Core alpha1-->3-fucose is a common modification of N-glycans in parasitic helminths and constitutes an important epitope for IgE from Haemonchus contortus infected sheep.
(1/57)
Synthesis of parasite specific IgE plays a critical role in the defence against helminth infections. We report here that IgE from serum from Schistosoma mansoni infected mice and Haemonchus contortus infected sheep recognizes complex-type N-glycans from Arabidopsis thaliana, which contain R-GlcNAcbeta1-->4(Fucalpha1-->3)GlcNAcbeta1-Asn (core alpha1-->3-Fuc) and Xylbeta1-->2Manbeta1-->4GlcNAcbeta1-R (core beta1-->2-Xyl) modifications, and honeybee phospholipase A2, which carries N-glycans that contain the core alpha1-->3-Fuc epitope. Evidence is presented that core alpha1-->3-fucosylated N-glycans bind a substantial part of the parasite specific IgE in serum of H. contortus infected sheep. These results suggest that the core alpha1-->3-Fuc antigen may contribute to induction of a Th2 response leading to the production of IgE. In addition we show here that N-glycans carrying core alpha1-->3-Fuc and beta1-->2-Xyl antigens are synthesized by many parasitic helminths and also by the free living nematode Caenorhabditis elegans. Since N-glycans containing the core alpha1-->3-Fuc have also been implicated in honeybee and plant induced allergies, this conserved glycan might represent an important common IgE epitope. (+info)
Induction of T helper 1- and T helper 2-type immune responses during Haemonchus contortus infection in sheep.
(2/57)
The production of cytokines by lymphoid cells, isolated from non-infected and Haemonchus contortus-infected lambs, was investigated. Particular attention was paid to differences in T helper 1- (Th1) and Th2-type immune profiles between genetically resistant and random-bred animal groups. Non-infected resistant and random-bred lambs produced equivalent levels of interferon-gamma (IFN-gamma) and interleukin-5 (IL-5), from isolated abomasal lymph node cells (ALN), mesenteric lymph node cells (MLN) and spleen cells (SC), in response to in vitro stimulation with T-cell mitogen (concanavalin A) or larval parasite antigen. ALN and MLN cells derived from infected resistant and random-bred lambs produced relatively lower levels of IFN-gamma, following in vitro stimulation with parasite antigen, when compared with their uninfected counterparts. In contrast, infected lambs of both groups showed enhanced mitogen- and antigen-stimulated production of IL-5, in comparison with uninfected controls, at days 5 and 28 postinfection (p.i.). Mitogen- and antigen-stimulated IL-5 responses were higher among resistant lambs compared with random-bred lambs, with the highest overall production of IL-5 by parasite antigen-stimulated ALN and MLN cells. Among day 28 p.i. lambs, levels of cell culture-derived parasite-specific immunoglobulin G1 (IgG1) and IgE antibodies were higher in resistant lambs than in random-bred lambs, following in vitro stimulation of SC or ALN cells with parasite antigen. Finally, after 28 days p.i., histological examination of abomasal tissue revealed higher densities of mast cells and eosinophils in the mucosa of resistant lambs than in random-bred lambs. Taken together, these data support the notion of a strong Th2-type immune response to Haemonchus infection in genetically resistant sheep, and support the claim for a Th1/Th2 dichotomy in ruminants. (+info)
Isolation and characterization of a novel inducible mammalian galectin.
(3/57)
A novel mammalian galectin cDNA (ovgal11) was isolated by representational difference analysis from sheep stomach (abomasal) tissue infected with the nematode parasite, Haemonchus contortus. The mRNA is greatly up-regulated in helminth larval infected gastrointestinal tissue subject to inflammation and eosinophil infiltration. Immunohistological analysis indicates that the protein is localized in the cytoplasm and nucleus of upper epithelial cells of the gastrointestinal tract. The protein is also detected in mucus samples collected from infected abomasum but not from uninfected tissue. The restricted and inducible expression of ovgal11 mRNA and limited secretion of the protein support the hypothesis that OVGAL11 may be involved in gastrointestinal immune/inflammatory responses and possibly protection against infection. (+info)
Serodiagnosis of haemonchosis with a somatic antigen (Hc26) in several breeds of sheep.
(4/57)
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. (+info)
An anthelmintic compound, nafuredin, shows selective inhibition of complex I in helminth mitochondria.
(5/57)
Infections with parasitic helminths are important causes of morbidity and mortality worldwide. New drugs that are parasite specific and minimally toxic to the host are needed to counter these infections effectively. Here we report the finding of a previously unidentified compound, nafuredin, from Aspergillus niger. Nafuredin inhibits NADH-fumarate reductase (complexes I + II) activity, a unique anaerobic electron transport system in helminth mitochondria, at nM order. It competes for the quinone-binding site in complex I and shows high selective toxicity to the helminth enzyme. Moreover, nafuredin exerts anthelmintic activity against Haemonchus contortus in in vivo trials with sheep. Thus, our study indicates that mitochondrial complex I is a promising target for chemotherapy, and nafuredin is a potential lead compound as an anthelmintic isolated from microorganisms. (+info)
Pathological and immunohistochemical study of the abomasum and abomasal lymph nodes in goats experimentally infected with Haemonchus contortus.
