Natural Mycoplasma Infection Reduces Expression of Pro-Inflammatory Cytokines in Response to Ovine Footrot Pathogens.

Ovine footrot is a complex multifactorial infectious disease, causing lameness in sheep with major welfare and economic consequences. is the main causative bacterium; however, footrot is a polymicrobial disease with , and also associated. There is limited understanding of the host response involved. The proinflammatory mediators, interleukin (IL)-1β and C-X-C Motif Chemokine Ligand 8 (CXCL8), have been shown to play a role in the early response to in dermal fibroblasts and interdigital skin explant models. To further understand the response of ovine skin to bacterial stimulation, and to build an understanding of the role of the cytokines and chemokines identified, primary ovine interdigital fibroblasts and keratinocytes were isolated, cultured and stimulated. The expression of mRNA and protein release of CXCL8 and IL-1β were measured after stimulation with LPS, or , which resulted in increased transcript levels of IL-1β and CXCL8 in the -free cells. However, only an increase in the CXCL8 protein release was observed. No IL-1β protein release was detected, despite increases in IL-1β mRNA, suggesting the signal for intracellular pre-IL-1β processing may be lacking when culturing primary cells in isolation. The keratinocytes and fibroblasts naturally infected with showed little response to the LPS, a range of preparations or heat-inactivated . Primary single cell culture models complement ex vivo organ culture models to study different aspects of the host response to . The ovine keratinocytes and fibroblasts infected with had a reduced response to the experimental bacterial stimulation. However, in the case of footrot where spp. are associated with diseased feet, this natural infection gives important insights into the impact of multiple pathogens on the host response.