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PubMed2001

A Brugia malayi homolog of macrophage migration inhibitory factor reveals an important link between macrophages and eosinophil recruitment during nematode infection.

Infections with the helminth parasite Brugia malayi share many key features with Th2-mediated allergic diseases, including recruitment of eosinophils. We have investigated the dynamics of inflammatory cell recruitment under type 2 cytokine conditions in mice infected with B. malayi. Among the cells recruited to the site of infection is a novel population of "alternatively activated" macrophages that ablate cell proliferation and enhance Th2 differentiation. By profiling gene expression in this macrophage population, we found a dramatic up-regulation of a recently described eosinophil chemotactic factor, eosinophil chemotactic factor-L/Ym1, representing over 9% of clones randomly selected from a cDNA library. Because B. malayi is known to secrete homologs (Bm macrophage migration inhibitory factor (MIF)-1 and -2) of the human cytokine MIF, we chose to investigate the role this cytokine mimic may play in the development of the novel macrophage phenotype observed during infection. Strikingly, administration of soluble recombinant Bm-MIF-1 was able to reproduce the effects of live parasites, leading both to the up-regulation of Ym1 by macrophages and a marked recruitment of eosinophils in vivo. Because activity of Bm-MIF-1 is dependent upon an amino-terminal proline, this residue was mutated to glycine; the resultant recombinant (Bm-MIF-1G) was unable to induce Ym1 transcription in macrophages or to mediate the recruitment of eosinophils. These data suggest that macrophages may provide a crucial link between helminth parasites, their active cytokine mimics, and the recruitment of eosinophils in infection.

Animals↗
PubMed2003

dnaA gene sequences from Wolbachia pipientis support subdivision into supergroups and provide no evidence for recombination in the lineages infecting nematodes.

Wolbachia pipientis is an intracellular bacterial endosymbiont of arthropods and filarial nematodes. Six main supergroups of W. pipientis have been described: supergroups A, B, E, and F encompass arthropod wolbachiae; supergroups C and D encompass nematode wolbachiae. The description of these six supergroups has been based on the analysis of only two genes (ftsZ and 16S rDNA) and before decisions are taken on the taxonomic status of the six supergroups, analysis of further genes is required. In addition, the branching order of the six supergroups is still unresolved. Sequence information from other genes is also needed to allow phylogenesis to be addressed through the analysis of a higher number of characters. Here we report sequences from a portion of the gene coding for the DNAA protein of W pipientis, generated from the endosymbionts of 22 host species. Phylogenies based on dnaA gene sequences are congruent with the existence of at least six supergroups of W pipientis. In addition, subtrees generated for nematode wolbachiae in supergroups C and D were compared to the trees based on the already available gene sequences (ftsZ, 16S rDNA and wsp). The congruence observed among the trees based on the different genes agrees with the hypothesis that recombination does not occur in nematode wolbachiae.

Animals↗
PubMed1990

Effects of ivermectin and fenbendazole in strategic treatment of gastrointestinal nematode infections in cattle.

Four groups of 18 beef calves each were used to evaluate effects of different treatments on parasite control and weight gains. The investigation extended from November 1986 (weaning) to October 1987. Group-1 calves were treated with ivermectin (200 micrograms/kg of body weight, SC) at approximately 6-week intervals for a total of 8 treatments; group-2 calves were given the same dosage of ivermectin by the same route of administration as group-1 calves in November, March, and July; group-3 calves were given fenbendazole paste (5 mg/kg, PO) at the same times as group-2 calves; and group-4 calves served as untreated controls with provision for ivermectin salvage treatment. All groups grazed on individual pairs of larval-contaminated, 1.6-ha pastures. Highest (P less than 0.05) initial worm counts in fall tracer calves were found in group 3 (Ostertagia ostertagi and Trichostrongylus axei adults) and group 4 (O ostertagi and Haemonchus adults). Fecal egg counts of group-1 calves were low throughout the experiment and pasture larval counts remained negligible after July. Egg counts and larval counts of other groups remained higher into summer. Worm counts, including O ostertagi inhibited early fourth-stage larvae (EL4), were highest (P less than 0.05) in groups-3 and -4 spring tracer calves; numbers of O ostertagi EL4 were similarly high in groups 2, 3, and 4; and T axei counts were highest (P less than 0.05) in groups-3 and -4 yearlings slaughtered in spring. Liveweights of group-1 calves were greater (P less than 0.05) than in other groups from March 2 to October, and by July 2, group-2 calves had a liveweight advantage over group-4 calves. Group-3 calves had the lowest rate of gain from March to July and mean liveweight of the group was less (P less than 0.05) than in all other groups from April to October. Only minimal worm numbers were recovered from groups-1 or -2 calves in October. Large numbers of O ostertagi and T axei were recovered from group-4 calves and O ostertagi from group-3 calves. A few calves in groups 3 and 4, but particularly in group 4, were affected by type-II disease (chronic to acute gastritis caused by maturation and emergence of previously inhibited larvae) from August to October. Final mean liveweights in descending order were 365 kg in group 1, 328 kg in group 2, 316 kg in group 4, and 281 kg in group 3.

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PubMed1984

Effect of size of Trichinella spiralis (Nematode) infections on glucose and ion transport in the rat intestine.

