Pet serine protease from enteroaggregative Escherichia coli stimulates the inflammatory response activating human macrophages

Abstract

Background: Pet is a toxin from the family of Serine Protease Autotransporters of Enterobacteriaceae which was initially identified in Enteroaggregative Escherichia coli strains. This protease exhibits enterotoxin properties, damages the cell cytoskeleton and induces intestinal epithelium alterations, which are associated with a severe inflammatory process. An in-vitro study was conducted to evaluate the effect of Pet on the migration of human peripheral blood monocytes-derived macrophages and its participation in the activation of the early inflammatory response and cytokine expression. Results: In the macrophage migration activation assay, Pet produced a similar effect to that induced by opsonized zymosan (ZAS). Regarding the cytokine expression, an increase of IL-8, TNF-α (pro-inflammatory) and IL-10 (anti-inflammatory) was identified. In addition to the above results, the nuclear translocation of NF-kB pp65 was also identified. These events are probably related to the inflammatory response identified in the histological examination of intestine rat samples inoculated with Pet during a ligated loop assay. Conclusion: The results showed that Pet participates as an immunostimulant molecule for macrophages, which activates both their mobility and cytokine expression. These observations suggest that the toxin participates in the inflammatory process that is observed during the host infection by EAEC Pet producing.