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PubMed2004

Molecular adaptation in the ice worm, Mesenchytraeus solifugus: divergence of energetic-associated genes.

The ice worm, Mesenchytraeus solifugus, is the largest glacially obligate metazoan and among only a few metazoan species that complete their life cycle at 0 degrees C. We conducted a large-scale sequencing analysis of cDNAs isolated from ice worm anterior segments. Sequence comparisons among an available group of ice worm, arthropod, chordate, and nematode homologues suggest that ice worms encode proteins that are less bulky, are less polar, and contain fewer charged residues. Also, subunits of the catalytic F1 ATP synthase complex appear to have diverged more rapidly than other ice worm genes examined, suggesting a role in cold-temperature adaptation. Modeling of F1 ATP synthase beta and gamma subunits identified nonconservative, ice worm-specific amino acid substitutions at subunit contact sites and at sites proximal to the catalytic site.

Amino Acid Sequence↗

PubMed2002

Murine filariasis: interleukin 4 and interleukin 5 lead to containment of different worm developmental stages.

We compared the impact of IL-4 and IL-5 deficiency during the fully permissive infection of BALB/c mice with the rodent filaria Litomosoides sigmodontis. IL-5, in contrast to IL-4, is crucial for the containment of adult worms during short- and long-term infections. IL-5 KO mice allowed development of more larvae into adult worms and showed up to 200 times more adult worms persisting during chronic infection (day 60 until 200 post-infection). This increased persistence was accompanied by a reduction in inflammatory nodules around adult filariae. In contrast, adult worm survival and nodule formation did not differ between BALB/c wild-type mice and BALB/c IL-4 KO or BALB/c IL-4 receptor (IL-4R) alpha-chain KO mice. In both IL-4 and IL-5 KO mice microfilaraemia was greatly enhanced (160-fold) and prolonged compared to wild-type mice. This extent of susceptibility to microfilariae required the presence of adult worms in a full infection cycle since upon intraperitoneal injection of microfilariae alone they were removed from BALB/c, BALB/c IL-4 KO and BALB/c IL-4R alpha-chain KO mice with equivalent kinetics, and since microfilarial survival was only slightly increased in IL-5 KO mice (factor of 5 vs. factor of 160 in full infection). In conclusion, IL-4 and IL-5 dependent effector pathways operate against different stages of filarial worms, and IL-5 has a greater impact on parasite containment than IL-4.

Animals↗

PubMed1997

Eosinophilia and intracranial worm recovery in interleukin-5 transgenic and interleukin-5 receptor alpha chain-knockout mice infected with Angiostrongylus cantonensis.

We infected interleukin-5 (IL-5)-transgenic (IL-5-Tg) and IL-5 receptor alpha knockout (IL-5R alpha -/-) mice with Angiostrongylus cantonensis to determine the possible roles of IL-5 and eosinophils in A. cantonensis infection in mice. IL-5-Tg mice demonstrated significantly higher eosinophilia in bone marrow, blood and cerebrospinal fluid (CSF), lower intracranial worm recovery and smaller female worms than naive C3H/HeN mice. Both IL-5-Tg and C3H/HeN mice evoked antigen-specific serum and CSF IgA antibody responses as early as days 5 and 7 postinfection, respectively. Prominent eosinophil infiltration was noted around intracranial worms in the subarachnoid spaces of the mouse brains; eosinophils adhering to the worm surface were degranulated. In contrast, IL-5R alpha -/- mice yielded a higher worm recovery than wild-type or heterozygous mice at day 20 postinfection and failed to provoke CSF eosinophilia. These findings indicate that A. cantonensis infection in the mouse causes IL-5 production and subsequent CSF eosinophilia, the latter probably being involved in the killing of intracranial worms.

Angiostrongylus cantonensis↗

PubMed1999

Schistosomal granuloma modulation. I. Schistosoma mansoni worm antigens CAA and CCA prime egg-antigen-induced hepatic granuloma formation.

