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

• Published in: Infection and immunity 2018-06, Vol.86 (6)
• Main Authors: Shank, Janette M, Kelley, Brittni R, Jackson, Joseph W, Tweedie, Jessica L, Franklin, Dana, Damo, Steven M, Gaddy, Jennifer A, Murphy, Caitlin N, Johnson, Jeremiah G
• Format: Article
• Language: English
• Subjects: Animals; Campylobacter jejuni - drug effects; Campylobacter jejuni - growth & development; Colon - cytology; Colon - microbiology; Female; Ferrets; Host Response and Inflammation; Humans; Leukocytes; Male; Microbial Sensitivity Tests; S100A12 Protein - genetics; S100A12 Protein - metabolism; Zinc - metabolism
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.00234-18

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.