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M Jeffrey,
L González,
A Espenes,
C McL Press,
S Martin,
M Chaplin,
L Davis,
T Landsverk, C MacAldowie,
S Eaton,
G McGovern
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ABSTRACT: To determine the mechanisms of intestinal transport of infection, and early pathogenesis, of sheep scrapie, isolated gut-loops were inoculated to ensure that significant concentrations of scrapie agent would come into direct contact with the relevant ileal structures (epithelial, lymphoreticular, and nervous). Gut loops were inoculated with a scrapie brain pool homogenate or normal brain or sucrose solution. After surgery, animals were necropsied at time points ranging from 15 min to 1 month and at clinical end point. Inoculum-associated prion protein (PrP) was detected by immunohistochemistry in villous lacteals and in sub-mucosal lymphatics from 15 min to 3.5 h post-challenge. It was also detected in association with dendritic-like cells in the draining lymph nodes at up to 24 h post-challenge. Replication of infection, as demonstrated by the accumulation of disease-associated forms of PrP in Peyer's patches, was detected at 30 days and sheep developed clinical signs of scrapie at 18-22 months post-challenge. These results indicate discrepancies between the routes of transportation of PrP from the inoculum and sites of de novo-generated disease-associated PrP subsequent to scrapie agent replication. When samples of homogenized inoculum were incubated with alimentary tract fluids in vitro, only trace amounts of protease-resistant PrP could be detected by western blotting, suggesting that the majority of both normal and abnormal PrP within the inoculum is readily digested by alimentary fluids.
The Journal of Pathology 06/2006; 209(1):4-14. · 6.32 Impact Factor
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The Veterinary record 04/2005; 156(13):420-1. · 1.25 Impact Factor
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ABSTRACT: A technique to take sequential tissue biopsy samples in multiparous, periparturient ewes from the abomasal mucosa is described, developed in parallel in Scotland and New Zealand. Samples were extracted via abomasal cannulae inserted into the wall of the abomasum and exteriorised through dorso-ventral laparotomy. Animals recovered quickly post-surgery, and tolerated the cannula and sampling without any adverse signs of pain or discomfort. The technique was deployed in two pilot studies to investigate the sequential mucosal inflammatory cell responses in well-defined parasitological models, during the periparturient relaxation of immunity in ewes infected with gastrointestinal nematodes and subjected to different feeding treatments. One experiment (Moredun Research Institute, Scotland) involved the infection of twin-bearing ewes with Teladorsagia circumcincta L3 either before, or after lambing. By feeding ewes with different levels of protein supplementation, preliminary data on the impact of nutrition on the eosinophil, mucosal mast cell and globule leucocyte responses during this period were investigated. A similar study was also performed at Lincoln University, New Zealand, to investigate these cell responses in sheep fed relatively high or low protein diets during pregnancy, and infected with a combined immunisation regime of T. circumcincta and Trichostrongylus colubriformis L3. These studies confirmed the phenomenon termed the periparturient relaxation in immunity (PPRI) where a transitory increase in faecal egg counts is observed during late pregnancy and lactation, and this effect was exacerbated during protein undernutrition. Although the number of animals was low in each experiment and the cell responses variable, the results together suggest a reduction in the number of mucosal mast cells and globule leucocyte during the PPRI when protein supply was restricted. The present paper thus describes a successful technique to monitor ovine mucosal cell populations during local immune responses in normal and pregnant sheep. It is envisaged that this technique will be a powerful adjunct to investigations into mucosal immune mechanisms and disease pathogenesis, and will be employed to confirm the influence of dietary protein on the local inflammatory cell responses during the PPRI.
Veterinary Immunology and Immunopathology 03/2004; 97(3-4):163-76. · 2.08 Impact Factor
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ABSTRACT: Larval development, mucosal mast cell (MMC) and eosinophil responses in worm-nai;ve lambs, yearling goats and goat kids were compared using two different experimental challenge regimes involving oral administration of infective Teladorsagia circumcincta L(3). Experimental challenge regimes enabled primary and secondary immune responses in the two species to be compared. Goats carried higher worm burdens than lambs and there were significant differences in the stages of development attained by the larval challenge that established in the two species. Possible physiological reasons for these differences are discussed. There were also differences in the establishment and development of larvae in individual yearlings which may indicate the development of a weak age-related immune response. Quantitative analysis of MMC and globule leukocyte (GL) recruitment and functional activity in the form of mast cell-specific proteinase (MCP) production demonstrated differences between the species with goat tissues containing significantly higher numbers of GL and lower concentrations of MCP than the lambs. Quantitative analysis of blood and tissue eosinophil responses failed to demonstrate any significant differences in either species under the two challenge regimes.
Veterinary Parasitology 06/2003; 114(1):1-13. · 2.58 Impact Factor
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ABSTRACT: Pregnant cattle were inoculated with N. caninum strain NC-1 tachyzoites intravenously (iv) (group 1, n = 8) or subcutaneously (sc) (group 2, n = 8) at 70 days' gestation. Control animals (group 3; n = 8) received uninfected Vero cells iv. Two animals from each group were killed at 14, 28, 42 and 56 days post-inoculation (dpi). Fetal mortality was 100% and 50%, respectively, in groups 1 and 2 from 28 dpi. In group 1 foci of degenerative fetal placental villi were observed at 14 dpi, with clusters of N. caninum tachyzoites in the affected mesenchyme. There was also inflammation of maternal septal tissues, with necrotic cell debris and serum exudate at the interstitium. At 28 dpi pregnancy had ended and the fetal cotyledons had become detached from the maternal caruncles. Immunohistochemically, particulate N. caninum antigen was detected in the cotyledons. At 42 and 56 dpi, fetal tissues had disappeared, the caruncles were greatly reduced in size, and the uterine epithelium had been largely restored. In group 2, lesions were either severe or absent ("all or nothing" response). In one animal carrying a dead fetus at 28 dpi, placentitis was much more severe than that seen in group 1 at 14 dpi. Lesions contained neutrophils, eosinophils and N. caninum antigen. In animals carrying dead fetuses at 42 and 56 dpi, fetal remains were found and the cotyledons contained N. caninum antigen. Antigen was also detected in fetal tissues. No significant pathological changes were detected in group 2 animals carrying live fetuses or any animal in group 3. Thus, N. caninum administered iv or sc in early pregnancy resulted in rapid fetal death, with parasite-associated lesions in the placenta and fetus. Of the two inoculation routes, the intravenous induced the more acute placental lesions and greater mortality.
Journal of Comparative Pathology 131(2-3):142-56. · 1.65 Impact Factor