Adult Schistosoma mansoni worms can positively modulate soluble egg antigen (SEA)-induced granulomas formed around SEA-coupled beads implanted in the liver. In this study, our aim was to further unravel the immunopathological characteristics of S.mansoni-worm-derived antigens in vivo. (a) Adult worm antigen (AWA)-coupled Sepharose beads, implanted into the liver, induced granulomas, containing numerous eosinophilic granulocytes and elicited marked periparticular fibrosis (composed of interstitial matrix proteins and basement membrane components). (b) Quantitative morphological analysis demonstrated that in naive mice, AWA-induced hepatic granuloma formation peaked in volume 16 days after injection of the beads. An accelerated response against AWA-coupled particles (peak volume at 8 days) was observed in mice carrying a single-sex, male S. mansoni infection. (c) When the granuloma volume induced by SEA-coupled beads in unisexually S. mansoni infected mice was compared to granulomas induced by beads laden with both SEA and AWA in unsensitized mice, no significant differences in granuloma volume were seen, indicating the existence of in vivo egg/worm antigen cross-sensitization. (d) Naive mice, sensitized with the worm antigens circulating anodic antigen (CAA) or circulating cathodic antigen (CCA), mounted a strongly accelerated response towards SEA-coupled beads implanted in the liver. We infer that, in vivo, worm antigens cross-sensitize with egg antigens and have both granulomogenic and fibrogenic characteristics. The S. mansoni soluble worm antigens CCA and CAA prime hepatic egg-antigen-induced granuloma formation possibly through the presence of immunogenic carbohydrates. These mechanisms lead to an accelerated response against SEA.

Animals↗

PubMed1990

Population dynamics of Trichostrongylus colubriformis in sheep: mathematical model of worm fecundity.

A mathematical model was constructed to predict the egg production of Trichostrongylus colubriformis worms as a function of worm age and host experience of infection. The model set egg production at zero until the worm was 14 days old, when a linear increase to maximum egg production levels occurred over 7 days. It was assumed that egg production remained at maximum levels until a threshold total worm burden was exceeded, when an exponential decline in egg production occurred. The rate of decline was assumed independent of worm age or worm burden. The estimated parameters (maximum egg production, threshold, lag and rate of decline) were optimized by fitting values predicted from the model to faecal egg counts observed in continuously infected sheep, giving R2 = 0.80. The model was validated against faecal egg counts obtained in two other continuous infection experiments, one performed at the same laboratory and the other in Britain.

Animals↗

PubMed1987

Monthly and seasonal fluctuations in abomasal nematode worm burden of naturally infected cattle in Austria.

From October 1980 until September 1981, 191 abomasa of naturally infected cattle were obtained from the slaughter-houses of Mürzhofen and Graz in the province of Styria, and of Wiener Neustadt in the province of Lower Austria and examined to study the monthly and seasonal occurrence of hypobiosis in Ostertagia ostertagi and Trichostrongylus axei. Infections in pastured animals (cows, steers and heifers) were compared with those in stabled animals (bulls fed on green forage and silage). Except for 10 bulls fed on silage all animals were parasitized. The results indicate that in Austria inhibited early fourth stage larvae of Ostertagia accumulate during the winter. Pastured animals showed a higher intensity of infection than stabled animals. Cows less than 3 and greater than 5 years of age had higher worm counts than those between these ages. There was a simultaneous accumulation of third stage larvae and adult worms of Trichostrongylus axei in autumn in steers and heifers. In bulls fed on green forage a higher adult worm burden was seen in winter. No significant correlation existed between the number of worm nodules in the abomasal mucosa and the various developmental stages of the worms. The count of in-utero immature eggs was higher in stabled than in pastured animals. No significant correlation between the number of in-utero eggs and that of female worms was noticeable. Numbers of mature Ostertagia eggs rose in spring, while in fall and winter the immature eggs predominated. An increase in the uterine egg count was observed in Trichostrongylus in autumn. Statistical analyses of our data show that the most decisive factor influencing the numbers of inhibited and adult Ostertagia as well as in-utero eggs is the system of animal management.

