Biological and immunological aspects of the host-parasite relationship were examined in mice which are susceptible (A/J) and resistant (B10.A) to Giardia muris. B10.A exhibited a shorter latent period, lower cyst output during the acute phase of the infection and shorter period of cyst release compared to A/J. Characteristics of the infection transmitted from mouse-to-mouse and those induced by oral inoculation with cysts or trophozoites were similar. The infection was longer in male A/J and B10.A mice compared to females. Susceptibility and resistance during both the acute and elimination phases of the infection were under non-H-2-linked multigenic control. A/J and B10.A differed in non-specific serum IgG and IgA, but not in the specific IgG and IgA to G. muris. Specific antibodies participated in complement-mediated killing of trophozoites. Spleen, mesenteric lymph node and peritoneal cells from A/J and B10.A mice had a similar ability to kill trophozoites. The capacity of B10.A to mount inflammatory responses was greater than that of A/J. A/J were more immunosuppressed than B10.A during the infection, particularly at mucosal sites. Macrophage-like suppressor cells were shown to be the mediators of this suppression.

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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