Taenia crassiceps: experimental model of intraocular cysticercosis

An experimental model of Taenia crassiceps intraocular cysticercosis was developed in rabbits. The objectives of this study were to analyze the pathophysiology of this parasitic infection and to evaluate the humoral immune response. Cysticerci, inoculated in the anterior chamber of the eye, were able to grow; no inflammatory changes in the eye or anticysticercus antibodies in serum or in aqueous humor were detected during the 12-day period. In contrast, rabbits that had previously been either infected intraperitoneally with living T. crassiceps cysts or immunized intramuscularly with T. crassiceps antigenic extract developed an intense inflammatory reaction in the eye and high levels of antibodies were detected in serum and aqueous humor even before the intraocular inoculation of parasites. Furthermore, intraocular cysticerci showed minimal growth and some were eliminated. These findings support the concept that the eye is an immunologically privileged site in the nonimmunized host and the importance of the immune response in the elimination of this parasitic infection.     

Taenia crassiceps cysticercosis: protective effect and immune response elicited by DNA immunization

The nucleotide sequence of a protective recombinant antigen of Taenia crassiceps cysticerci present in all stages of Taenia solium (KETc7), cloned into pcDNA3 plasmid with the signal peptide sequence of the beta-glycan receptor (pTc-sp7), has been shown to be effective in protecting mice against experimental infection of T. crassiceps. To explore further the possibilities of this form of immunization and the immune response induced, mice were injected intramuscularly (i.m.) or intradermally (i.d.) with 3 doses of pTc-sp7. Similar levels of resistance were found using either i.m. or i.d. immunization. Spleen cells from i.d. and i.m. DNA immunized mice induced a specific T-cell response to T. crassiceps antigens and to a synthetic peptide from the immunogen itself (GK-1). Proliferated cells were especially enriched in CD8+ CD4- T-lymphocytes. A clear increase in the percentage of CD3+ cells that produce gamma-interferon and interleukin-2 was detected when measuring the intracellular cytokine production, an indication of the pTc-sp7 capacity to induce an effective cellular response. These results provide encouraging information on the use of KETc7 in the prevention of cysticercosis as well as a first insight into the characterization of the immune response induced by pTc-sp7 that hints to the relevance of cellular immunity in protection.     

Effect of oral zinc supplementation upon Taenia crassiceps murine cysticercosis.

The effect of zinc supplementation on Taenia crassiceps murine cysticercosis was studied in susceptible BALB/cAnN mice. Female offspring of mice supplemented with high zinc throughout gestation and lactation were intraperitoneally infected with T. crassiceps cysticerci. Offspring from nonsupplemented mothers were used as controls. Significantly fewer parasites were recovered from zinc-supplemented mice (Zsm) 30 days after infection. Increased resistance was not related to the IgG antibody response. At early stages of infection, T cells from Zsm proliferated to T. crassiceps antigens, whereas cells from control mice did not respond. Infection caused in both groups a decrease in CD3+ cell percentages, which was more pronounced in the controls, and paralleled by a decrease in CD8+ cells; CD3+ and CD8+ percentages returned to normal levels at later stages of infection. In contrast, the CD4+ subpopulation only decreased in control mice. Intracellular cytokine determinations indicate that zinc supplementation favored a stronger and persistent type-1 T cell response in cysticerci-infected mice, which probably participates in the observed increased resistance.     

Tissue damage in the male murine reproductive system during experimental Taenia crassiceps cysticercosis

Chronic infection with Taenia crassiceps cysticerci in male mice increases the level of estradiol in serum, whereas it reduces that of testosterone. In addition, male mice lose their typical male reproductive behavior. The effects of cysticerci infection on the histomorphology of male reproductive tissues are unknown. The present study was undertaken to determine the histological changes in testes, seminal vesicles, and prostate of male mice infected with T. crassiceps cysticerci. At 16 wk of infection, all tissues exhibited high inflammatory infiltrate. Tissue lesions included marked dilation and peripheral fibrosis. In the testes, a diminution of spermiogenesis was observed. The overall results indicated that the histological changes in chronically parasitized male mice occurred with changes in hormone levels, simultaneously with the high inflammatory immune response.     

Taenia crassiceps: androgen reconstitution of the host leads to protection during cysticercosis

The effects of testosterone, dihydrotestosterone, and 17beta-estradiol in castrated mice of both sexes infected with Taenia crassiceps cysticerci were studied. The results showed that castration and treatment with either testosterone or dihydrotestosterone before infection decreased parasite loads by 50 and 70%, respectively, while the treatment with 17beta-estradiol increased it by three times in both genders, as compared with control mice. The specific splenocyte cell proliferation and IL-2 and IFN-gamma production were depressed in infected-castrated mice of both genders, while treatment with testosterone or dihydrotestosterone produced a significant proliferation recovery and enhanced production of IL-2 and IFN-gamma. On the other hand, the humoral response was unaffected with testosterone or dihydrotestosterone restitution, while the treatment with estradiol in both genders augmented the levels of anti-cysticerci IgG, as well as IL-6 and IL-10 production. These results suggest a protective role for androgens, possibly through the stimulation of the specific cellular immunity.     

