Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroi... more Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): parasite specific
Summary Mice exposed to primary infections with the parasitic intestinal nematode Nematospiroides... more Summary Mice exposed to primary infections with the parasitic intestinal nematode Nematospiroides dubius failed to show the mucosal mast cell (MMC) response which is characteristic of infections with other species of intestinal nematode and which was readily induced in these mice by infections with Nippostrongylus brasiliensis or Trichinella spiralis. The failure to generate a mucosal mastocytosis was independent of host strain or sex. When infections with N. dubius were established before, or concurrently with, T. spiralis or N. brasiliensis, the MMC response elicited by these species was delayed and/or depressed as was expulsion of the worms themselves. Infection with N. dubius given when a MMC response was already established, by exposure to T. spiralis, had no effect on MMC numbers. The possibility that the effects of N. dubius upon MMC responses reflect a lack of mastocytopoietic potential, rather than an active interference, was excluded by showing that SJL mice, which expel primary infections with N. dubius and express strong immunity to reinfection, developed marked mastocytosis during secondary infections. The depression of MMC responses by N. dubius is discussed in relation to the known immunosuppressive properties of this parasite and in relation to the T cell mediated control of MMC development.
There is limited information regarding responses by slow cycling stem cells during T. spiralis-in... more There is limited information regarding responses by slow cycling stem cells during T. spiralis-induced T-cell mediated intestinal inflammation and how such responses may relate to those of Paneth cells. Transgenic mice, in which doxycycline induces expression of histone 2B (H2B)-green fluorescent protein (GFP), were used. Following discontinuation of doxycycline ("chase" period), retention of H2B-GFP enabled the identification of slow cycling stem cells and long-lived Paneth cells. Inflammation in the small intestine (SI) was induced by oral administration of T. spiralis muscle larvae. Epithelial retention of H2B-GFP per crypt cell position (cp) was studied following immunohistochemistry and using the Score and Wincrypts program. Compared to non-infected controls, there was significant reduction in the number of H2B-GFP-retaining stem cells in T. spiralis-infected small intestines. H2B-GFP-retaining stem cells peaked at around cp 4 in control sections, but smaller peaks at higher cell positions (>10) were seen in sections of inflamed small intestines. In the latter, there was a significant increase in the total number of Paneth cells, with significant reduction in H2B-GFP-retaining Paneth cells, but a marked increase in unlabelled (H2B-GFP-negative) Paneth cells. In conclusion, following T. spiralis-infection, putative slow cycling stem cell numbers were reduced. A marked increase in newly generated Paneth cells at the crypt base led to higher cell positions of the remaining slow cycling stem cells.
The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by asse... more The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by assessing parasite survival following incubation with hydrogen peroxide and acetaldehyde/xanthine oxidase, generators of H2O2 and H2O2/O2(-), respectively. H. polygyrus worms could tolerate levels of < 0.25 mM hydrogen peroxide and < 0.5 mM/20 mU acetaldehyde/xanthine oxidase for 20 h, but, at higher concentrations, marked sex-dependent susceptibility was observed, with males being more sensitive to H2O2 and O2(-) than female worms. The ability to evade free radical-mediated damage was also evaluated by measuring superoxide dismutase (SOD) and catalase levels in worms isolated at different time points from four strains of mice with differing resistance phenotypes. Levels of both catalase and SOD in female worms isolated from 'rapid'[(SWRxSJL)F1], 'fast' (SWR) or 'intermediate' (BALB/c), but not 'slow' (C57BL/10), responder mice showed a strain-dependent increase with time. Moreover, male worms were rejected faster than female worms in the 'rapid',…
Helminth infections were studied in bank voles (Myodes glareolus) from 3 woodland sites in N.E. P... more Helminth infections were studied in bank voles (Myodes glareolus) from 3 woodland sites in N.E. Poland in the late summers of 1999 and 2002, to assess the temporal stability of derived statistics describing the regional helminth fauna and component community structure, and spatial influence on the latter. Regional helminth fauna changed dramatically between the two years, primarily due to a fall in the abundance of Syphacia petrusewiczi but was partially compensated for by an increase in Mesocestoides lineatus and Cladotaenia globifera. It was dominated by nematodes overall, but more so in 1999 than in 2002 when larval cestodes were more frequent. Most derived parameters for component community structure varied considerably between sites and the two surveys, the hierarchical order for sites not being maintained between surveys. They were susceptible to the disproportionate influence of three relatively rare, unpredictable species with the greatest overall aggregated distribution among hosts. Jaccard's similarity index was less influenced by the rare species, showing greater stability between sites and across years. In conclusion, temporal variation confounded any site-specific characteristics of the summary measures quantified in this study and their usefulness is therefore restricted to the years in which the surveys were conducted.
