Exploration of innate immune response during infectious bovine digital dermatitis and the evaluation of topical therapeutic treatment

Digital dermatitis (DD) is a frequently occurring infectious disease amongst dairy cattle associated with ulcerative and necrotizing lesions. Due to the associated pain and lameness, DD is a recognized animal welfare problem and has economic implications associated with decreased milk production, lower reproduction rates, and premature culling. DD is of polymicrobial etiology, with the main causative agent identified as belonging to the Treponema genus. Current treatments include topical application of antibiotics such as oxytetracycline or foot baths containing caustic chemicals; however clinical cure rates remain highly variable. In this thesis cattle with DD were monitored to explore the skin innate immune response. An exhaustive description of the inflammatory response during disease progression and a novel description of bovine host defence peptides (HDPs) and their contribution to disease resolution are found herein. It was observed that active DD was characterized by necrotic tissue populated with neutrophils and elevated Cxcl-8 and Tlr4 expression. Tracheal antimicrobial peptide (Tap) was vastly increased in active lesions and key for the resolution of DD. An in vitro model utilizing human keratinocytes showed pro-inflammatory cytokines are released in the absence of living treponemes through Tlr2 signaling and that secretory treponeme products induced cathelicidins. The ability to manipulate inflammatory reactions via treatment with vitamin D3 in DD was compared to the commonly-used oxytetracycline. A cohort of cattle with M2 were topically treated with vitamin D3 against powdered oxytetracycline for 5 days. Although vitamin D3 did elevated Tap expression, lesions and inflammatory markers remained unchanged. In contrast, oxytetracycline reduced neutrophil chemoattractant Cxcl-8 while Tlr2 remained elevated. Histologic assessment evidenced scab formation. Taken together, this thesis established the skin innate response and role of host defence peptides (Tap) during DD and supported oxytetracycline as a treatment, providing lesion resolution and aiding in bacterial elimination.

Name thesis:degree_name

Master of Science (MSc)

Grantor dc:publisher.institution

Graduate Studies

Year dc:date.issued

2018

Author dc:creator

• Watts, Kaitlyn

Advisors dc:contributor.advisor

• Cobo, Eduardo R.
• Barkema, Herman W.

Committee members dc:contributor.committeemember

• De Buck, Jeroen M.
• Jenne, Craig N.

• Bovine digital dermatitis
• Treponema spp
• Cathelicidins
• Host defense peptides
• keratinocytes

Statement dc:rights

• University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.

Language dc:language.iso

eng

DOI

http://dx.doi.org/10.11575/PRISM/33084

OAI identifier oai:identifier

oai:ucalgary.scholaris.ca:1880/108731