Proteoglycofili are glycosaminoglycan-containing fibrillar components released by neutrophils to neutralize bacteria
Here we uncover that neutrophils release a previously unidentified fibrillar complex, named proteoglycofili (PGF) under hypoxic conditions or upon bacterial infection, using Shigella as a model. PGF are preferentially released by neutrophils over NETs upon bacterial infection. We demonstrated that PGF are released by living neutrophils, do not contain DNA and are mainly composed of granule proteins. We revealed that the fibrillar structure of PGF is sustained by two glycosaminoglycans (GAGs), hyaluronic acid and chondroitin sulfate, firstly identified here to be released by neutrophils. We demonstrated that PGF are potent antimicrobials, which degrade virulence factors of Shigella and block its growth, similarly with E. coli or Salmonella. We confirmed that GAGs were essential for PGF antimicrobial activity in vitro and in vivo. Beyond bacterial infections, our results strongly suggest that GAGs may be released by neutrophils in a broad range of inflammatory diseases to be further explored. Overall design: RNA-seq was performed at T0 (neutrophils freshly purified) and HG (neutrophils incubated for 18h at 37°C under anoxic conditions). Four replicates were generated for each condition.