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1.
The development of eosinophilia is a characteristic feature of helminth infection, although the exact nature of the interaction between eosinophils and parasites remains to be fully defined. Previously, it has been reported that Haemonchus contortus and other nematodes produce eosinophil-specific chemoattractants. This paper describes studies aimed at isolating and identifying the factor(s) responsible. Initial studies showed that soluble extracts of infective larvae (L3) of H. contortus provoked a chemokinetic, rather than chemotactic, response in ovine bone marrow eosinophils in vitro. This activity was inhibited by lactose to a markedly greater extent than sucrose suggesting a galectin-like identity. Lactose affinity chromatography of soluble H. contortus extracts resulted in the isolation a specific bound fraction which retained biological activity. SDS-PAGE gel electrophoresis indicated a single Coomassie-stained band at between 31 and 41kDa. Subsequent, mass spectrometric analysis confirmed that the bound fraction contained a mixture of nematode galectins. The results confirm that H. contortus larvae produce several galectin-like proteins, at least one of which demonstrates eosinophil chemokinetic activity in vitro. The possibility of the parasite-derived factor mimicking the mammalian galectin-9, a known eosinophil chemokine, is discussed.  相似文献   

2.
Infections of sheep with the gastrointestinal nematode Teladorsagia circumcincta are characterised by increased concentrations of IgA, eosinophilia and mastocytosis but the interactions between these immune responses are unclear. We investigated the kinetics of the parasite-specific IgA and eosinophil responses in controlled infections in lambs to determine if there were any associations with subsequent worm growth and survival. IgA and eosinophil responses had very similar kinetics and variation in both responses accounted for more of the variation in adult worm length than either trait alone suggesting that IgA and eosinophils interact in regulating the growth of T. circumcincta. Curiously, those animals with higher peak eosinophil responses had longer worms at slaughter emphasising the intriguing complexity of the immune responses to these parasitic infections.  相似文献   

3.
Small ruminants are affected by gastrointestinal nematode (GIN) infection. A promising alternative strategy for control of GIN infection is to increase the level of resistance in the population by taking advantage of the host's immune response. Immunoglobulin A (IgA) and E (IgE) are known to be involved in immune response to GIN. The aim of this study was thus to investigate genetic parameters of IgA and IgE responses against Haemonchus contortus in Creole kids naturally challenged at pasture and to determine the relationship with other resistance criteria such as faecal egg counts, packed-cell volume, eosinophil counts and bodyweight. Variance and covariance components for genetic and residuals effects for each trait were estimated on 3862 males at 11 months of age. Heritability estimates for IgA and IgE ranged between 0.15 and 0.57. Strong positive genetic correlations were observed between either IgE or IgA responses against L3 and adult excretory/secretory products (ESP) antigens of H. contortus, suggesting that the humoral immune response is not specific to the life cycle stage of the parasite suggesting that there is substantial cross recognition between the different parasite antigens. Heritability estimates for faecal egg count (FEC), packed-cell volume (PCV) and bodyweight (BW) were in accordance with previous results in Creole kids. Blood eosinophil counts were found moderately heritable and negatively correlated with FEC, suggesting that this cell population plays a role in resistance to nematode parasite infection in Creole goats. IgA response was positively correlated to FEC, in contrast with the negative correlation between IgE against L3 of H. contortus and FEC. In Creole goats, IgA response against L3 or ESP of H. contortus would rather be associated with the worm burden than an immune protective response. The immune response involving activity of IgE against L3 of H. contortus may be one important pathway for development of resistance to gastrointestinal nematode infections in Creole goats.  相似文献   

4.
In May 2002, studies on the seasonal patterns of nematode infection of sheep were undertaken on four commercial sheep farms in southern Sweden, which had previously reported problems with nematode parasitism, especially due to Haemonchus contortus. One farm was used for intensive investigation. This entailed the establishment of two replicate groups of sheep, each consisting of 20 ewes and their lambs, on adjacent pasture paddocks. The seasonal patterns of nematode infection were followed by regular (approximately monthly) sampling of both ewes and lambs for nematode faecal egg counts and larval differentiation, and the sequential use of replicate groups of tracer lambs. H. contortus and Teladorsagia circumcincta were the most abundant nematode species, with the former most prevalent in the post-parturient faecal egg counts of ewes. Tracer worm counts showed almost 100% arrested development in the early fourth larval stage for H. contortus as early as mid-summer and the numbers of parasites progressively increased during the season. T. circumcincta also showed high levels of arrested development, but not as early, or as absolute, as for H. contortus. Tracers allocated to the paddocks at the time of turn-out following winter in May 2003, showed virtually a total absence of H. contortus in contrast to exceedingly high infections with T. circumcincta. Results of the three additional monitoring flocks supported these findings. It can be concluded that under Swedish sheep farming conditions, H. contortus has evolved to survive the long, cold winters entirely within the host as the arrested larval stage, relying on the lambing ewe to complete its life cycle. The peri-parturient relaxation of resistance in the ewes triggers the resumption of development to the adult egg-laying parasites to result in pasture contamination and the completion of just one parasite generation/year. In contrast, T. circumcincta can survive well over-winter, both on pasture and within the host.  相似文献   

