Recognition of bacterial biofilms by innate immune cells

P.aeruginosa (PA) is emerging as major opportunistic pathogen of clinical relevance. Acute PA infection is particularly serious in patients suffering from ventilator-associated pneumonia and chemotherapy-associated neutropenia (1,2). PA also causes chronic infection in cystic fibrosis (CF) patients where the lack of effective mucocilliary clearance and intensive antibiotic treatment provides a unique niche for PA to persist leading to the generation of PA strains highly adapted to the CF lung (3). PA causes a resilient infection difficult to eradicate because of the intrinsic resistance of PA to antibiotics, its ability to produce a wide range of virulence factors including toxins, proteases and lipids and form biofilms (3). Biofilms represent a formidable adversary for innate immune cells responsible for bacterial clearance, macrophages and neutrophils and can lead to the induction of chronic inflammation (4). To better understand the ability of biofilms to modulate the inflammatory response, this project aims to study the interaction of PA biofilms with human innate immune cells. We will determine how immune cells influence biofilms by assessing biofilm development in the presence of immune cells and conversely, how biofilms modulate the activation of human macrophages and neutrophils by assessing cytokine production, cell survival (5) and formation of extracellular nets in biofilms-immune cells co-cultures.