An in vivo perfusion technique, using 3 intestinal loops representing the anterior, mid and posterior regions of the rat small intestine, was used to determine intestinal glucose uptake 5 days after infection with Trichinella spiralis. At high levels of infection (3,000 and 6,000 larvae/rat) net glucose absorption by the intestinal mucosa was significantly impaired in all regions of the small intestine when compared to uninfected controls. At low levels of infection (50 larvae/rat) glucose uptake by the mucosa was significantly enhanced in all 3 regions of the small intestine. Intermediate levels of infections (200-1,000 larvae/rat) also enhanced glucose uptake, but only in the anterior regions of the small intestine. When washings from the small intestine of rats infected with 50 larvae/rat were added to the perfusion fluid used on uninfected rats, glucose uptake was also significantly enhanced. These results suggest that at low levels of infection the intestinal lumen contains a metabolite which may affect the mucosal transport of glucose and the related fluxes of H2O, Na+, Cl-, and K+, in the rat intestine. Luminal [H+] and pCO2 decreased from the proximal to distal regions of the small intestine following perfusion; pO2 was significantly decreased in the proximal and distal regions.

Animals↗
PubMed1983

Cortisone-induced immunotolerance to nematode infection in CBA/Ca mice. II. A model for human chronic trichuriasis.

Treatment of CBA/Ca mice with cortisone acetate for a short period after infection with Trichuris muris induces a state of immunotolerance which allows the development and survival of a chronic infection. Mice harbouring such infections were found to be less capable of responding to a primary infection with Trichinella spiralis or of producing humoral responses to lipopolysaccharide and sheep red blood cells. Mesenteric lymph node T cells, however, were as responsive to the polyclonal activator phytohaemagglutinin as those from normal mice. Homing to the intestinal tract of activated mesenteric lymph node cells from helminth-infected donors was not impaired in the animals harbouring chronic infections. The results are discussed in terms of antigenic competition and with respect to their relevance to chronic human trichuriasis.

Animals↗
PubMed1982

Population build up of gastrointestinal nematode infections in ewes and lambs on pasture grazed by calves in the previous year.

The development of trichostrongylid infections was studied in ewes, lambs and tracer lambs grazing a pasture which has been used by calves in the previous year. Treatment with fenbendazole of the ewes two days before they were turned out to pasture virtually prevented infections with trichostrongylid species characteristic for sheep. Significant burdens of Ostertagia leptospicularis, Cooperia oncophora and Nematodirus helvetianus were found. An increased pasture infectivity level compared to spring was observed in C oncophora and O leptospicularis in August and September. The possibility that O leptospicularis may build up to pathogenic levels in sheep and cattle as a result of alternate grazing is discussed. The two other species are probably of little significance as pathogens in sheep.

Animals↗
PubMed1993

[The serological diagnosis of gastrointestinal nematode infections in cattle].

Ostertagia ostertagi and Cooperia oncophora are widely distributed and are the most important parasites affecting young bovine livestock. Therefore, there is a substantial need for sensitive and specific parameters in support of their diagnosis, especially for sub-clinical disease correlated to production loss. In this review, the value and the application as a diagnostic tool of pepsinogen, gastrin and antibody response are discussed. An increase in pepsinogen or gastrin reflects mucosal damage caused by an Ostertagia infection. Some controversy exists about the level of pepsinogen and gastrin, which may be considered indicative for the diagnosis of clinical and sub-clinical ostertagiasis. Pepsinogen levels between 3,000 tot 4,000 mU tyrosine are regarded indicative for subclinical disease, values in excess of 5,000 mU tyrosine are considered significant for diagnosing clinical disease. For gastrin, it is suggested that based on group means, values of 400 pg/ml are indicative for subclinical parasitic disease in calves with reduced daily weight gain, while threshold levels of > or = 1000 pg/ml gastrin are representative for clinical ostertagiasis. Antibody responses to Ostertagia and Cooperia can be assessed using the enzyme immunoassay (EIA). Until now, mainly crude worm extracts have been used as antigen source in the EIA. They are not species-specific as discussed experiments provide evidence of a close relationship between the onset of parasitic disease and the evolution of the group mean parameters. However, data demonstrate serious variations between animals, which impede a reliable individual diagnosis. For longitudinal epidemiological studies especially pepsinogen and gastrin have proven their value, exhibiting fast fluctuations induced by infection or as a result of treatment. Conversely antibody levels were found to be more stable and therefore are useful in large cross-sectional studies, enabling a rough assessment of the degree of infection.

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PubMed1997

Mast cell heterogeneity in the gastrointestinal tract: variable expression of mouse mast cell protease-1 (mMCP-1) in intraepithelial mucosal mast cells in nematode-infected and normal BALB/c mice.

Soluble granule chymases in rodent intestinal mucosal mast cells (IMMCs) may play an important role in altering epithelial permeability during immediate hypersensitivity reactions. Using a monoclonal antibody against the chymase mouse mast cell protease-1 (mMCP-1), we have shown that it is constitutively expressed in < or = 20% of esterase-positive (esterase+) IMMCs but not in esterase+ gastric mucosal mast cells (GMMCs) in normal BALB/c mice. Intestinal infection with mouse- or rat-adapted strains of Nippostrongylus brasiliensis resulted in IMMC hyperplasia with 100% of esterase+ IMMCs expressing mMCP-1. In contrast, there was a variable response in terms of numbers of GMMCs and of the proportion expressing mMCP-1. Esterase+ mast cells in the gastric submucosa, muscularis, ear pinna, lung parenchyma, major airway submucosa, and peritoneal cavity did not express mMCP-1. The few airway esterase+ mast cells expressing mMCP-1 were, like the great majority of IMMCs and GMMCs, located intraepithelially. In conclusion, mMCP-1 is predominantly expressed by intraepithelial mucosal mast cells but not in all sites; the immunological stimulus associated with intestinal nematodiasis substantially up-regulates mMCP-1 expression by mast cells in the jejunum but not in the stomach; IMMCs and GMMCs in BALB/c mice are phenotypically and possibly functionally distinct.

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