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The role of JAM-C in innate leukocyte migration and the immune response to Leishmania major infection

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Defense Thèse de doctorat : Univ. Genève, 2015 - Sc. 4772 - 2015/03/11
Abstract Leishmaniasis is a parasitic disease transmitted to humans through sand fly bites. Clinical symptoms vary from self-healing cutaneous lesions to death. Cutaneous leishmaniasis is particularly studied in mice inoculated with Leishmania major. In this model, some strains (e.g. C57BL/6) are resistant due to a Th1 immune response promoting parasite killing. Conversely, other strains (e.g. BALB/c) are susceptible due to a nonprotective Th2 response. DCs are professional antigen-presenting cells that educate antigen-specific T cells. Improving the migration of DCs from the site of infection to the lymph nodes, where T cells reside, may improve the T cell response. JAM-C is a vascular adhesion molecule implicated in leukocyte migration in different inflammatory models. We found that JAM-C blockade with antibodies increases vascular permeability and consequently improves the migration of DCs to sites of infection and draining lymph nodes. This increased leukocyte migration boosted the induction of the Th1 response in resistant mice, while in susceptible mice the Th2 response was augmented. This led to disease improvement or exacerbation, respectively. Our results illustrate the key role of a vascular adhesion molecule in controlling leukocyte migration and the subsequent immune events in response to pathogen infections.
Keywords JAM-CDendritic cellsLeishmania major
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URN: urn:nbn:ch:unige-556506
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BALLET, Romain Roger. The role of JAM-C in innate leukocyte migration and the immune response to Leishmania major infection. Université de Genève. Thèse, 2015. https://archive-ouverte.unige.ch/unige:55650

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Deposited on : 2015-04-20

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