The respiratory barrier, from commensalism to pathogenicity, the search for new paradigms

The sixth and final lecture of the academic year was entitled "The respiratory barrier, from commensalism to pathogenicity, the search for new paradigms". This lecture detailed the complexity of the respiratory tree in terms of its interface with the microbial world. It is an open space, marked by the presence of abundant commensal flora in its upper part, particularly in the rhinopharynx, followed by a lower respiratory tract (trachea, bronchi and alveoli) generally considered sterile. This sterility is relative, however, and can be described as "dynamic sterility", ensured by a complex tracheobronchial epithelial mechanism combining the production of microorganism-trapping mucus and its retrograde mobilization by ciliated cells, which ensure the continuous evacuation of microorganisms and contaminating particles. The pulmonary alveolus has its own protection system, thanks to the permanent presence of alveolar macrophages and the rapid recruitment of inflammatory cells such as neutrophils in the event of aggression. On these now well-established foundations, we examined the mechanisms of subversion of this eminently fragile barrier by pathogenic bacteria and viruses. Two model microorganisms were mainly considered: S. Pneumoniae (pneumococcus) and influenza virus. An important part of the lecture was dedicated to understanding the "commensal-pathogenic" concept illustrated by S. Pneumoniae , and to identifying the mechanisms that enable this transition. The role of a viral infection prior to the spread of S. Pneumoniae was developed, based on evidence of a "preparatory" role of influenza in the spread of pneumococcal infection. The mechanisms of this "preparation" have been envisaged, ranging from altered immune response profiles to altered epithelial repair mechanisms facilitating pneumococcal translocation across the respiratory barrier and/or colonization into the alveolar spaces. It is likely that the vast majority of deaths observed during the Spanish influenza epidemic of 1918 were linked to pulmonary and systemic pneumococcal superinfection.