Régulation de la fonction anti-microbienne des macrophages aux infections pulmonaires

 

Maziar Divangahi

Institut de recherche du Centre universitaire de santé McGill

 

Domaine : maladies infectieuses et immunitaires

Programme chercheurs-boursiers - Junior 2

Concours 2015-2016

Globally, respiratory infections cause more than 4 million deaths per year, with influenza and tuberculosis (TB) in particular being major causes of mortality and morbidity in which present new challenges to clinicians who are left with no available therapeutic interventions.

The lung is the only organ that is constantly and directly exposed to the environment, while we are breathing 7-8 liters of air per minute. Thus, pulmonary immune responses must be tightly regulated to effectively eliminate invading microorganisms that reach the distal airways while minimizing immunopathology. Alveolar macrophages (AM) patrolling the airways are the first immune leukocytes to encounter the majority of pulmonary pathogens and their initial response to infection is critical to "set the tone" and orchestrate an effective immune response. The production of eicosanoids is a central determinant mediating the switch from homeostatic to anti-microbial function in macrophages. Thus, it is not surprising that many pathogens have evolved different strategies that target AM and allow them to evade both innate and adaptive immunity.

Therefore, harnessing the biological properties of macrophages by novel immunomodulatory methods (e.g., targeting eicosanoids or using nanoparticles) will allow for improved diagnostic, preventative, and therapeutic strategies for TB and influenza. In demonstrating that eicosanoids play a critical role in both influenza and TB infection, we hope that we are paving the way for clinical investigations into drugs that are already exist to target eicosanoids pathways.