The relative importance of temporal and spatial effects was assessed in helminth communities of b... more The relative importance of temporal and spatial effects was assessed in helminth communities of bank voles (Myodes glareolus) in 3 woodland sites in N.E. Poland in the late summers of 1999 and 2002. Among common species the rank order of sites in relation to prevalence and abundance of infection was maintained between surveys. Site effects accounted for most of the deviance (in statistical models), and time was less important, so the exact location from which voles were sampled was of critical importance. The only exception was Syphacia petrusewiczi. In contrast, for derived measures such as species richness and diversity, most deviance was accounted for by host age, and the interaction between site and year was significant, implying that rank order of sites changed between years. Temporal effects on derived measures were generated primarily by a combination of relatively small changes in prevalence and abundance of the common, rather than the rare, species between the years of the study. In the medium-term, therefore, helminth communities of bank voles in N.E. Poland had a stable core, suggesting a substantial strong element of predictability.
The predictive power of the combined clinical tests is similar to the best values for magnetic re... more The predictive power of the combined clinical tests is similar to the best values for magnetic resonance imaging and ultrasonography. Moreover, the clinical tests are easy and convenient to do.
The version presented here may differ from the published version or from the version of record. I... more The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.
Prevalence and abundance of Cryptosporodium parvum and Giardia spp. were studied in 3 species of ... more Prevalence and abundance of Cryptosporodium parvum and Giardia spp. were studied in 3 species of rodents from forests and abandoned agricultural fields in N.E. Poland (Clethrionomys glareolus n l 459 ; Microtus arvalis n l 274 ; Apodemus flavicollis n l 209). Overall prevalence was consistently higher in the voles compared with A. flavicollis (70n6, 73n0 and 27n8 % respectively for C. parvum and 93n9, 96n3 and 48n3 % respectively for Giardia spp.). Prevalence and abundance of infection also varied markedly across 3 years with 1998 being a year of higher prevalence and abundance with both species. Fewer older animals (especially C. glareolus and M. arvalis) carried infection with C. parvum and infections in these animals were relatively milder. Although seasonal differences were significant, no consistent pattern of changes was apparent. Host sex did not influence prevalence or abundance of infection with C. parvum, but made a small contribution to a 4-way interaction (in 5-way ANOVA) with other factors in the case of Giardia spp. The 2 species co-occurred significantly and in animals carrying both parasites there was a highly significant positive correlation between abundance of infection with each, even with between-year, seasonal, host age, sex and species differences taken into account. Quantitative associations were confined to the 2 vole species in the study. These results are discussed in relation to the importance of wild rodents as reservoir hosts and sources of infection for local human communities.
Parasitic relationships, C.J.Barnard pathology and host behaviour, J.C.Holmes physiology alterati... more Parasitic relationships, C.J.Barnard pathology and host behaviour, J.C.Holmes physiology alteration during parasitism and their effects on host behaviour, S.N.Thompson opportunism in parasite life cycles, R.Tinsley a phylogenetic perspective on the evaluation of altered host behaviours - a critical look at the manipulation hypothesis, J.Moore parasites and host decision-making, M.Milinski parasites and the evolution of host sexual behaviour, A.Read human behaviour and the epidemiology of helminth infection - cultural practices and microepidemiology parasite transmission, G.S.Nelson human behaviour and the epidemiology of helminth infections - the role of behaviour in exposure to infection, D.A.P.Bundy the influence of host behaviour on some ectoparasites of birds and mammals, M.D.Murray.