5.
The effects of tannins on adult populations of Haemonchus contortus, Trichostrongylus colubriformis and Teladorsagia circumcincta in goats are characterised mainly by a decrease in egg excretion without any significant changes in worm number. In contrast, the impact of tannins on T. colubriformis or T. circumcincta third-stage larvae (L3) is associated with a significant reduction in worm establishment. The objective of the present study was to examine the effects of quebracho extract tannins on H. contortus L3. The consequences of consumption of sainfoin hay were also examined. Twenty-one na?ve kids were divided into three experimental groups. Group Q received quebracho extract and group S received sainfoin hay from days D3 to D5. Group C remained as an infected control group. All kids received 1500 L3 H. contortus on D0, D1 and D2. On D18, post-infection, the kids were slaughtered and the worm populations compared in the different groups. Compared to the control values, the worm counts decreased, respectively, by 33% and 38% in groups Q and S but the differences were not significant. No differences were found in pathophysiological measurements between the three groups. The results confirm differences in tannin effect according to nematode species but not parasitic stage.  相似文献   

6.
One of three groups of sheep was challenged twice-weekly with infective-stage larvae (L3) of the sheep parasite O. circumcincta, another with the cattle parasite O. ostertagi while the third received no larval challenge. Positive faecal egg counts (FEC) and a rise in plasma pepsinogen levels were observed only in those animals given O. circumcincta. Anti-O. circumcincta L3 IgG titres were rapidly elevated during parasite challenge with either O. circumcincta or O. ostertagi. Throughout the experiment, no rise in anti-adult IgG titres or eosinophil numbers was observed in peripheral blood in any group. On evidence of self-cure of the trickle-infection, determined by a reduction in FEC, all groups were drenched and challenged with 15,000 O. circumcincta L3. No effect of previous challenge on parasite establishment or FEC was observed, although egg viability was significantly reduced in both groups given prior challenge. Significant differences in adult female worm length were observed between groups. Those recovered from animals previously challenged with O. circumcincta were shorter than from those given O. ostertagi which were in turn shorter than those from previously unchallenged animals. In utero egg counts were significantly lower in worms from animals previously challenged with O. circumcincta than in those from unchallenged control animals. The results indicate that a level of immunity to O. circumcincta can be conferred by exposure to O. ostertagi.  相似文献   

7.
Canaria Hair Breed (CHB) sheep are more resistant than Canaria sheep (CS) to experimental Haemonchus contortus infection. Protective responses appear effective against the adult stage of the parasite, not as commonly reported in other breeds against the larval stages. In this study we have quantified several abomasal immune cells and correlated these with parasitological variables for each breed. A significant negative correlation between CD4+ T cell numbers and worm burden or length at 28 dpi was seen only in CS sheep. Significant negative correlations for both abomasal eosinophils and γδ/WC1+ T cells, and fecundity of the adult worms were observed only in the resistant CHB sheep breed. Tissue eosinophils and γδ/WC1+ T cells were positively correlated in CHB sheep. We suggest that the two sheep breeds have disparate immune responses following infection with the parasite and that γδ+ T cells in association with eosinophils may play a hitherto unrecognised role in modulating fecundity in H. contortus adult female parasites.  相似文献   

8.
Sera from 53 sheep belonging to Castellano, Churro, Manchego, and Merino breeds were analyzed to test the diagnostic value of a 26-kD antigen from adult Haemonchus contortus at prepatency and early and late patency of experimental haemonchosis. Animals that received zero, 1, or 2 infections with the parasite were tested. In addition, sera from 20 experimentally infected and 10 noninfected Texel sheep were used to test the antigen. Sera from 37 infected animals at prepatency as well as at patency in primary and secondary infection were found positive with the 26-kD antigen. However, sera from 10 animals with the lowest worm burdens (second infection) did not recognize the antigen during early patency (day 28 postinfection). IgG1 was the only isotype implicated in antigen recognition because IgG2, IgA, and IgM, in the same sera, showed no reactivity with the peptide. Antigen specificity was confirmed because hyperimmune sera against infective larvae and adult stages of the most common gastrointestinal nematodes found in natural infections in sheep (Trichostrongylus colubriformis and Teladorsagia circumcincta) did not recognize this peptide. The antigen was recognized only by anti-adult H. contortus hyperimmune sera and appeared to be absent in the L3 parasite stage. In addition, the partial N-terminal amino acid sequence of the diagnostic peptide is reported.  相似文献   

