Determining the role of mononuclear phagocytes in prion neuroinvasion from the skin

Journal of Leukocyte Biology

Gwennaelle J. Wathne¹  Adrien Kissenpfennig²  Bernard Malissen⁴  Chiara Zurzolo and³  Neil A. Mabbott¹ 

[1] The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, United Kingdom; Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University of Belfast, Northern Ireland, United Kingdom;Institut Pasteur, Unité Trafic membranaire et Pathogenèse, Paris Cedex, France The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, United Kingdom;Centre d'Immunologie de Marseille-Luminy, Université de la Méditerranée, INSERM, U63, CNRS, UMR60 Case 906, Cedex, France;

关键词: transmissible spongiform encephalopathy;    Langerhans cells;    dendritic cells;    neutrophils;    follicular dendritic cell;    PrP;   

DOI  :  10.1189/jlb.1211633

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Many prion diseases are acquired by peripheral exposure, and skin lesions are an effective route of transmission. Following exposure, early prion replication, upon FDCs in the draining LN is obligatory for the spread of disease to the brain. However, the mechanism by which prions are conveyed to the draining LN is uncertain. Here, transgenic mice were used, in which langerin+ cells, including epidermal LCs and langerin+ classical DCs, were specifically depleted. These were used in parallel with transgenic mice, in which nonepidermal CD11c+ cells were specifically depleted. Our data show that prion pathogenesis, following exposure via skin scarification, occurred independently of LC and other langerin+ cells. However, the depletion of nonepidermal CD11c+ cells impaired the early accumulation of prions in the draining LN, implying a role for these cells in the propagation of prions from the skin. Therefore, together, these data suggest that the propagation of prions from the skin to the draining LN occurs via dermal classical DCs, independently of langerin+ cells.

【 授权许可】

Unknown