Abstract
In Lyme borreliosis, the skin is the key site of bacterial inoculation by the infected tick, and of cutaneous manifestations, erythema migrans and acrodermatitis chronica atrophicans. We explored the role of fibroblasts, the resident cells of the dermis, in the development of the disease. Using microarray experiments, we compared the inflammation of fibroblasts induced by three strains of Borrelia burgdorferi sensu stricto isolated from different environments and stages of Lyme disease: N40 (tick), Pbre (erythema migrans) and 1408 (acrodermatitis chronica atrophicans). The three strains exhibited a similar profile of inflammation with strong induction of chemokines (CXCL1 and IL-8) and IL-6 cytokine mainly involved in the chemoattraction of immune cells. Molecules such as TNF-alpha and NF-κB factors, metalloproteinases (MMP-1, -3 and -12) and superoxide dismutase (SOD2), also described in inflammatory and cellular events, were up-regulated. In addition, we showed that tick salivary gland extracts induce a cytotoxic effect on fibroblasts and that OspC, essential in the transmission of Borrelia to the vertebrate host, was not responsible for the secretion of inflammatory molecules by fibroblasts. Tick saliva components could facilitate the early transmission of the disease to the site of injury creating a feeding pit. Later in the development of the disease, Borrelia would intensively multiply in the skin and further disseminate to distant organs.
Highlights
Lyme borreliosis (LB) caused by spirochetes of the B. burgdorferi sl group is the most common vector-borne disease in the Northern Hemisphere
Fibroblasts Stimulated by B. burgdorferi ss N40, Pbre and 1408 Strains Secrete Inflammatory Genes
The skin is a major organ in the development of LB since it constitutes the inoculation site for Borrelia and tick saliva, and for the early and late manifestations, erythema migrans (EM) and ACA respectively [4,5]
Summary
Lyme borreliosis (LB) caused by spirochetes of the B. burgdorferi sl group is the most common vector-borne disease in the Northern Hemisphere. These bacteria are transmitted by the tick Ixodes spp. They participate in tissue homeostasis, leukocyte recruitment and inflammation regulation [8] Due to their broad and highly specialized roles in conditioning the cellular and cytokine/chemokine environment, resident sentinel fibroblasts function as part of the immune system [9]
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