Identification of loci controlling restriction of parasite growth in experimental Taenia crassiceps cysticercosis

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps.     

Protective immunity against Taenia crassiceps murine cysticercosis induced by DNA vaccination with a Taenia saginata tegument antigen

This study investigated the protective capacity of the recombinant Taenia saginata Tso18 antigen administered as a DNA vaccine in the Taenia crassiceps murine model of cysticercosis. This Tso18 DNA sequence, isolated from a T. saginata oncosphere cDNA library, has homologies with Taenia solium and Echinococcus sp. It was cloned in the pcDNA3.1 plasmid and injected once intramuscularly into mice. Compared to saline-vaccinated control mice, immunization reduced the parasite burden by 57.3-81.4%, while lower levels of non-specific protection were induced in control mice injected with the plasmid pcDNA3.1 (18.8-33.1%) or a plasmid with irrelevant construct, pcDNA3.1/3D15 (33.4-38.8%). Importantly, significant levels of protection were observed between the pcDNA3.1/Tso18 plasmid and pcDNA3.1/3D15 plasmid immunized mice. Mice immunized with pTso18 synthesized low levels of, primarily IgG1 sub-class, antibodies. These antibodies were shown to recognize a 66 kDa antigen fraction of T. crassiceps and T. solium. Splenocytes enriched in both CD4+CD8- and CD4-CD8+ T cells from these vaccinated mice proliferated in vitro when exposed to antigens from both T. solium and T. crassiceps cestodes. Immunolocalization studies revealed the Tso18 antigen in oncospheres of T. saginata and T. solium, in the adult tapeworm and in the tegument of T. solium cysticerci. The protective capacity of this antigen and its extensive distribution in different stages, species and genera of cestodes points to the potential of Tso18 antigen for the possible design of a vaccine against cestodes.     

Balb/Cj male mice do not feminize after infection with larval Taenia crassiceps

Balb/cJ mice fail to mount an immune response capable of clearing infection with larval Taenia crassiceps. Additionally, male Balb/cJ mice display a lag in larval growth of approximately 3 wk as compared to growth in female mice. It has been reported that male Balb/ cAnN mice generate a protective immune response early in infection, and become permissive to larval growth after they feminize (200-fold increase in serum estradiol and 90% decrease in serum testosterone). To determine if a different strain of Balb/c mice (Balb/cJ) also feminize, serum was collected from infected male mice for 16 wk and levels of 17-beta-estradiol and testosterone were measured via ELISA. In addition, the mounting responses of 12- and 16-wk infected male mice, as well as uninfected control mice, were determined after isolation with a female mouse. The results of these experiments show that male Balb/cJ mice do not feminize during infection with larval T. crassiceps. There was no significant change in serum levels of either 17-beta-estradiol or testosterone during the course of infection (> 16 wk). Moreover, there was no significant decrease in the number of times infected male mice mounted the female mouse as compared to uninfected controls. These results suggest that there may be variances between the substrains of Balb/c mice that lead to the phenotypic differences reported for male Balb/cJ and Balb/cAnN mice.     

The growth of the metacestodes of Taenia crassiceps in white mice.

The effect of the sex of the intermediate host on the growth and development of the metacestodes of Taenia crassiceps has been investigated. Three different strains of mice were used, the C R S, L A C A and C F L P strains and two strains of metacestode, the Toi and the E R S strains. The results show that matacestodes of T. crassiceps grow and multiply more rapidly in female than in male mice, although both sexes are equally susceptible to the infection. The origin of the parasite, i.e., from a rat or mouse host, affects the parasite growth.     

Immunological mediation of gonadal effects on experimental murine cysticercosis caused by Taenia crassiceps metacestodes.

Female BALB/c mice are naturally more susceptible than males to intraperitoneal experimental infection with Taenia crassiceps metacestodes. Gonadectomy tends to equalize susceptibility between sexes by reducing in half the mean individual intensity of females and by tripling that of males. The effect of gonadectomy is seen only in mice with intact immune systems but not in irradiated mice. Purified sex hormones (17-beta estradiol, testosterone, and progesterone) do not affect cysticercus reproduction or growth in vitro. Thus, gonadal effect on mouse susceptibility to cysticercosis appears to be mediated via the immune system, and it is probably not the consequence of the major sex steroids acting directly upon the parasites. Because sublethal irradiation increases the intensity in gonadectomized females and intact males, whereas that of gonadectomized males and intact females remains unchanged, irradiation results are consistent with the hypothesis that immunological events that participate in controlling the growth of cysticerci are inhibited by ovaries and stimulated by testes.     

