Induction of neutrophil extracellular traps (NETs) by Campylobacter jejuni.

Campylobacter jejuni is the leading cause of bacterial-derived gastroenteritis worldwide and can lead to several post-infectious inflammatory disorders. Despite the prevalence and health impacts of the bacterium, interactions between the host innate immune system and C. jejuni remain poorly understood. To expand on earlier work demonstrating that neutrophils traffic to the site of infection in an animal model of campylobacteriosis, we identified significant increases in several predominantly neutrophil-derived proteins in the feces of C. jejuni-infected patients, including lipocalin-2, myeloperoxidase, and neutrophil elastase. In addition to demonstrating that these proteins significantly inhibited C. jejuni growth, we determined they are released during formation of C. jejuni-induced neutrophil extracellular traps (NETs). Using quantitative and qualitative methods, we found that purified human neutrophils are activated by C. jejuni and exhibit signatures of NET generation, including presence of protein arginine deiminase-4, histone citrullination, myeloperoxidase, neutrophil elastase release, and DNA extrusion. Production of NETs correlated with C. jejuni phagocytosis/endocytosis and invasion of neutrophils, suggesting that host- and bacterial-mediated activities are responsible for NET induction. Further, NET-like structures were observed within intestinal tissue of C. jejuni infected ferrets. Lastly, induction of NETs significantly increased human colonocyte cytotoxicity, indicating that NET formation during C. jejuni infection may contribute to observed tissue pathology. These findings provide further understanding of C. jejuni-neutrophil interactions and inflammatory responses during campylobacteriosis. This article is protected by copyright. All rights reserved.