The version presented here may differ from the published version or from the version of record. I... more The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.
Much interest has centred recently on the role of adaptive trade-offs between the immune system a... more Much interest has centred recently on the role of adaptive trade-offs between the immune system and other components of life history in determining resistance and parasite intensities among hosts. Steroid hormones, particularly glucocorticoids and sex steroids, provide a plausible mechanism for mediating such trade-offs. A basic assumption behind the hypothesis, however, is that steroid activity will generally correlate with reduced resistance and thus greater parasite intensities. Here, we present some findings from a field study of bank voles (Clethrionomys glareolus) in which we have looked at associations between parasite intensities, anatomical and morphometric measures relating to endocrine function and life history variation in three local populations inhabiting similar but mutually isolated woodland habitats. In general, sites with greater parasite intensities were those in which male C. glareolus had significantly larger adrenal glands, testes and seminal vesicles for their age and body size. Females also showed a site difference in adrenal gland weight. Some aspects of site-related parasite intensity were associated with asymmetry in adrenal gland weight and hind foot length, which may have reflected developmental effects on glucocorticoid activity.
Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 h... more Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 hypergammaglobulinaemia during the course of infection. In the present study, immune sera raised in CFLP mice by repeated infection contained 24 ng/ml IgG1 compared with a resting level of 2.4 mg/ml. IgG2a and IgG2b levels were depressed following infection from 1.5 to 0.6 mg/ml and 0.64 to 0.42 mg/ml respectively. IgM levels were unaltered by infection (0.16 mg/ml) whilst IgA levels increased from 0.7 to 1.2 mg/ml. Immunochemical fractionation of immune sera by a combination of affinity chromatography and gel filtration revealed that the anti-parasite activity of the original serum could be largely accounted for by purified IgG1 fractions as assessed by immunoprecipitin and immunofluorescence assays. Purified IgG1 was shown to react with antigenic components common to both adult homogenate and adult excretory-secretory antigen. In addition, absorption studies revealed that as much as 48% of purified IgG1 from immune serum reacted with adult N. dubius antigen. In vivo, IgG1 was the only purified immunoglobulin isotype to cause significant reduction in worm numbers in the gastrointestinal tract when administered alone, and to have any noticeable co-operative effect when administered in conjunction with immune mesenteric lymph node cells. IgG1 also caused severe stunting of worms, and promoted the adherence of peritoneal exudate cells to the worm surface in vitro. It is suggested that one mechanism by which immune mesenteric lymph-node cells exert their protective activity following cell transfer is by elevating IgG1 levels in recipient mice.
This paper reports the results of a genome-wide search for quantitative trait loci (QTL) influenc... more This paper reports the results of a genome-wide search for quantitative trait loci (QTL) influencing immunological responses to infection with the gastro-intestinal nematode parasite Heligmosomoides polygyrus in an F2 population created by crossing the resistant SWR and the susceptible CBA inbred mouse strains. Following infections, intestinal granuloma score at post mortem, mucosal mast cell protease 1, and IgE and IgG1 titres were recorded. The susceptible CBA mice had significantly higher IgG1, but significantly lower IgE, mucosal mast cell protease 1 and granuloma scores than SWR mice. Significant QTL were mapped to chromosomes 4, 11, 13 and 17 for granuloma score; chromosomes 12 and 17 for IgE; chromosome 10, 17 and 18 for IgG1 and chromosomes 1, 9, 10, 11, 17 and 18 for mucosal mast cell protease 1. Chromosomes 10, 11, 17 and 18 had QTL affecting more than one trait, and these are most likely to represent single QTL with multiple effects rather than multiple QTL. Some of these QTL map to regions known to harbour genes responsible for the induction of immunological responses to intestinal worms.
Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroi... more Immunological relationships during primary infection with Heligmosomoides polygyrus (Nematospiroides dubius): parasite specific
Summary Mice exposed to primary infections with the parasitic intestinal nematode Nematospiroides... more Summary Mice exposed to primary infections with the parasitic intestinal nematode Nematospiroides dubius failed to show the mucosal mast cell (MMC) response which is characteristic of infections with other species of intestinal nematode and which was readily induced in these mice by infections with Nippostrongylus brasiliensis or Trichinella spiralis. The failure to generate a mucosal mastocytosis was independent of host strain or sex. When infections with N. dubius were established before, or concurrently with, T. spiralis or N. brasiliensis, the MMC response elicited by these species was delayed and/or depressed as was expulsion of the worms themselves. Infection with N. dubius given when a MMC response was already established, by exposure to T. spiralis, had no effect on MMC numbers. The possibility that the effects of N. dubius upon MMC responses reflect a lack of mastocytopoietic potential, rather than an active interference, was excluded by showing that SJL mice, which expel primary infections with N. dubius and express strong immunity to reinfection, developed marked mastocytosis during secondary infections. The depression of MMC responses by N. dubius is discussed in relation to the known immunosuppressive properties of this parasite and in relation to the T cell mediated control of MMC development.
There is limited information regarding responses by slow cycling stem cells during T. spiralis-in... more There is limited information regarding responses by slow cycling stem cells during T. spiralis-induced T-cell mediated intestinal inflammation and how such responses may relate to those of Paneth cells. Transgenic mice, in which doxycycline induces expression of histone 2B (H2B)-green fluorescent protein (GFP), were used. Following discontinuation of doxycycline ("chase" period), retention of H2B-GFP enabled the identification of slow cycling stem cells and long-lived Paneth cells. Inflammation in the small intestine (SI) was induced by oral administration of T. spiralis muscle larvae. Epithelial retention of H2B-GFP per crypt cell position (cp) was studied following immunohistochemistry and using the Score and Wincrypts program. Compared to non-infected controls, there was significant reduction in the number of H2B-GFP-retaining stem cells in T. spiralis-infected small intestines. H2B-GFP-retaining stem cells peaked at around cp 4 in control sections, but smaller peaks at higher cell positions (>10) were seen in sections of inflamed small intestines. In the latter, there was a significant increase in the total number of Paneth cells, with significant reduction in H2B-GFP-retaining Paneth cells, but a marked increase in unlabelled (H2B-GFP-negative) Paneth cells. In conclusion, following T. spiralis-infection, putative slow cycling stem cell numbers were reduced. A marked increase in newly generated Paneth cells at the crypt base led to higher cell positions of the remaining slow cycling stem cells.
The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by asse... more The ability of oxygen radicals to kill Heligmosomoides polygyrus adult worms was examined by assessing parasite survival following incubation with hydrogen peroxide and acetaldehyde/xanthine oxidase, generators of H2O2 and H2O2/O2(-), respectively. H. polygyrus worms could tolerate levels of < 0.25 mM hydrogen peroxide and < 0.5 mM/20 mU acetaldehyde/xanthine oxidase for 20 h, but, at higher concentrations, marked sex-dependent susceptibility was observed, with males being more sensitive to H2O2 and O2(-) than female worms. The ability to evade free radical-mediated damage was also evaluated by measuring superoxide dismutase (SOD) and catalase levels in worms isolated at different time points from four strains of mice with differing resistance phenotypes. Levels of both catalase and SOD in female worms isolated from 'rapid'[(SWRxSJL)F1], 'fast' (SWR) or 'intermediate' (BALB/c), but not 'slow' (C57BL/10), responder mice showed a strain-dependent increase with time. Moreover, male worms were rejected faster than female worms in the 'rapid',…
Helminth infections were studied in bank voles (Myodes glareolus) from 3 woodland sites in N.E. P... more Helminth infections were studied in bank voles (Myodes glareolus) from 3 woodland sites in N.E. Poland in the late summers of 1999 and 2002, to assess the temporal stability of derived statistics describing the regional helminth fauna and component community structure, and spatial influence on the latter. Regional helminth fauna changed dramatically between the two years, primarily due to a fall in the abundance of Syphacia petrusewiczi but was partially compensated for by an increase in Mesocestoides lineatus and Cladotaenia globifera. It was dominated by nematodes overall, but more so in 1999 than in 2002 when larval cestodes were more frequent. Most derived parameters for component community structure varied considerably between sites and the two surveys, the hierarchical order for sites not being maintained between surveys. They were susceptible to the disproportionate influence of three relatively rare, unpredictable species with the greatest overall aggregated distribution among hosts. Jaccard's similarity index was less influenced by the rare species, showing greater stability between sites and across years. In conclusion, temporal variation confounded any site-specific characteristics of the summary measures quantified in this study and their usefulness is therefore restricted to the years in which the surveys were conducted.