(6/57)
Histopathological changes and the distributions of T and B lymphocytes and IgG producing plasma cells were recorded in the abomasum and abomasal lymph nodes of goats 3, 7 and 21 weeks post-infection (wpi) after an experimental infection with H. contortus. The low rate of worm recovery by 3 wpi (5.6%) might have been due to larvae death as suggested by the presence of granulomas in the abomasal mucosa at 3 and 7 wpi, or simply due to a poor larval establishment. Marked increase in the secretion of mucus by mucous cells together with an abundant infiltration of eosinophils, mast cells, CD3+ T lymphocytes, CD79a+ B cells, IgG+ plasma cells and globule leukocytes were recorded in the abomasal mucosa, especially at 7 wpi. Except for the globule leukocytes, this reaction decreased substantially by week 21, suggesting this cell type may have been involved in rejection of adult nematodes. The abomasal lymph nodes showed marked hyperplasia, particularly of CD79a+ B cells and IgG+ plasma cells in all infected goats. These reactions may have been responsible for the reduction in the number of worms found in the abomasum between 3 and 7 wpi. (+info)
The FAMACHA system for managing haemonchosis in sheep and goats by clinically identifying individual animals for treatment.
(7/57)
Escalating anthelmintic resistance has made it essential to develop alternative ways of worm management for reducing selection for worm resistance, and one of the most promising approaches is to treat only those animals unable to cope with worm challenge, thus favouring unselected worms originating from untreated animals. Only clinical evaluation of anaemia (FAMACHA system) and the body condition score are regarded as being of practical value or having potential, respectively, for repeatedly examining flocks or herds and identifying individuals for treatment. Only the FAMACHA system has been tested well enough for use under practical farming conditions. However, further investigation is needed on its effect on animal production, and methods to reduce labour. Trials over several seasons showed that most sheep under severe Haemonchus contortus challenge required no, or only one treatment over a full summer season. A small minority (usually < 5%) needed more than two treatments. Most sheep could cope without regular treatment. With sufficient training, clinical evaluation of anaemia was found reliable for practical use. The overwhelming majority of trainees (some poorly literate) were able to implement the FAMACHA system successfully. The dynamics of haemonchosis in a flock can easily be monitored. Farmers, farm workers and veterinarians all rated the system very highly (> 80%) and treatment costs dropped by approximately 58%. The heritability of FAMACHA values obtained by clinical evaluation was high at 0.55 +/- 0.17% in a Merino stud with +/- 550 young rams and ewes which were the progeny of 21 sires. The FAMACHA system may not be as applicable to goats as to sheep, but further work is necessary. The main benefits of the system are the reduction in treatments, its use for discriminating between animals of varying ability to cope with infection (thus allowing genetic selection), and its lowering of selection pressure on H. contortus for anthelmintic resistance. (+info)
Vaccination-induced protection of lambs against the parasitic nematode Haemonchus contortus correlates with high IgG antibody responses to the LDNF glycan antigen.
(8/57)
Lambs respond to vaccination against bacteria and viruses but have a poor immunological response to nematodes. Here we report that they are protected against the parasitic nematode Haemonchus contortus after vaccination with excretory/secretory (ES) glycoproteins using Alhydrogel as an adjuvant. Lambs immunized with ES in Alhydrogel and challenged with 300 L3 larvae/kg body weight had a reduction in cumulative egg output of 89% and an increased percentage protection of 54% compared with the adjuvant control group. Compared to the adjuvant dimethyl dioctadecyl ammonium bromide, Alhydrogel induced earlier onset and significantly higher ES- specific IgG, IgA, and IgE antibody responses. In all vaccinated groups a substantial proportion of the antibody response was directed against glycan epitopes, irrespective of the adjuvant used. In lambs vaccinated with ES in Alhydrogel but not in any other group a significant increase was found in antibody levels against the GalNAcbeta1,4 (Fucalpha1,3)GlcNAc (fucosylated LacdiNAc, LDNF) antigen, a carbohydrate antigen that is also involved in the host defense against the human parasite Schistosoma mansoni. In lambs the LDNF-specific response increased from the first immunization onward and was significantly higher in protected lambs. In addition, an isotype switch from LDNF-specific IgM to IgG was induced that correlated with protection. These data demonstrate that hyporesponsiveness of lambs to H. contortus can be overcome by vaccination with ES glycoproteins in a strong T-helper 2 type response-inducing aluminum adjuvant. This combination generated high and specific antiglycan antibody responses that may contribute to the vaccination-induced protection. (+info)