The effects of single and combined dietary protein and zinc restrictions on the outcome of primary and challenge infections with the intestinal nematode Heligmosomoides polygyrus in mice were examined using a 3 x 2 factorial design that combined three levels of dietary protein (24% - control; 7% - marginal; 3% - low) with 2 levels of dietary zinc (60 mg/kg - control; 3 mg/kg - marginal). Protein and zinc restrictions, at these levels, produced independent effects on final worm burdens. While mice fed both marginal and low protein diets, and marginal zinc diets had significantly higher worm burdens in a primary infection, the response to a challenge infection was only impaired in animals fed the low protein diet. Eosinophilia was significantly reduced by zinc restriction in the primary infection and by the lowest level of protein restriction in the challenge infection. The magnitude of the serum IgG1 concentration was significantly lowered by protein restriction in both the primary and challenge infections. The impaired response to a challenge immunizing protocol in the animals fed the 3% protein diet, along with the reduced eosinophilia and IgG1 response, indicates a negative effect of protein deficiency on the host immune response to an intestinal nematode infection.

The objectives of this study were to determine the effect of different types and levels of dietary fiber on Heligmosomoides polygrus (Nematoda) in laboratory mice. BALB/c mice were randomly assigned to one of seven diets: no fiber, cellulose (5%, 10%, 20%), and pectin (5%, 10%, 20) and infected with H. polygyrus one week later. The length of intestine increased significantly with the concentration of pectin and was associated with longer villi, thicker mucosa and increased villus/crypt ratio. In contrast, changing concentration of cellulose had minimal effects on the gastrointestinal tract. More day 5 larvae were found in mice fed 20% pectin, but neither type nor level of dietary fiber affected worm survival or spatial distribution. An increase from 5% to 10% pectin increased per capita egg production both in vivo and in vitro, but a further increase to 20% pectin decreased per capita egg production in vivo to the low level seen in mice fed no fiber. However when the parasites from mice fed 20% pectin diet were cultured in vitro, they released very high numbers of eggs. Changing concentration of cellulose had no effect on parasite egg production in vivo or in vitro. Our study supports the hypothesis that pectin promotes the establishment and reproduction of Heligmosomoides polygyrus, and that this is closely related to the changes in gut morphology. Therefore we conclude that cellulose, not pectin, should be used to balance reduced content of macronutrients in studies on malnutrition and nematode infection.

The effect of low dietary zinc on the survival and reproduction of an intestinal nematode (Heligmosomoides polygyrus) during both primary (Experiment 1) and challenge (Experiment 2) infections was investigated. Plasma zinc concentrations were significantly lower in mice fed a 5 ppm zinc diet (ZR), compared with control mice fed a 60 ppm zinc diet (C) in both experiments. There were no significant differences between ZR and C mice in any other zinc parameter or on worm burdens or worm fecundity in either experiment. Comparisons between the primary infection and the challenge infection did suggest a possible effect of calorie restriction on worm burdens. / Parasitic infection did, however, affect the host nutritional status. Spleen weight was significantly higher in infected mice in both experiments. In the challenge infection, both liver and spleen copper concentrations were significantly higher, and spleen iron concentration significantly lower in the infected mice. That these significant results were seen only in the challenge infection may suggest the role of the host immune response.