Abomasum↗

PubMed1988

Interactions between lungworms and gastrointestinal worms in calves.

Interactions between gastrointestinal worms (Ostertagia ostertagi, Cooperia oncophora) and lungworms (Dictyocaulus viviparus) in calves were studied by assessing the effect of primary infections with either group of worms on the development of homologous or heterologous challenge infections. Primary infections with lungworms resulted in some degree of resistance to challenge with gastrointestinal worms, but this resistance was lower than that found after homologous infection. Primary infections with gastrointestinal worms did not confer any resistance to challenge with lungworms. On the contrary, an indication was found of some enhancing effect of previous gastrointestinal worm infection on the establishment of lungworms. The highest degree of resistance against lungworm challenge was found where calves have been primarily infected with lungworms. Lungworm infections produced some elevation of serum pepsinogen levels. Gastrointestinal worms evoked a rise in circulating eosinophils, although this rise was smaller and occurred later than in lungworm-infected calves. Under the conditions of the experiment, the effect of 6000 infective lungworm larvae on weight gain was larger than the effect of 100,000 L3 of Ostertagia ostertagi and 100,000 L3 of Cooperia oncophora.

Animals↗

PubMed2004

Evaluation of techniques for the recovery of live intestinal Trichinella spiralis worms from experimentally infected foxes.

Previously described methods for the recovery of intestinal Trichinella worms from rodents are not feasible when applied in larger experimental animals such as foxes. In this study,worm recovery by standard technique of simple incubation of the intestine in saline was compared to embedment of the intestine in an agar gel. The small intestines of Trichinella spiralis infected foxes (4-5 days post inoculation) were slit lengthwise and the two corresponding halves were processed with one of the two incubation methods. Worms were recovered from all samples, and the total worm recovery ranged from 0.2-4.4% of the infection dose. The samples from the standard incubation were very unclear and time consuming to count compared with samples from the agar gel embedment,in which the intestinal debris were kept inside the agar. As the agar gel technique generally yielded higher numbers of worms than the corresponding standard incubation sample, it is with some optimisation, recommended for recovery of intestinal Trichinella worms from foxes.

Agar↗

PubMed2002

Strongyloides venezuelensis: longitudinal distribution of adult worms in the host intestine is influenced by mucosal sulfated carbohydrates.

Mechanisms for the longitudinal distribution of parasitic females of Strongyloides venezuelensis in the host intestine were investigated in mice. Adult worms were mostly recovered from the anterior-most one-third of the small intestine throughout the infection after infective larvae inoculation. Surgically implanted adult worms established well in the small intestinal mucosa, either in the duodenum or in the ileum, whereas a few worms could establish in the large intestine. Implanted worms in the small intestine remained where they were implanted until expelled. Mucosal mast cells were induced in the whole small intestine after the worm implantation. In the large intestine, a considerable number of adult worms settled in the mucosa of mutant mice, whose goblet cell mucins were undersulfated because of a mutation in sulfate-activating enzymes. In these mice, the degree of sulfation of goblet cell mucins in the large intestine was significantly reduced to the level of normal small intestine goblet cell mucins. Our results suggest that sulfated glycoconjugates, either from mucosal mast cells or goblet cells, have important effects on the longitudinal distribution of parasitic females of S. venezuelensis.

Animals↗

PubMedDate not supplied

Brugia pahangi and Wolbachia: the kinetics of bacteria elimination, worm viability, and host responses following tetracycline treatment.

