ABSTRACT
The human pathogen Mycobacterium tuberculosis (Mtb) produces a lipoglycan, namely mannose-capped lipoarabinomannan, which displays anti-inflammatory properties by targeting specific C-type lectin receptors on the surface of immune cells. Designed and synthesized poly(phosphorhydrazone) dendrimers grafted with mannose residues, called mannodendrimers, to mimic the bioactive supramolecular structure of mannose-capped lipoarabinomannan, with the objective of developing innovative anti-inflammatory molecules. By mimicking the strategy used by Mtb to down-regulate the host inflammatory response which is a novel type of fully synthetic powerful anti-inflammatory molecule. To test the anti-inflammatory activity of mannodendrimers in vivo, used a model of acute lung inflammation, which involved exposure of mice to aerosolized lipopolysaccharide. Neutrophil sequestration into the lungs and associated inflammatory damage are believed to contribute to the pathogenesis of diverse lung diseases, including acute lung injury, the acute respiratory distress syndrome, chronic obstructive lung disease, and cystic fibrosis.