9.
Lectins are plant secondary compounds that can have anthelmintic properties in vitro. In particular, the phytohaemagglutinin lectin extracted from Phaseolus vulgaris has been shown to inhibit the feeding of Trichostrongylus colubriformis and Teladorsagia circumcincta L1 larvae. However, little is known about the potential anthelmintic properties of this lectin in vivo and its suitability to control gastrointestinal parasite infections in lambs. In a 2 × 2 study, lambs were either orally dosed, or not, with 2.3mg semi-purified PHA lectin per kg live weight (LW) per day, whilst concurrently infected, or not, with 1000 T. circumcincta and 1000 T. colubriformis L3 infective larvae per day for 42 days. There were no adverse clinical effects observed with this dose of PHA lectin. Although worm burdens were similar, animals dosed with PHA lectin had reduced concentration of nematode eggs in the faeces compared with their non-lectin dosed counterparts (P=0.026), suggesting that there may be a direct effect of PHA lectin on parasite fecundity. Irrespective of infection, PHA lectin had immune-stimulatory properties with increased eosinophillia in both abomasal and small intestine tissue sections taken at slaughter on day 42 (P<0.02 for both) and a tendency for decreased ability of Teladorsagia larvae to penetrate abomasal tissue explants (P=0.06). Compared with infection alone, concurrent PHA lectin dosing and infection further increased the number of eosinophils (P<0.01), PAS-positive (mucin-producing cells) (P=0.03) and tended to increase the number of T helper cells (P=0.06). No interactions were observed for cell populations in small intestine tissue sections. These results suggest PHA lectin could have two possible modes of action against T. circumcincta and T. colubriformis, a direct anthelmintic effect on nematode fecundity and an indirect effect through enhancing local immune responses in the host.  相似文献   

10.
A pen study was conducted to assess the effect of providing daily copper mineral supplement, or copper wire particle (COWP) capsules, on established or incoming mixed nematode infections in young sheep. For lambs with established (6 week old) infections, COWP resulted in 97% and 56% reduction of the adult and early L4 stages of H. contortus, respectively, compared with controls (p<0.001). Additionally there was a 74% reduction in Teladorsagia circumcincta infections in the COWP lambs compared with controls (p<0.01). However, no effect was observed when COWP were given at the commencement of a larval dosing period of 6 weeks. There was no significant effect of copper mineral supplement (given at the recommended rate to prevent Cu deficiency) on either established, or developing parasite infections. In addition, a field trial was conducted on a commercial farm to assess the effects of COWP in the management of recurrent H. contortus infections, but lack of parasites during the grazing season prevented an adequate assessment from being made. These results indicate that there is little, if any, benefit from a parasite control standpoint in recommending copper therapy, specifically to control parasites in Swedish sheep flocks.  相似文献   

11.
36 intact male and 69 female lambs of two breeds (n = 63 Merinoland; n = 42 Rh?n) aged 12 weeks were orally infected with 5000 infective-stage larvae, L3, of the nematode Haemonchus contortus. After 4 and 8 weeks faecal egg counts (FEC), haematocrit values and plasma testosterone levels were determined. All lambs were slaughtered at 20 weeks of age. The gastrointestinal tracts were examined for the presence of adult stages of H. contortus. Male lambs showed significantly higher log FEC (p < 0.001), higher mean establishment rates (p < 0.05), higher worm burdens (p < 0.01) and lower haematocrit values (p < 0.001) when compared with female lambs. Correlations between economically important traits (body weight, daily weight gain) and parasitological parameters were significantly higher in male animals. Testosterone level was 4 weeks after infection significantly positive correlated with worm burden. The results suggest that female lambs are more resistant against an experimental H. contortus infection when compared with male lambs. Testosterone seems to play an important role in resistance. This approach can be of importance if parasite resistance is incorporated into breeding programs and the estimated breeding values for rams are only based on male offspring information. Therefore male breeding values are probably not representative for the whole population.  相似文献   

