WS10.7 The role of C-type lectins in the recognition of Pseudomonas aeruginosa

Abstract

Colonization and persistent lung infection by Pseudomonas aeruginosa (PA), is an important cause of morbidity and mortality in Cystic Fibrosis patients. PA persists inside the lungs by forming drug-resistant biofilms. Biofilms are enclosed in extracellular polymeric substance (EPS) which functions as a sticky matrix that protects biofilms from harsh environment. Polysaccharide synthesis locus (psl) is an important mannose rich matrix component that promotes biofilm formation. Studies showed that psl reduces the phagocytic activity of immune cells and complement activation. Incubation of PA biofilms with labelled purified human monocytes and macrophages indicate that macrophages, unlike monocytes attached to PA biofilms. Cell surface receptors expressed by monocytes and macrophages were compared and, as previously described, high mannose receptor (MR) expression was found in macrophages. MR is a carbohydrate binding receptor that plays a crucial role in innate immunity. MR binds mannose-rich carbohydrates through C-type lectin-like domains (CTLD) 4 to 7. Using a recombinant protein containing the mannose binding region of MR (CTLD 4–7-Fc) it was found that MR can directly interact with PA biofilms and that this binding is increased when psl expression is increased. We hypothesize that MR expressed by macrophages and dendritic cells might contribute to PA recognition through psl. Future work will explore the capability of immune mammalian C-type lectins to recognise PA biofilms and purified psl and elucidate the role of psl in modulating the recognition of PA by immune cells using PA strains expressing different combinations of extracellular polysaccharides.