Acquisition of antigens by airway dendritic cells. Do we know enough?

The respiratory system is endowed with a number of structural and functional barriers that protect it against harmful and innocuous material from taking advantage of its vast surface area to gain access into the organism. These barriers include; 1) the surfactant system 2) a highly efficient mucociliary escalator system 3) a population of highly phagocytic macrophages and 4) an epithelium endowed with tight junctions. However, despite these barriers, pulmonary immune responses are easily generated by introduction of antigens into the airways. These responses are thought to be mediated via dendritic cells, which are located in the basal aspect of the epithelium,and the most potent antigen presenting cells in the lung. Although there is substantial information on the nature of interaction between dendritic cell and particles from in vitro experiments, there is little information on how the particles breach the barrier to reach the immunocompetent cells. An understanding of how these particles pass the epithelial barrier to reach the immunocompetent cells is important in the development of mucosal vaccines. Insights into how this may happen are discussed.Keywords: Immune Cells, Respiratory Trac

Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection

In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system (LRS) long before they are detectable in the central nervous system. While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of lymphoid organs, the contribution of various other cell types, including antigen-presenting cells, to the accumulation and the spread of prions in the LRS are not well understood. A comprehensive study to compare prion titers of candidate cell types has not been performed to date, mainly due to limitations in the scope of animal bioassays where prohibitively large numbers of mice would be required to obtain sufficiently accurate data. By taking advantage of quantitative in vitro prion determination and magnetic-activated cell sorting, we studied the kinetics of prion accumulation in various splenic cell types at early stages of prion infection. Robust estimates for infectious titers were obtained by statistical modelling using a generalized linear model. Whilst prions were detectable in B and T lymphocytes and in antigen-presenting cells like dendritic cells and macrophages, highest infectious titers were determined in two cell types that have previously not been associated with prion pathogenesis, plasmacytoid dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK cells were more than twice, and pDCs about seven-fold, as infectious as lymphocytes respectively. This result was unexpected since, in accordance to previous reports prion protein, an obligate requirement for prion replication, was undetectable in pDCs. This underscores the importance of prion sequestration and dissemination by antigen-presenting cells which are among the first cells of the immune system to encounter pathogens. We furthermore report the first evidence for a release of prions from lymphocytes and DCs of scrapie-infected mice ex vivo, a process that is associated with a release of exosome-like membrane vesicles

Ethnoveterinary Medicine: The prospects of integrating medicinal plant products in Veterinary Medicine in Kenya

Animal diseases are a major constraint to livestock production, drought animal power and the acceptability of companion animals. These diseases also impact negatively to the food security in our country. The use of synthetic drugs for disease management is always a challenge because of the unavailability of these drugs especially in rural areas, shortage of foreign exchange to import them, lack of finance to purchase them, drug resistance, misuse due to paucity of knowledge and environmental pollution. Medicinal plants products are part of the natural products that have been in use in traditional medicine and also a source of novel drugs. Therefore, the use of medicinal plant products would be a rational alternative to synthetic drugs. Ethnobotanical surveys carried out in many parts of Kenya have revealed a lot of plants being used in animal disease management. Specific plant extracts have been identified and screened by many researchers for their antimicrobial, anthelmintic, acaricidal, antiprotozoal activity and also their toxicity. There is therefore the need to look for ways on how these plants products will be available in the market and be integrated in the overall veterinary medicine practice in Kenya

Host cell responses of Salmonella typhimurium

Live attenuated Salmonella are attractive vaccine candidates for mucosal application because they induce both mucosal immune responses and systematic immune responses. After breaking the epithelium barrier, Salmonella typhimurium is found within dendritic cells (DC) in the Peyer's patches. Although there are abundant data on the interaction of S. typhimurium with murine epithelial cells, macrophages and DC, little is known about its interaction with human DC. Live attenuated S. typhimurium have recently been shown to efficiently infect human DC in vitro and induce production of cytokines. In this study, we have analysed the morphological consequences of infection of human DC by the attenuated S. typhimurium mutant strains designated PhoPc, AroA and SipB and the wild-type strains of the American Type Culture Collection (Manassas, VA, USA), ATCC 14028 and ATCC C53, by electron microscopy at 30 min, 3 h and 24 h after exposure. Our results show that genetic background of the strains profoundly influence DC morphology following infection. The changes included (i) membrane ruffling; (ii) formation of tight or spacious phagosomes; (iii) apoptosis; and (iv) spherical, pedunculated membrane-bound microvesicles that project from the plasma membrane. Despite the fact that membrane ruffling was much more pronounced with the two virulent strains, all mutants were taken up by the DC. The microvesicles were induced by all the attenuated strains, including SipB, which did not induce apoptosis in the host cell. These results suggest that Salmonella is internalized by human DC, inducing morphological changes in the DC that could explain immunogenicity of the attenuated strains