Induction of neutrophil extracellular traps by Campylobacter jejuni
- 20 May 2020
- journal article
- research article
- Published by Hindawi Limited in Cellular Microbiology
- Vol. 22 (8), e13210
- https://doi.org/10.1111/cmi.13210
Abstract
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 faeces 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. Finally, 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.Keywords
Funding Information
- National Center for Research Resources (UL1 RR024975‐01, UL1 TR000445‐06)
- National Institutes of Health (CA68485, DK20593, DK58404, DK59637, EY08126, K08 Al151100, P30 DK058404, R01 AI134036, R01 HD090061, U01TR002398)
- U.S. Department of Veterans Affairs (IK2BX001701)
- University of Tennessee (Start Up Fund)
- Vanderbilt University Medical Center (Faculty Research Scholars Award)
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