette smoke-exposure on the observation of accelerated bacterial clearance. We demonstrated a role for antibodies in bacterial clearance. Collectively, this thesis provides insight into our understanding of COPD by demonstrating that cigarette smoke-exposure alters the pulmonary immune/ inflammatory response to a microbial challenge, which has a detrimental impact on the lungs. </p> / Thesis / Doctor of Philosophy (PhD)

La gestion de l'infection endodontique est la clé de la réussite de tout traitement endodontique. La reproduction in vitro du biofilm endocanalaire sauvage, qui se compose d'environ 500 espèces bactériennes différentes est à ce jour impossible. Cependant, tester un protocole de désinfection dans des conditions de laboratoire et ce avant toute application clinique reste indispensable. Il ressort que le développement d'un modèle qui ressemblerait structurellement à son type homologue sauvage se montre crucial. Dans le laboratoire MICORALIS (EA 7354) nous nous sommes intéressés à la conception et à la réalisation d'un biofilm polybactérien artificiel. La recherche bibliographique a permis de sélectionner S. salivarius, E. faecalis, F. nucleatum et P. gingivalis qui sont des représentants de différents groupes colonisateurs de l’espace endodontique et qui coexistent. Après une série d'analyse au MEB puis des examens à l'aide de la technique FISH-confocale (sondes ARNr 16S), nous avons pu démontrer que ces bactéries sont présentes dans la composition d’un biofilm mature après 21 jours sur la dentine péricanalaire. Ces investigations nous ont permis de géo-localiser des bactéries dans les tubuli dentinaires jusqu’à 500µm et parmi elles, P. gingivalis était statistiquement prédominante. Afin de répondre aux exigences des objectifs de notre étude, six groupes de 12 échantillons contaminés par le biofilm expérimental ont servi à tester 6 techniques de décontamination endodontique / Management of infection is the key to a successful root canal treatment and development of a study model of endodontic biofilm which resemble structurally to its wild type counterpart seems crucial before any clinical application of different protocols. However, the in vitro reproduction of the root canal biofilm which consists of about 500 different bacterial species is very difficult. In laboratory MICORALIS (EA 7354) we were interested in conception of an artificial polybacterial. The bibliographical research allowed to choose S. salivarius, E. faecalis, F. nucleatum and P. gingivalis which are representatives of different groups of root canal biofilm colonizers. Following a series of periodic Scanning Electron Microscopies of samples and furthermore by help of FISH-Confocal imaging of 16S rRNA, we could prove the presence of these bacteria inside the biofilm structure and illustrate their distribution over the root canal system. In addition, it was possible also to confirm the maturation time needed to obtain the biofilm model, which is resistant enough to be used in vitro for endodontic disinfection investigation. After being characterized, we treated the model biofilm with different endodontic decontamination protocols