Wolbachia spp., first reported from filariae nearly 30 years ago, have been suggested to contribute to the pathogenesis associated with human filarial infection. Tetracycline has been used to cure filariae of Wolbachia, as a novel means of chemotherapeutic treatment for both ocular and lymphatic filariasis. Tetracycline treatment of L4 or adult Brugia pahangi in vivo resulted in Wolbachia clearance. Less tetracycline was required to clear Wolbachia when treatment began at the L4 stage, compared with adults. Female worms died earlier than male worms when tetracycline was administered at the L4 stage. In all cases, Wolbachia clearance was closely associated with worm death. Worm recoveries decreased following the L4-L5 molt, suggesting tetracycline does not interrupt molting in this model system. Despite worm death and the assumed release of both bacterial- and worm-derived molecules, differences in inflammatory cell population and T cell cytokine mRNA profiles were negligible between tetracycline-treated and non-treated B. pahangi infected gerbils. These data suggest the contribution of Wolbachia to the in vivo induction of the gerbil immune response to B. pahangi may be small.

Animals↗

PubMed2001

Sequence analyses and comparative modeling of fly and worm fibroblast growth factor receptors indicate that the determinants for FGF and heparin binding are retained in evolution.

The presence of a large number of fibroblast growth factors (FGFs) and multiple splice forms of their receptors (FGFRs) in higher vertebrates makes the three-dimensional (3D) analysis of FGF interactions with their receptors a formidable task. The situation differs in Caenorhabditis elegans (worm) and Drosophila melanogaster (fruit fly), where only one or two FGF and FGFR sequences have been identified. Structural studies of the FGF-FGFR complexes in such primitive organisms should reveal the basic features of the ligand-receptor interactions as they first emerged through evolution. We have analysed the sequences of worm and fly FGFs and FGFRs and used the recently determined crystal structure of the human FGF1-FGFR2-heparin ternary complex [Pellegrini, L., Burke, D.F., von Delft, F., Mulloy, B. and Blundell, T.L. (2000) Nature 407, 1029-34] to construct 3D models of the homologous complexes. In spite of a low sequence similarity with their human counterparts, key structural features required for ligand-receptor and protein-heparin binding in humans are conserved in the fly and worm FGF-FGFR-heparin complexes. Analyses of the models show that tertiary interactions that are not conserved in sequence are maintained through novel interactions or complementary mutations in the fly and worm sequences. The overall charge distributions observed in the human FGF-FGFR-heparin complex are retained in the fly and worm models. The arginine residue at position 253 in the linker region between the Ig-like domains D2 and D3 in the wild type fly and worm sequences is particularly striking, as the Pro253Arg mutation in humans is responsible for Apert syndrome. This change may enhance the affinity of receptors for their FGF molecules as observed in Apert mutants.

Acrocephalosyndactylia↗

PubMed2002

Evidence for the presence of active cytochrome P450 systems in Schistosoma mansoni and Schistosoma haematobium adult worms.

Extracts of the adult worms of both Schistosoma mansoni and Schistosoma haematobium can metabolise some typical P450 substrates but to differing degrees. S. mansoni worm extracts displayed a approximately 12-fold higher specific activity for an aminopyrine substrate than rat liver microsomes. At 4 mM substrate concentration the demethylation reaction with N-nitrosodimethylamine (NDMA) (5 nmol HCHO/mg protein/min) was only half that of rat liver microsomes, whereas in extracts of S. haematobium, no detectable activity was found towards NDMA. Using ethylmorphine as substrate the demethylation activity of S. mansoni extracts (1.82 nmol HCHO/mg protein/min) was 5.5-fold lower than that of rat liver microsomes. Benzphetamine demethylase activity was also readily detectable in S. mansoni worm extracts at 6.79 nmol HCHO/mg protein/min compared with 10.20 nmol HCHO/mg protein/min in the case of rat liver microsomes. When aniline was used as substrate, surprisingly, no activity was found in worm extracts of either S. mansoni or S. haematobium, whereas rat liver microsomes showed high activity towards this amine. The anti-P450 2E1 and 2B1/2 cross-reacted with both worm homogenates and gave a specific band corresponding to a protein of molecular weight of approximately 50.0 kDa. A study with anti-P450 IVA antibody revealed that while this protein was strongly expressed in S. haematobium worm extracts, no immunoreactivity was observed with extracts of S. mansoni. Immunoblotting analyses with anti-P450 IIIA and P450 1A1 did not detect immunoreactive protein in either S. mansoni or S. haematobium.