Fatal cysticercosis by Taenia crassiceps (Cyclophyllidea: Taeniidae) in a presumed immunocompromised canine host

Cysticercosis in a canine host (Canis familiaris) attributable to the taeniid cestode Taenia crassiceps is reported for the first time in North America. Numerous parent and daughter cysticerci occurred in a massive intrapleural and intraperitoneal infection in an apparently immunocompromised host. The largest cysticerci were ovoid to elongate, 5-9 mm in maximum length, and armed with 32-34 rostellar hooks in 2 rows; small hooks measured 114-143 microm long (x = 124+/-8.2 microm), and large hooks were 156-180 microm (x = 163+/-7.4 microm). Taenia crassiceps is widespread in boreal North America and, like a number of other taeniids, constitutes a potential risk as a zoonotic parasite. The immunological status of the host may be important in determining the outcome of infections for this and other taeniids in atypical hosts.     

Changes in hepatic lipids of mice infected with cysticerci of Taenia crassiceps

Nuclear magnetic resonance (NMR) spectroscopy was employed to investigate the effect of infection with Taenia crassiceps cysticerci on the lipid profile of mouse liver. Chloroform/methanol extracts of livers from infected mice showed lower concentrations of phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, total glycerophospholipid, triacylglycerol, total fatty acid (FA) and all measured FA components than those from controls. Furthermore, the ratios obtained on dividing concentrations of the FA components by that of total FA demonstrate that the concentration decreases caused by infection are less for polyunsaturated fatty acids (FAs) than for other FAs. Extracts of T. crassiceps displayed a similar lipid profile to that of host liver but contained a lower lipid content and a shorter average FA chain length.     

Extravascular inflammation does not increase atherosclerosis in apoE-deficient mice

There is much speculation whether extravascular inflammation accelerates atherosclerosis. We tested this hypothesis in apoE^−/− mice using three well-characterized models of non-autoimmune chronic inflammation: croton oil-induced skin inflammation, Aspergillus fumigatus antigen-induced allergic lung disease, and A. fumigatus antigen-induced peritonitis. The croton oil model produced recurrent inflammatory skin ulceration, and marked increases in plasma levels of IL-6 and serum amyloid A (SAA). The allergic lung disease model showed strong local inflammation with eosinophilic infiltration and serum IgE induction. The recurrent peritonitis model was accompanied by mild elevation in plasma SAA levels. Aortic atherosclerosis was quantified by computer-assisted morphometry of en face arteries in apoE^−/− mice at 34 weeks for the croton oil model, 26 and 42 weeks for the allergic lung disease model, and 26 weeks for the peritonitis model. We found that all three forms of chronic extravascular inflammation had no effect on the rate of atherosclerosis development.     

Subcutaneous cysticercosis due to Taenia crassiceps (Cestoda: Taeniidae) in an imported steppe lemming in Japan

This study describes a subcutaneous proliferative cysticercosis in a pet steppe lemming, Lagurus lagurus (Rodentia: Cricetidae), bred and imported from Czech Republic into Japan. Numerous metacestodes were collected from the subcutaneous cystic lesion of the left medial thigh. Four surgical removals were coupled with anthelmintic treatment but ended with recurrence. Based on morphological features and mitochondrial DNA sequences, the metacestodes were identified as the larval stage of Taenia crassiceps (Zeder, 1800). This is the first case of infection with larval T. crassiceps in rodents of the genus Lagurus, and becomes the third case of the parasite detected from imported animals in Japan. Related public health concerns are discussed.     

Taenia crassiceps organic acids detected in cysticerci

Taenia crassiceps cysticerci is used as an experimental model to cysticercosis studies; however there are subcutaneous cases of cysticercosis caused by these cysticerci. It remains unclear in the literature the energetic and fatty acid metabolism in cestodes. Its metabolic study may provide knowledge of pathways that may serve as potential anti-helminthic drugs sites of action. In this work we studied the citric acid cycle organic acids and the fatty acid oxidation in cysticerci removed from mice with 21 and 42 days of infection in two different evolutive stages: growing and final. The organic acids were extracted using perchloric acid and analyzed by HPLC methodology. We found significant statistically differences in oxalate, malate, lactate, and beta-hydroxybutirate concentrations between cysticerci. These results indicate the aerobic metabolism in vivo in spite of the low oxygen concentration of its habitat, and also indicate the presence of fatty acid oxidation as an alternative energetic source.     

Metabolism of steroid hormones by Taenia solium and Taenia crassiceps cysticerci

Previous in vitro experiments showed that both, Taenia crassiceps and Taenia solium cysticerci have the ability to metabolize exogenous androstenedione to testosterone. Here we evaluate on the capacity of both cysticerci to synthesize several sex steroid hormones, using different hormonal precursors. Experiments using thin layer chromatography (TLC) showed that both cysticerci were able to produce ³H-hydroxyprogesterone, ³H-androstenedione and ³H-testosterone when ³H-progesterone was used as the precursor. They also synthesized ³H-androstenediol and ³H-testosterone when ³H-dehydroepiandrosterone was the precursor. In addition, both cysticerci interconverted ³H-estradiol and ³H-estrone. These results, strongly suggest the presence and activity of the Δ4 and Δ5 steroid pathway enzymes, 3β-hydroxysteroid dehydrogenase/Δ^5-4 isomerase-like enzyme (3β-HSD), that converts androstenediol into testosterone; and the 17β-hydroxysteroid dehydrogenase that interconverts estradiol and estrone, in both types of cysticerci.