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Protein aggregation in wound fluid confines bacterial lipopolysaccharide and reduces inflammation

Petrlova, J.; Hartman, E.; Petruk, G.; Lim, J. C. H.; Adav, S. S.; Kjellstrom, S.; Puthia, M.; Schmidtchen, A.

2023-01-28 immunology
10.1101/2023.01.27.525825 bioRxiv
Show abstract

Bacterial lipopolysaccharide (LPS) induces the rapid formation of protein aggregates in human wound fluid. We aimed to define such LPS-induced aggregates and the functional consequences of protein aggregation using a combination of mass spectrometry analyses, biochemical imaging, and experimental animal models. We show that such wound-fluid aggregates contain a multitude of protein classes, including sequences from coagulation factors, annexins, histones, antimicrobial proteins/peptides, and apolipoproteins. Proteins and peptides with a high aggregation propensity were identified, and selected components were verified biochemically by western blot analysis. Staining by thioflavin T and the Amytracker probe demonstrated the presence of amyloid-like aggregates formed after exposure to LPS in vitro in human wound fluid and in vivo in porcine wound models. Using NF-{kappa}B-reporter mice and IVIS bioimaging, we show that such wound-fluid LPS aggregates induce a significant reduction in local inflammation compared with LPS in plasma. The results show that protein/peptide aggregation is a mechanism for confining LPS and reducing inflammation and further underscore the connection between host defense and amyloidogenesis.

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