The relative importance of temporal and spatial effects was assessed in helminth communities of b... more The relative importance of temporal and spatial effects was assessed in helminth communities of bank voles (Myodes glareolus) in 3 woodland sites in N.E. Poland in the late summers of 1999 and 2002. Among common species the rank order of sites in relation to prevalence and abundance of infection was maintained between surveys. Site effects accounted for most of the deviance (in statistical models), and time was less important, so the exact location from which voles were sampled was of critical importance. The only exception was Syphacia petrusewiczi. In contrast, for derived measures such as species richness and diversity, most deviance was accounted for by host age, and the interaction between site and year was significant, implying that rank order of sites changed between years. Temporal effects on derived measures were generated primarily by a combination of relatively small changes in prevalence and abundance of the common, rather than the rare, species between the years of the study. In the medium-term, therefore, helminth communities of bank voles in N.E. Poland had a stable core, suggesting a substantial strong element of predictability.
The predictive power of the combined clinical tests is similar to the best values for magnetic re... more The predictive power of the combined clinical tests is similar to the best values for magnetic resonance imaging and ultrasonography. Moreover, the clinical tests are easy and convenient to do.
The version presented here may differ from the published version or from the version of record. I... more The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.
Prevalence and abundance of Cryptosporodium parvum and Giardia spp. were studied in 3 species of ... more Prevalence and abundance of Cryptosporodium parvum and Giardia spp. were studied in 3 species of rodents from forests and abandoned agricultural fields in N.E. Poland (Clethrionomys glareolus n l 459 ; Microtus arvalis n l 274 ; Apodemus flavicollis n l 209). Overall prevalence was consistently higher in the voles compared with A. flavicollis (70n6, 73n0 and 27n8 % respectively for C. parvum and 93n9, 96n3 and 48n3 % respectively for Giardia spp.). Prevalence and abundance of infection also varied markedly across 3 years with 1998 being a year of higher prevalence and abundance with both species. Fewer older animals (especially C. glareolus and M. arvalis) carried infection with C. parvum and infections in these animals were relatively milder. Although seasonal differences were significant, no consistent pattern of changes was apparent. Host sex did not influence prevalence or abundance of infection with C. parvum, but made a small contribution to a 4-way interaction (in 5-way ANOVA) with other factors in the case of Giardia spp. The 2 species co-occurred significantly and in animals carrying both parasites there was a highly significant positive correlation between abundance of infection with each, even with between-year, seasonal, host age, sex and species differences taken into account. Quantitative associations were confined to the 2 vole species in the study. These results are discussed in relation to the importance of wild rodents as reservoir hosts and sources of infection for local human communities.
Parasitic relationships, C.J.Barnard pathology and host behaviour, J.C.Holmes physiology alterati... more Parasitic relationships, C.J.Barnard pathology and host behaviour, J.C.Holmes physiology alteration during parasitism and their effects on host behaviour, S.N.Thompson opportunism in parasite life cycles, R.Tinsley a phylogenetic perspective on the evaluation of altered host behaviours - a critical look at the manipulation hypothesis, J.Moore parasites and host decision-making, M.Milinski parasites and the evolution of host sexual behaviour, A.Read human behaviour and the epidemiology of helminth infection - cultural practices and microepidemiology parasite transmission, G.S.Nelson human behaviour and the epidemiology of helminth infections - the role of behaviour in exposure to infection, D.A.P.Bundy the influence of host behaviour on some ectoparasites of birds and mammals, M.D.Murray.