Aminopyrine↗

PubMed1997

Immunization of mice with ultraviolet-attenuated cercariae of Schistosoma mansoni transiently reduces the fecundity of challenge worms.

In the present study cohorts of ICR and BALB/c mice were immunized with u.v.-irradiated cercariae of S. mansoni and challenged 5 weeks later, in parallel with unimmunized control mice, with approximately 100 cercariae. Total worm burdens at 5, 6, 7 and 8 weeks after challenge were significantly reduced by 27-65% in immunized mice. The total number of eggs and the number of eggs/female worm trapped in liver and small intestine were reduced significantly at 6 and 7 weeks post challenge in immunized, as compared to unimmunized mice. Decrease in tissue egg load could be achieved in BALB/c mice passively transferred with spleen cells from u.v.-attenuated cercaria-immunized mice. The proportion of female worms laying eggs in vitro was diminished only in worms recovered from highly resistant mice. The reduction in worm oviposition in immunized mice was no longer apparent at 8 weeks. The data taken together indicate that highly effective immunization of outbred and inbred mice with attenuated cercariae leads to significant, but transient, impairment in challenge worm egg production.

Adoptive Transfer↗

PubMed1998

Embryonation and infectivity of Ascaris suum eggs isolated from worms expelled by pigs treated with albendazole , pyrantel pamoate, ivermectin or piperazine dihydrochloride.

The effect of anthelmintic treatment of pigs on the embryonation and infectivity of Ascaris suum eggs isolated from expelled worms was investigated. Four groups of two naturally infected pigs were dosed with albendazole, pyrantel pamoate, ivermectin or piperazine dihydrochloride, respectively. Following worm expulsion, the eggs were removed from the uteri of female worms and embryonated in sulphuric acid. The infectivity of the embryonated eggs was tested through mouse inoculation. Egg development appeared normal in cultures from worms of the piperazine. pyrantel and ivermectin treated groups. In the albendazole cultures, egg development was largely arrested at the one-cell stage (81%). Where development occurred, irregular cell division was observed and only 7% of the eggs in the culture developed into fullgrown larvae. Following mouse inoculation with 2500 embryonated eggs, significantly lower lung larval counts on day 8 post inoculation (p.i.) were observed for mice in the piperazine and pyrantel treated groups (P < 0.01) compared to untreated controls. The larvae that developed in the eggs from ivermectin and albendazole treated groups appeared fully infective for mice. It was concluded that ovicidal activity of albendazole in vivo inhibits subsequent A. suum egg development in vitro; albendazole is, therefore, not suitable to obtain worms for egg embryonation to produce experimental inoculums. The anthelmintic treatment of pigs with ivermectin had only a limited effect on both embryonation and infectivity of A. suum eggs isolated from expelled worms.

Albendazole↗

PubMed1998

Production, faecal egg counts and worm burdens of ewe lambs which grazed six contrasting forages.

Lambs were grazed on monospecific swards of one of six forages, some containing condensed tannins (CT); sulla (Hedysarum coronarium), Lotus corniculatus and L. pedunculatus and some without CT (lucerne (Medicago sativa), plantain (Plantago lanceolata) and a ryegrass/white clover pasture (Lolium perenne/Trifolium repens)) to evaluate effects of forage type on gastrointestinal nematode burdens, faecal egg count as well as liveweight gain (LWG), wool growth and dag formation over a 42-day period. A new allotment of feed was provided at seven-day intervals, and feed was available ad libitum. Total worm burdens in a pre-treatment slaughter group were ca. 22000 of which ca. 5000 were in the abomasum. Within each forage type, 10 of the 25 lambs (NP) were given an anthelmintic drench at 14-day intervals and the remaining 15 lambs (P) were not drenched. Daily gains of the NP lambs were double that of P lambs which grazed either L. corniculatus, lucerne or pasture, but parasitism had a lesser effect on performance of lambs which grazed sulla and L. pedunculatus. Plantain was not palatable and all lambs performed poorly. Highest daily gains in P lambs were for those which grazed sulla (175 g/day) and L. pedunculatus (160 g/day) with total worm burdens of 13100 and 23000 for the respective treatment groups. The other forages resulted in lower daily LWG in P lambs, and performance was not related to either worm burdens or worm species. This experiment has shown that, when sulla is fed, there is a reduction in worm burdens and faecal egg count (FEC), but with Maku lotus which also contains CT, the good level of performance was achieved despite in high worm burdens and FEC. The mechanisms by which these forages enable high levels of productivity in the face of a parasitism appear to differ, but both could be incorporated into forage feeding systems to reduce dependence on anthelmintic drenches.