12.
Groups of four stag fawns, weighing 51 +/- 0.8 kg, were-infected with 30,000 larvae of one of three nematode parasites: O.circumcincta, O.ostertagia, or H.contortus. A further four remained as control. Individual feed intake, body-weight, faecal egg count and plasma pepsinogen concentration were measured during seven weeks after infection. Only infection with H.contortus caused significant elevation of pepsinogen concentration to 380ml/ L and consistent depression of feed intake (15%). Worm egg counts were below 300 e.p.g. in deer infected with all worm species. It is concluded that while resistance to development of parasites common to other species appears to be high further investigation of the susceptibility of deer to H. contortus infection would be justifiable.  相似文献   

13.
The neurotransmitter serotonin (5-hydroxy tryptamine or 5HT) regulates key physiological processes in nematodes such as locomotion and feeding. PAPP (p-amino-phenethyl-m-trifluoromethylphenyl piperazine) is a known agonist of the 5-HT(1Hc) receptor of the barber pole worm, Haemonchus contortus. In this study, PAPP was highly active against L3-stage larvae of H. contortus and Trichostrongylus colubriformis in an in vitro larval migration assay, with EC50 values of 9.36 and 11.8 microM, respectively, that were comparable to levamisole (10.2 microM) and superior to pyrantel (55.39 microM). When administered orally or subcutaneously to nematode infected gerbils, PAPP provided >99% efficacy against H. contortus and >98% efficacy against Teladorsagia circumcincta at 100 mg/kg, comparable to levamisole at 10 mg/kg. Drug titration revealed significant activity down to 50 mg/kg against these two species. Spectrum was limited, however, with somewhat lower efficacy (83%) in T. colubriformis infected gerbils at 100 mg/kg. Oral delivery of hydrochloride, acetate and phosphate salts of PAPP to nematode infected gerbils did not result in an increase in either potency or spectrum. The finding that PAPP exhibits significant anthelmintic activity suggests that the nematode-specific serotonergic system is a viable target for future anthelmintic discovery.  相似文献   

14.
Cellular changes in the abomasal tissue and draining abomasal lymph nodes were examined after primary infection of lambs with Haemonchus contortus for 3, 5 or 27-36 days.Infection with H. contortus larvae resulted in a rapid and selective increase in the percentage of CD4(+) T-cells in the abomasal lymph node at 3 days post-infection (PI). By 5 days PI, the lymph node weight had increased two-fold; however, the percentage of lymphocyte populations in the abomasal lymph node resembled that seen in uninfected sheep. Lymph node weights remained at increased levels in the adult nematode infected sheep and down-regulation of B-cell surface markers (sIg and MHC Class II) was apparent in this group. Significant increases in the percentage of CD4(+) T-cells co-expressing MHC Class II, but not CD25, were observed in the larval infected groups except in adult nematode infected sheep. Increased numbers of eosinophils, CD4(+), gamma delta(+) T-cells and B-cells were found in the abomasal tissue by 5 days PI, but no further increases in these cell populations were observed in the adult nematode infected group. In contrast, the level of both lamina propria and intraepithelial mast cells observed in the abomasal mucosa was highest in the sheep carrying an adult nematode burden. These findings indicate that sheep are able to generate an early immune response to infection with H. contortus larvae, characterised by the activation of CD4 T-cells and B-cells in the draining lymph nodes and recruitment of eosinophils, CD4(+) and gamma delta-TCR,WC1(+) T-cells and B-cells in larval infected tissues. However, these changes do not seem to be maintained during infection with the adult parasite where increases in mast cell numbers dominate the local response, indicating that different parasite stages may induce distinct and possibly counteractive immune responses.  相似文献   

15.
Results of real-time PCR analysis of coproculture third stage larvae (L3) using genus specific TaqMan minor groove binder probes were compared with the results of morphological differentiation of L3 after coprocultured and direct morphological worm differentiation from gastrointestinal samples of eight sheep with naturally acquired nematodes infections. Faecal egg counts prior to postmortem confirmed infections with trichostrongyles with a geometric mean count of 4828 eggs per gram for all sheep. Individual egg counts correlated positively with total worm counts (correlation coefficient 0.794). Five different nematode species and one genus were found in the abomasi and small intestines: Cooperia curticei, Haemonchus contortus, Nematodirus spp., Teladorsagia (Ostertagia) circumcincta, Trichostrongylus axei and Trichostrongylus colubriformis. Coproculture of faecal eggs yielded five of these, Cooperia spp., Haemonchus spp., Ostertagia/Teladorsagia spp. and Trichostrongylus spp. Comparison between morphological L3 and worm differentiation data showed high congruence (94%). The agreement between PCR analysis of L3 after coproculture and direct morphological worm differentiation was 84%. Thus, real-time PCR was found to be suitable as a speedy and reliable diagnostic tool for the assessment of gastrointestinal nematode infections of ruminants in the field.  相似文献   