The version presented here may differ from the published version or from the version of record. I... more The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription.
Much interest has centred recently on the role of adaptive trade-offs between the immune system a... more Much interest has centred recently on the role of adaptive trade-offs between the immune system and other components of life history in determining resistance and parasite intensities among hosts. Steroid hormones, particularly glucocorticoids and sex steroids, provide a plausible mechanism for mediating such trade-offs. A basic assumption behind the hypothesis, however, is that steroid activity will generally correlate with reduced resistance and thus greater parasite intensities. Here, we present some findings from a field study of bank voles (Clethrionomys glareolus) in which we have looked at associations between parasite intensities, anatomical and morphometric measures relating to endocrine function and life history variation in three local populations inhabiting similar but mutually isolated woodland habitats. In general, sites with greater parasite intensities were those in which male C. glareolus had significantly larger adrenal glands, testes and seminal vesicles for their age and body size. Females also showed a site difference in adrenal gland weight. Some aspects of site-related parasite intensity were associated with asymmetry in adrenal gland weight and hind foot length, which may have reflected developmental effects on glucocorticoid activity.
Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 h... more Nematospiroides dubius, in common with many other species of metazoan parasite, induces an IgG1 hypergammaglobulinaemia during the course of infection. In the present study, immune sera raised in CFLP mice by repeated infection contained 24 ng/ml IgG1 compared with a resting level of 2.4 mg/ml. IgG2a and IgG2b levels were depressed following infection from 1.5 to 0.6 mg/ml and 0.64 to 0.42 mg/ml respectively. IgM levels were unaltered by infection (0.16 mg/ml) whilst IgA levels increased from 0.7 to 1.2 mg/ml. Immunochemical fractionation of immune sera by a combination of affinity chromatography and gel filtration revealed that the anti-parasite activity of the original serum could be largely accounted for by purified IgG1 fractions as assessed by immunoprecipitin and immunofluorescence assays. Purified IgG1 was shown to react with antigenic components common to both adult homogenate and adult excretory-secretory antigen. In addition, absorption studies revealed that as much as 48% of purified IgG1 from immune serum reacted with adult N. dubius antigen. In vivo, IgG1 was the only purified immunoglobulin isotype to cause significant reduction in worm numbers in the gastrointestinal tract when administered alone, and to have any noticeable co-operative effect when administered in conjunction with immune mesenteric lymph node cells. IgG1 also caused severe stunting of worms, and promoted the adherence of peritoneal exudate cells to the worm surface in vitro. It is suggested that one mechanism by which immune mesenteric lymph-node cells exert their protective activity following cell transfer is by elevating IgG1 levels in recipient mice.
This paper reports the results of a genome-wide search for quantitative trait loci (QTL) influenc... more This paper reports the results of a genome-wide search for quantitative trait loci (QTL) influencing immunological responses to infection with the gastro-intestinal nematode parasite Heligmosomoides polygyrus in an F2 population created by crossing the resistant SWR and the susceptible CBA inbred mouse strains. Following infections, intestinal granuloma score at post mortem, mucosal mast cell protease 1, and IgE and IgG1 titres were recorded. The susceptible CBA mice had significantly higher IgG1, but significantly lower IgE, mucosal mast cell protease 1 and granuloma scores than SWR mice. Significant QTL were mapped to chromosomes 4, 11, 13 and 17 for granuloma score; chromosomes 12 and 17 for IgE; chromosome 10, 17 and 18 for IgG1 and chromosomes 1, 9, 10, 11, 17 and 18 for mucosal mast cell protease 1. Chromosomes 10, 11, 17 and 18 had QTL affecting more than one trait, and these are most likely to represent single QTL with multiple effects rather than multiple QTL. Some of these QTL map to regions known to harbour genes responsible for the induction of immunological responses to intestinal worms.
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