Distribution of nerve fibres and prion protein expression in mice Peyer’s patches

Prion pathogenesis following oral exposure is thought to involve gut-associated lymphoid tissue, which includes Peyer’s patches (PP). The antigens enter into the underlying lymphoid tissue organized in PP through the medium of M cells. Infectious prion protein (PrPres) would probably take the same way of entry and like this initiate the first stage of lympho-invasion. Theoretically, intestinal lymphoid cells can come in contact with ingested PrPres and with nerve endings of the intramural system. The distribution pattern of the nerve fibres and lymphoid cells in PP and possible contact between these two elements implicated in neuroinvasion are not yet fully elucidated.

In our study, classical immunoperoxydase staining and double immunofluorescence staining analysed with a confocal microscope has been carried out on C56Bl/6 mice PP. Immunoperoxidase and immunofluorescent CD11c stainings show numerous dendritic cells (DC) in the suprafollicular dome, close to the epithelium made of enterocytes and M-cells. Confocal studies show the presence of DC in the T cell zones of Peyer's patches, and also close to B cells in the follicule and to follicular dendritic cells (FDC) in the germinal centres. The PrPc expression, fundamental in the pathogenesis of prion diseases, is notably localized in germinal centres, co-localized with the FDC network and on cellular structures close to the epithelium, co-localized with DC. Nerve fibres have been immunostained in fluorescence using antibodies raised against neurofilaments High, Medium and Low and against glial fibrillary acidic protein (GFAP). Only GFAP staining revealed the presence of some nerve fibres in the suprafollicular dome, coursing the mucosal epithelium and also at the periphery of germinal centres in close connection with numerous dendritic cells.

Such results permit us to postulate that these nerve fibres and PrPc positive dendritic cells, strategically positioned under the intestinal epithelium as well as in the germinal centres close to FDC network, highly expressing PrPc and thought to replicate PrPres, may be involved in the peripheral transport of the infectious prion protein.