16.
Monepantel is the first compound from the recently discovered amino-acetonitrile derivative (AAD) class of anthelmintics to be developed for use in sheep. Three dose determination studies were conducted in Australia and Switzerland to identify the minimum therapeutic dose of monepantel when formulated for the oral treatment of sheep to control fourth stage (L4) gastro-intestinal nematode larvae. In each study, sheep infected with the target nematodes (selected from Haemonchus contortus, Teladorsagia (Ostertagia) circumcincta, Teladorsagia trifurcata, Trichostrongylus axei, Trichostrongylus colubriformis, Trichostrongylus vitrinus, Cooperia curticei, Cooperia oncophora, Nematodirus battus, Nematodirus filicollis, Nematodirus spathiger, Chabertia ovina and Oesophagostomum venulosum) were treated with either 1.25, 2.5 or 5.0mg monepantel/kg liveweight. Following euthanasia and worm counting, efficacy was calculated against worm counts from untreated control groups. Monepantel proved highly effective at 2.5 and 5.0mg/kg, but was only moderately effective against some nematode species (L4 stage) at 1.25mg/kg. The results also confirmed that monepantel will effectively control L4 stages of nematodes resistant to at least some of the currently available broad-spectrum anthelmintic classes (macrocyclic lactone resistant strains were not included in the studies). It was concluded that 2.5mg/kg would be a suitable minimum dose rate for a commercial product. No adverse events related to treatment with monepantel were detected.  相似文献   

17.
The histological changes in the abomasal mucosa of pairs of worm-free ewes and lambs were compared at various stages after infection and reinfection with 350 Haemonchus contortus L3 per kg bodyweight. In terms of worm burdens the ewes were relatively resistant to reinfection compared with the lambs and the histological changes in the abomasum at most stages after infection were more marked in the adult animals. These included increases in the numbers of mast cells, globule leucocytes, eosinophils and IgA plasma cells in the mucosa.  相似文献   

18.
Primary and secondary serum antibody responses to Haemonchus contortus were studied in Castellana sheep. Ten-month-old sheep were infected (200 L3/kg live weight (lw)) and challenged (400 L3/kg lw) or uninfected and equally challenged with H. contortus. Primary infections induced a partially protective response upon challenge, characterized by higher serum protein levels, longer prepatent periods, lower fecal egg counts, and significant reduction in the establishment rate of the parasite and abomasal adult and L4 worm burdens. The resistant status of the infected and challenged sheep was not clearly related either to the serum specific antibody levels (IgG: IgG1, IgG2; IgM; IgA) estimated by ELISA or to immunodetection patterns in the Western blots.  相似文献   

19.
A 66 kDa adult Haemonchus contortus excretory/secretory (E/S) antigen was identified in Western blot by reaction with sera from the infected goats. The protein was purified from the adult worm extract and E/S products by anion exchange and ConA-Sepharose chromatography. The purified protein inhibited monocyte function in vitro as judged by decreased production of hydrogen peroxide and nitric oxide in the culture medium. The protein also caused proliferation of peripheral blood mononuclear cells. The absence of protein in the free living L3 larvae suggests that the expression of this protein coincides with the adaptation to the parasitic life. A correlation of antibody titre and worm burden was observed in the infected goats with higher antibody levels in high worm burdened animals. Anti-protein antibody caused loss of adult worm motility in vitro resulting in the death of the parasite. The fact that the protein is recognized by the host together with in vitro killing of adult parasites by antibodies makes this protein a promising candidate for vaccination trial.  相似文献   

20.
Two of the most important questions for immunologists studying nematode infections are what effect does the host response have on the parasite and which components of the host response are responsible for these effects. The number of nematodes and the mean length of adult female Ostertagia circumcincta was measured in over 500 6-7 month old lambs of the Scottish Blackface breed. Quantitative genetic analyses indicated that there was substantial genetic variation among lambs in faecal egg counts and in worm length but the analyses provided no evidence for genetic variation in worm numbers. Separate analyses have shown a strong relationship between decreased worm length and decreased worm fecundity. Therefore, genetic resistance in lambs appears to be due to control of worm growth and not to control of worm numbers. The only immune response that is consistently associated with reduced worm length is the IgA response to fourth-stage larvae. The association is remarkably strong. After allowing for the influence of worm number on worm length (density-dependence) essentially all of the variation among deliberately infected lambs in worm length can be accounted for, in a statistical sense, by variation in the strength and specificity of the local IgA response. Therefore, the IgA mediated suppression of worm growth and fecundity appears to be the major mechanism of resistance to O. circumcincta in lambs.  相似文献   

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