Affiliation:
1. Faculty of Veterinary Medicine, University of Calgary, Calgary, Canada
2. Department of Physiology & Pharmacology, Cumming School of Medicine, University of Calgary, Calgary, Canada
Abstract
ABSTRACT
Digital dermatitis (DD) is a skin disease in cattle characterized by painful inflammatory ulcerative lesions in the feet, mostly associated with local colonization by
Treponema
spp., including
Treponema phagedenis
. The reason why most DD lesions remain actively inflamed and progress to chronic conditions despite antibiotic treatment remains unknown. Herein, we show an abundant infiltration of proinflammatory (CD14
high
CD16
low
) monocytes/macrophages in active DD lesions, a skin response that was not mitigated by topical treatment with oxytetracycline. The associated bacterium,
T. phagedenis
, isolated from DD lesions in cattle, when injected subcutaneously into mice, induced abscesses with a local recruitment of Ly6G
+
neutrophils and proinflammatory (Ly6C
high
CCR2
+
) monocytes/macrophages, which appeared at infection onset (4 days post challenge) and persisted for at least 7 days post challenge. When exploring the ability of macrophages to regulate inflammation, we showed that bovine blood-derived macrophages challenged with live
T. phagedenis
or its structural components secreted IL-1β via a mechanism dependent on the NLRP3 inflammasome. This study shows that proinflammatory characteristics of monocytes/macrophages and neutrophils dominate active non-healing ulcerative lesions in active DD, thus likely impeding wound healing after antibiotic treatment.
Funder
Gouvernement du Canada | Natural Sciences and Engineering Research Council of Canada
Ministry of Advanced Education, Government of Alberta
Alberta Agriculture and Forestry
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology