A Differential Innate Immune Response in Active and Chronic Stages of Bovine Infectious Digital Dermatitis

Abstract

Digital dermatitis (DD) commonly associated with Treponema spp. infection is a prevalent infectious bovine foot disease characterized by ulcerative and necrotic lesions. Lesions associated with DD are often classified using the M-stage scoring system, with M0 indicating healthy heel skin and M4 indicating chronic lesions. Current treatments utilizing antimicrobials or chemical footbaths are often ineffective and rarely cure DD lesions. Understanding the function of the innate immune response in the pathogenesis of DD will help to identify novel therapeutic approaches. In this study, the expression of the local innate host defense peptides cathelicidins and β-defensins was investigated in cows with DD and associated with the presence of treponemes and inflammatory reactions. Samples from active ulcerative DD lesions (M2) had considerable epidermal neutrophilic infiltration and increased gene expression of β-defensin tracheal antimicrobial peptides compared to control skin. Samples from acute lesions also had elevated local Cxcl-8 and TLR4 gene expression and abundant treponemes as identified by direct visualization, immunohistochemistry, and culture. Conversely, the anti-inflammatory peptide IL-10 was elevated in skin from chronic (M4) lesions, whereas bovine cathelicidin myeloid antimicrobial peptide 28 (Bmap-28) was increased in skin from oxytetracycline-treated M2 lesions. Experiments using cultured human keratinocytes challenged with Treponema spp. isolated from clinical cases of bovine DD showed that structural products from treponemes are able to initiate the innate immune response, in part through TLR2 signaling. These findings indicate that neutrophil influx, Cxcl-8, and β-defensin are key markers of active DD. Cathelicidins and IL-10 seem important in response to treatment or during the chronic proliferative stages of the disease.

Proof of an optimized salicylic acid paste-based treatment concept of ulcerative M2-stage digital dermatitis lesions in 21 dairy cows

“…In recent years, BDD showed an increasing tendency to become a chronic disease [ 12 , 13 ]. Recurrence is frequently seen, indicating that natural immunity against spirochetes is not achieved, and that state-of-the-art prevention and control measures are not sufficiently effective [ 14 ].…”

Evaluation of Reproductive Tract Cytokines in Post-partum Beef Cows Relating to Reproductive Microbiota and Fertility Outcomes

“…Additionally, Treponema spp. is prevalent in infectious bovine foot disease resulting in necrotic lesions and lameness (Bay et al, 2018;Watts et al, 2018;Kontturi et al, 2019). These results demonstrate some pathogenic bacteria have positive relationships with pro-inflammatory cytokines and negative relationships with anti-inflammatory cytokines, which potentially could be affecting fertility.…”

Treponema spp. Isolated from Bovine Digital Dermatitis Display Different Pathogenicity in a Murine Abscess Model

“…There was higher transcriptional expression of IL-10 for T. medium versus T. phagedenis . It is noteworthy that IL-10 plays a role in suppressing inflammatory reactions, including in skin disorders [ 54 ] and downregulation of IL-10 occurs in active DD [ 55 ]. Chemoattractant CXCL-1 and regulatory TGF-β were unaffected, indicating responses of those factors could occur at posttranscriptional level or at later points.…”