Oxytetracycline reduces inflammation and treponeme burden whereas vitamin D3 promotes β-defensin expression in bovine infectious digital dermatitis
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Digital dermatitis (DD), a common ulcerative disease of the bovine foot causing lameness and reducing productivity and animal welfare, is associated with infection by spirochete Treponema bacteria. Topical tetracycline, the most common treatment, has inconsistent cure rates; therefore, new therapeutic options are needed. We compared effects of topical oxytetracycline and vitamin D3 on innate immunity in DD-affected skin. Cows with active DD lesions were treated topically with oxytetracycline or vitamin D3 and skin biopsies were collected from lesions. Tissue samples were examined histologically, transcriptional expression of pro-inflammatory cytokines, Toll-like receptors (TLRs), and host defense peptides assessed, and the presence of specific treponeme species determined. Effects of treatments at a mechanistic level were studied in a human keratinocyte model of treponeme infection. Oxytetracycline promoted hyperplastic scab formation in ulcerated DD lesions and decreased transcriptional expression of Cxcl-8 (neutrophil chemoattractant). Oxytetracycline also reduced numbers of Treponema phagedenis and T. pedis and enhanced Tlr2 mRNA expression. Vitamin D3 did not modify expression of cytokines or Tlrs, or bacterial loads, but enhanced transcription of tracheal antimicrobial peptide (Tap), a key bovine β-defensin. Combing oxytetracycline and vitamin D3 provides complementary clinical benefits in controlling DD through a combination of antimicrobial, immunomodulatory, and pro-healing activities.
KeywordsTreponema spp. Digital dermatitis Cattle Oxytetracycline Vitamin D3 Cathelicidins β-Defensins Interleukin 8
We thank certified hoof trimmers Rob Geier (Casper Trimming, Calgary, AB, Canada) and Elbert Koster (No-tilt Hoof Trimming, Calgary, AB, Canada) for facilitating collection of biopsies. We also thank Dr. Brielle Rosa for her critical review and editing the manuscript.
KW and EC conceived and designed the experiments. KW and KO conducted animal sampling. KW and PL conducted in vitro experiments and analyzed data. RA performed Treponema spp. identification by culture and qPCR. RA and PL conducted immunohistochemistry and CK conducted histopathological examination. KO, CK, RA, JDB, HB, and EC contributed to data analysis and interpretation as well as manuscript editing. KW, PL, CK, and EC drafted and wrote the manuscript.
This work was supported by the Natural Sciences and Engineering Research Council (NSERC) Discovery Grant (RGPAS-2017- 507827) and the Alberta Agriculture and Forestry (2019F040R) to ERC. KW was supported by Queen Elizabeth II Graduate Scholarship.
Compliance with ethical standards
The authors declare no conflicts of interest. Studies involving cattle were reviewed and approved by the University of Calgary Animal Care Guidelines (AC16-0070) for the care and use of animals. The owner’s written informed consent was obtained prior to the use of any cattle.
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