Protein deficiency may increase susceptibility to gastrointestinal (GI) parasitic infections, possibly as a result of impaired systemic and/or intestinal effector responses induced by downregulation of Th2 cytokines and/or upregulation of Th1 cytokines. To test this hypothesis, female BALB/c mice (n = 18/diet) were fed a control (24%), marginal (7%), or deficient (3%) protein diet and given a challenge infection with the GI nematode, Heligmosomoides polygyrus. The 3% mice had higher worm burdens at 1, 2 and 4 weeks post-challenge infection (pci), lower increases in serum IgE, reduced intestinal eosinophilia, and depressed mucosal mast cell proliferation and activation at 1 to 2 weeks pci. To determine whether these suppressed effector responses in the 3% mice were associated with altered spleen and mesenteric lymph node (MLN) cytokine profiles, cells were restimulated in vitro with parasite antigen and cytokine concentrations were measured. Deficient MLN cells secreted significantly less IL-4 and more IFN-gamma at 1--2 weeks pci than did control MLN cells. Deficient spleen cells also secreted more IFN-gamma at 2 weeks pci compared with control spleen cells. From RT-PCR analyses, the 3% mice also had lower IL-4 mRNA expression in spleen and MLN at 1--2 weeks pci. Our study supports the hypothesis that protein deficiency exacerbates the survival of a GI nematode parasite by decreasing IL-4 (Th2) and increasing IFN-gamma (Th1) early in the infection, leading to reduced gut and systemic Th2 effector responses.

Association between albendazole anthelmintic resistance and a panel of life history traits in Heligmosomoides polygyrus was investigated both prior to and during drug-selection. Associations prior to anthelmintic application were studied in ten independent lines isolated without drug treatment from a susceptible stock population by random genetic drift. Variation among lines was detected in several life history traits (i.e., establishment, development and survival), and, despite lack of previous exposure to albendazole, lines also varied in their tolerance to the drug. No significant correlations were detected between drug-tolerance and any of the life history traits after 11 generations of isolation. The apparent lack of fitness differential between lesser and more drug-tolerant individuals of the susceptible population is not in accordance with the assumption that the low frequency of drug tolerant individuals in the susceptible population is explained by their lower fitness, but is consistent with the neutral theory. Associations between life history traits and drug resistance were also studied using two lines selected for albendazole resistance from the stock population, and two control lines exposed to the same monthly passage procedure but not to the drug. After 10 generations of selection, drug resistance increased from an LC50 of 0.48 $ mu$M to 2.03 $ mu$M. In a primary infection, the higher establishment and higher worm numbers one-month post-infection in the resistant parasites compared to the stock parasites occurred only in the drug-selected lines. Changes in these traits were attributed to the drug selection regime. In contrast, both drug-selected lines and passaged lines showed a faster rate of development and higher early egg production compared with the stock parasites; these changes were attributed to the passage procedure that presumably acted as a selective force on early life history traits. In immunized hosts, changes in several traits that o

The influence of energy restriction on the transmission dynamics of a direct life cycle nematode, Heligmosomoides polygyrus, within free-running arena Systems has to date remained unexplored. Indoor populations of CD-1 outbred mice were established for 12 weeks in arenas and fed either energy-suffi ci ent (ES) or energy-restricted (ER-20% réduction in metabolizable energy) diets. Infection was introduced to ail arenas following 3 weeks of diet treatment. Contrary to previous findings, the mice fed the ER diets compensated for the deficiency by increasing food consumption and thus, while early in the experiment energy restriction was evident, dietary effects were no longer observed after 6 weeks. Worm burdens, measured at 4 time points over the course of the experiment, were higher in mice fed the ES diets. Although mice fed the ER diets had greater contact with infected areas, the mice fed the ES diets increased the duration of behaviours that heighten ingestion of the parasite - self and allogrooming. Dietary effects on behaviour were observed only after infection was introduced and were more pronounced in the durations of individual bouts rather than in overall durations or time budgets. Nesting bouts were prolonged in mice in the ER arenas perhaps as a means of thermoregulation to counteract the combined effects of infection and energy restriction. The duration of exploratory bouts was also higher in the ER mice possibly due to an inability to receive or process information in their environment. Social interactions, predominantly involving sniffing, increased after infection was introduced, supporting the rôle of odour in communicating infection status in same-sex conspecifics. Together these results provide a more comprehensive ethogram of mice in a semi-natural setting and highlight those behaviours where adaptive plasticity allows response to dietary and infection stresses.

