Cutaneous inflammation during Lyme disease transmission : study on a murine model
Cutaneous inflammation during Lyme disease transmission : study on a murine model.
Thèses de doctorat,
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Lyme disease, is an infectious disorder caused by a tick-transmitted bacteria : Borrelia burgdorferi. The skin constitutes an essential interface in this arthropod borne disease. Indeed, the primary manifestation is a cutaneous inflammation, the erythema migrans. Dissemination of spirochetes from the site of inoculation can lead to other manifestations typically involving the skin, heart, joints or central nervous system. Mechanisms responsible of this specific dissemination are not known. In this project we focused on the cutaneous innate immune response during Lyme disease transmission. Part of skin innate immunity is constituted by the secretion of antimicrobial peptides (AMPs), cytokines and chemokines. We developed two experimental strategies. In vitro to measure the specific response from skin resident cells: keratinocytes. In vivo we challenged C3H/HeN mice with spirochetes from B. burgdoferi sensu stricto strains initially isolated from human clinical manifestation. In conclusion, we propose that tick saliva has a property not previously described: an anti-alarmin effect. Tick saliva is an essential actor in the pathogenesis of skin inflammation. Furthermore, we showed a clear difference in the skin innate immunity according to the strain tested. The skin by its immunity and the specificity of its different resident cells likely plays a major role in the development of Borrelia infection in the vertebrate host. There, an intense bacterial multiplication occurs. Some specific factors of both, the bacteria (like OspC and BBK32) and the host (like AMPs and MCP-1), display a sophisticated interaction that likely further orientate the bacterium in the rest of the body.
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