The Host Antimicrobial Protein Calgranulin C Participates in the Control of Campylobacter jejuni Growth via Zinc Sequestration

Abstract

is a leading cause of bacterially derived gastroenteritis worldwide. is most commonly acquired through the consumption of undercooked poultry meat or through drinking contaminated water. Following ingestion, adheres to the intestinal epithelium and mucus layer, causing toxin-mediated inflammation and inhibition of fluid reabsorption. Currently, the human response to infection is relatively unknown, and animal hosts that model these responses are rare. As such, we examined patient fecal samples for the accumulation of the neutrophil protein calgranulin C during infection with In response to infection, calgranulin C was significantly increased in the feces of humans. To determine whether calgranulin C accumulation occurs in an animal model, we examined disease in ferrets. Ferrets were effectively infected by, with peak fecal loads observed at day 3 postinfection and full resolution by day 12. Serum levels of interleukin-10 (IL-10) and tumor necrosis factor alpha (TNF-α) significantly increased in response to infection, which resulted in leukocyte trafficking to the colon. As a result, calgranulin C increased in the feces of ferrets at the time when loads decreased. Further, the addition of purified calgranulin C to cultures was found to inhibit growth in a zinc-dependent manner. These results suggest that upon infection with , leukocytes trafficked to the intestine release calgranulin C as a mechanism for inhibiting growth.

RNA-based thermoregulation of a Campylobacter jejuni zinc resistance determinant

“…jejuni infected patients, is known to inhibit C . jejuni growth [ 48 ]. Yet, using a recently developed mouse model of C .…”

Campylobacter jejuni induces differentiation of human neutrophils to the CD16hi/CD62Llo subtype which possess cancer promoting activities

“…For example, the decreased apoptosis of neutrophil populations we observed during infection likely leads to prolonged exposure of the surrounding gastrointestinal tissues to the activities of neutrophils [1, 57]. This includes several processes and products we previously examined that may directly damage host cells or are exceedingly proinflammatory, including the release of S100A12, lipocalin-2, myeloperoxidase, and neutrophil elastase [25, 49]. Beyond these more classical responses, our current work suggests that a portion of the neutrophil population may be inappropriately immunosuppressive and counteract specific components of adaptive immunity (e.g., T cells).…”

“…Beyond this, there are several similarities that exist between what has been found during infection with H. pylori and C. jejuni . For example, both H. pylori and C. jejuni infection result in high levels of neutrophil recruitment and activity, which result in severe inflammation at the site of infection [24,25,26]. Importantly, the chronic neutrophilic response to H. pylori infection is believed to result from immune dysregulation and has been suggested to contribute to the development of gastric cancer [27].…”

A porcine ligated loop model reveals new insight into the host immune response againstCampylobacter jejuni

“…This trend has been observed in human infections where elevated levels of the neutrophil proteins S100A8, S100A9, and S100A12 are detectible in the stool. 61 The S100A8 and S100A9 proteins are antimicrobial factors and potent neutrophil chemoattractants; 30,62 these proteins also promote neutrophil activation, and S100A9 potentiates IL-8 production from neutrophils in response to other stimuli. 63 In addition to these three proteins, our study has uncovered additional host factors that appear in the intestine during C. jejuni infection, including antimicrobial neutrophil related proteins.…”