Interactions among zinc deficiency, energy restriction, immunity and Heligmosomoides polygyrus (Nematoda) infection in mice were investigated. Mice were fed zinc-sufficient (Zn+: 60mg zinc/kg diet), zinc-deficient (Zn$-$: 0.75 mg/kg) or pair-fed (PF) diets. Liver and serum zinc concentrations were reduced in Zn$-$ mice, but zinc content of worms was unaffected by host diet. Both zinc deficiency and energy restriction accelerated worm maturation during a primary infection, but zinc deficiency caused stunting of female worms. Energy restriction led to a anteriorad distribution of worms along the intestine whereas zinc deficiency led to a posteriorad distribution. Enhanced parasite survival in Zn$-$ and PF mice was associated with a decreased immune response in both primary and challenge infections. In the primary infection, spleen cell production of interleukin-4 (IL-4) and interferon-gamma (IFN-$ gamma$), peripheral eosinophilia and serum levels of IgE and IgG1 were reduced by zinc deficiency, whereas the reduced delayed type hypersensitivity (DTH) response and impaired interleukin-5 (IL-5) production were attributed to energy restriction. In the challenge infection, reduced antibody levels (total IgE and IgG1, parasite-specific IgG1 and IgG3) and eosinophilia were attributed to zinc deficiency whereas the higher worm numbers were attributed to a combined effect of zinc deficiency and energy restriction. Although the absolute number of spleen cells was reduced in both Zn$-$ and PF mice, neither deficiency altered the proportion of the cell subpopulations. In vitro functional assays in response to parasite antigen (Ag) revealed that T cell proliferation was reduced by a direct effect of zinc deficiency on T cells, and by the effects of energy restriction on antigen presenting cells (APC). Impaired cytokine production in Zn$-$ mice was more complex. Zinc deficiency reduced T cell function (IL-4 production), energy restriction decreased T cell (IFN-$ gamma$ productio

Both major histocompatibility genes (MHC) and infection have been shown to influence urinary odours in mice, and mice may use MHC-associated odours to detect kin for the purpose of choosing communal nesting partners, or to avoid mating with close relatives. Additionally, mice may use infection-related odours to avoid mating with sick individuals or those genetically susceptible to infection. I tested the above theories using urine as the source of odour. In a series of odour preference experiments, employing two MHC-congenic strains of mice (B10 and B10.Q), I tested the proposition that females prefer MHC-similar female odours when choosing female relatives as nesting partners, and that females prefer MHC-disparate male odours for the purpose of disassoratative mating. I found that females did not display a preference for MHC-similar female odours or MHC-disparate male odours. However, when B10.Q male urine donors were infected with 100 L3 larvae of Heligmosomoides polygyrus (Nematoda), both strains of female displayed a significant preference for the odours of uninfected B10 males. To determine whether female odour preference for uninfected males extended to actual mate choice, I subsequently examined female mate choice in a controlled setting. Using CD-1 outbred mice, I found that females preferred to mate with uninfected males over males subclinically infected with 200 L3 of H. polygyrus , as evidenced by first ejaculation preferences. In this experiment, males were tethered, and as such, male dominance interactions were prevented. Thus, in the final experiment, to assess whether male dominance interactions influenced female mate choice, in addition to infection, I tested female mate choice in a seminatural setting, which allowed for social interactions to occur. In this study, paternity was ascertained through DNA analysis and the resulting data indicated that neither male dominance status nor infection had a substantial impact on fema / Overall, the data do not support the theory that MHC-based preferences occur through urinary odours. However, the results do substantiate previous findings regarding female preferences for the odours of uninfected males. Furthermore, data from the controlled mate choice assay indicate that female odour preference for uninfected males extends to actual mate choice. Conversely, in the seminatural setting neither dominance nor infection prevailed as factors driving female mate choice. I suggest that this may be a consequence of the structural complexity of my arenas.

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