Submitted to: Veterinary Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/5/2007
Publication Date: 6/13/2007
Citation: Zuerner, R.L., Heidari, M., Elliott, M.K., Alt, D.P., Neill, J.D. 2007. Papillomatous Digital Dermatitis Spirochetes Suppress the Bovine Macrophage Innate Immune Response. Veterinary Microbiology. 125(2007):256-264.
Interpretive Summary: Papillomatous digital dermatitis (PDD) is the primary cause of lameness in dairy cattle. PDD is an infection of soft tissue adjacent to the hoof and can cause considerable pain to the animal. This leads to a loss in milk production and may lead to premature culling of afflicted animals. PDD lesions contain a variety of different bacteria, but spirochetes are common to all lesions and are thought to be important in the progression of disease. This study focused on the response of bovine macrophages, a cell important in protecting animals during the early stages of infection, to bacterial material. Changes in gene expression were noted, and a trend was established that showed the treated macrophages failed to mount a strong inflammation response to the bacterial components. These findings suggest that the bacteria suppress the host response to infection, and enable the bacteria to establish lesions and evade the immune system.
Technical Abstract: Papillomatous digital dermatitis (PDD) is a polymicrobial infection in soft tissue adjacent to the hoof and is the leading cause of lameness in dairy cattle. Treponema phagedenis-like (TPL) spirochetes are a constant feature of PDD lesions and are localized deep in infected tissue. Host-cell response mechanisms to TPL bacteria are poorly understood. To assess how bovine macrophages respond to cellular constituents of TPL spirochetes, changes in transcription were analyzed using serial analysis of gene expression (SAGE) and real time RT-PCR. This analysis revealed that bovine macrophages responded to stimulation with TPL-lysates by induction of several pro-apoptotic genes. Although several proinflammatory cytokines (eg. IL-6 and IL-8) are induced in treated macrophages, receptors and their accessory proteins for IL-1, IL-6, and IL-11 are either down regulated or unchanged. Surprisingly, IL-1beta is not induced and IL-18 is suppressed in treated macrophages. Two genes encoding proteins having negative effects on NFkB, IkB and Siva-1, are significantly induced in stimulated cells. Combined, these data suggest that the innate immune response of bovine macrophages exposed to TPL cellular constituents are impaired thereby enabling bacteria to resist clearance and induce lesion formation.