Abomasum↗

PubMed2003

Adult worms of the rodent intestinal nematode, Strongyloides venezuelensis, successfully invade chick intestinal mucosa.

In order to study the mucosal invasion of a rodent intestinal nematode in bird intestine, chicks were infected with the intestinal nematode of rodents, Strongyloides venezuelensis, by subcutaneous larva inoculation and adult worm implantation. No evidence was obtained for larvae reaching the lungs or the intestine after infective larva inoculation. Adult worms implanted in the small intestine invaded the mucosa and remained there at least for 24 h, whereas those implanted in the caecum were trapped by mucus, and did not invade the mucosa. Mucosal invasion of adult worms in the small intestine was confirmed by histological examination. The number of adult worms in the intestinal mucosal tissue dropped rapidly within the first 24 h, which was associated with infiltrating granulocytes around the worms. The present study suggests that S. venezuelensis adult worms are able to invade the intestinal tissue of chicks, which do not belong to the vertebrate class of its normal definitive host, but that they are eliminated rapidly by mucosal defense system of the bird.

Animals↗

PubMed1979

Transplantation of adult Trichinella spiralis between hosts: worm survival and immunological characteristics of the host--parasite relationship.

A technique for the transplantation of Trichinella spiralis worms directly into the host intestine is described. Infections established by the direct transfer of adult worms were essentially normal both in terms of their survival and reproduction and in their stimulation of, and susceptibility to, host immune responses. Worms transplanted from NIH mouse donors at intervals after infection had an equal ability to survive in the recipient, even when taken from the donor shortly before or during the process of worm expulsion, showing that expulsion does not require worms to be irreversibly damaged. It was noted, however, that after 7 days in the donor the ability of the worm to reproduce in the recipient was temporarily impaired.

Animals↗

PubMed1989

Schistosoma mansoni: evidence that 'non-permissiveness' in 129/Ola mice involves worm relocation and attrition in the lungs.

129/Ola mice resemble WEHI 129J mice in that around 70% of the individuals in any given population resist a primary infection with Schistosoma mansoni. Squashed-organ autoradiographic tracking of [75Se]selenomethionine-labelled parasites has shown that the kinetics of worm migration in 129/Ola mice follows the expected pattern, and that all rodents harbour essentially similar numbers of worms on day 14 post-infection. Combined lung and liver worm recovery techniques have revealed, however, that segregation of mice into 'permissive' and 'non-permissive' individuals can first be detected on day 20. 'Non-permissive' mice are characterized by the absence of schistosome eggs at all times in the liver parenchyma and, in consequence, lack the attendant manifestations of pathology; they do, however, harbour a few stunted worms in the liver and significant numbers of adult schistosomes in the pulmonary vasculature. Histological analysis of sectioned lung tissue from such animals indicates that some lung-located schistosomes feed, pair and lay eggs. Nevertheless, eosinophil-enriched inflammatory reactions develop around such worms and the parasites themselves exhibit various manifestations of trauma, ranging from minor vacuolation to gut herniation and extrusion. The phenomenon of 'non-permissiveness' thus involves retardation of worm development in the liver and, in consequence, relocation of the parasites to the lungs, where they become subject to host effector responses.

Animals↗