Prion uptake in the gut: identification of the first uptake and replication sites.

After oral exposure, prions are thought to enter Peyer's patches via M cells and accumulate first upon follicular dendritic cells (FDCs) before spreading to the nervous system. How prions are actually initially acquired from the gut lumen is not known. Using high-resolution immunofluorescence and cryo-immunogold electron microscopy, we report the trafficking of the prion protein (PrP) toward Peyer's patches of wild-type and PrP-deficient mice.

Differential susceptibility of Sprague-Dawley and Fischer 344 rats to infection by Francisella tularensis.

The type A and B subspecies of Francisella tularensis cause severe disease, tularemia, in humans. However, only the former can be lethal especially if inhaled. It is likely that non-lethal infection is due at least in part to the ability of innate host defenses to control pathogen growth whilst acquired immunity develops.

In vivo depletion of CD11c+ cells impairs scrapie agent neuroinvasion from the intestine.

Following oral exposure, some transmissible spongiform encephalopathy (TSE) agents accumulate first upon follicular dendritic cells (DCs) in the GALT. Studies in mice have shown that TSE agent accumulation in the GALT, in particular the Peyer's patches, is obligatory for the efficient transmission of disease to the brain. However, the mechanism through which TSE agents are initially conveyed from the gut lumen to the GALT is not known.

Assessing the involvement of migratory dendritic cells in the transfer of the scrapie agent from the immune to peripheral nervous systems.

Many transmissible spongiform encephalopathy (TSE) agents accumulate upon follicular dendritic cells (FDCs) in lymphoid tissues before spreading to the brain. How TSE agents spread from FDCs to the nervous system is not known as there is no physical FDC-nerve synapse. As FDCs form immobile networks we investigated whether other mobile cells might transfer TSE agents between FDCs and peripheral nerves.

Effects of antigen and recombinant porcine cytokines on pig dendritic cell cytokine expression in vitro.

To evaluate variables influencing in vitro immune response induction, pig monocyte-derived DCs (moDCs) were treated with putative type-1 and type-2 antigens (Ags, killed Mycobacterium tuberculosis (Mtb) and hen egg white lysozyme (HEWL)) and recombinant porcine cytokines (IL-6, IL-10, IL-12, IFN-gamma and TNF-alpha). Responses were measured as moDC cytokine mRNA expression. Treatment of moDCs with HEWL increased IL-13 but not IL-12, IFN-gamma or IL-10 mRNA, suggesting a DC2 phenotype.

Toll-like receptor, MHC II, B7 and cytokine expression by porcine monocytes and monocyte-derived dendritic cells in response to microbial pathogen-associated molecular patterns.

To evaluate effects of treatment with pathogen-associated molecular patterns (PAMPs) on toll-like receptor (TLR), MHC II, B7 and cytokine expression, pig monocytes and monocyte-derived DCs (moDCs) were treated with LPS, CpG, lipoteichoic acid (LTA), poly IC or peptidoglycan (Pep). Monocytes and moDCs treated with LPS, CpG, LTA, poly IC or Pep altered expression of at least one TLR (4, 5 and 9) and up-regulated MHC II and/or B7. The mRNA for IL-4 was not detected after any treatment.

Th-1/Th-2 type cytokine profiles of pig T-cells cultured with antigen-treated monocyte-derived dendritic cells.

To examine the effects of cytokine environment at the time of antigenic exposure on T-cell cytokine profiles following T-cell-antigen presenting cell (APC) interaction, pig monocyte-derived dendritic cells (mDCs) were treated with hen egg white lysozyme (HEWL) or killed Mycobacterium tuberculosis (Mtb) alone or with a recombinant pig cytokine (TNF-alpha, interleukin (IL)-12, IL-10, interferon (IFN)-gamma or IL-6) and then incubated with autologous T-cell-enriched lymphocytes. Messenger RNA was isolated from the T-cells and used to evaluate the effects of treatment on IL-12p35, IFN-gamma, IL-4, IL-10 and IL-13 expression using RT-PCR. T-cells exposed to HEWL-treated mDCs expressed high IL-13 and moderate IL-10 and IFN-gamma, suggesting T-helper 2 (Th-2) bias.