Rat Tapeworm Hymenolepis Diminuta Research Articles

A66 EFFECTS OF HYMENOLEPIS DIMINUTA EXTRACELLULAR VESICLES ON MOUSE MACROPHAGES AND THEIR MITOCHONDRIA

Abstract Background In recent years, extracellular vesicles (EVs) have emerged as important means of intercellular communication and immune modulation between helminth and host. Earlier work revealed that excretory/secretory products from the rat tapeworm Hymenolepis diminuta (HES) have anti-inflammatory properties when applied to macrophages. In this study, we have investigated the immunomodulatory properties of H. diminuta EVs (HEVs) on macrophages. Aims 1. To isolate and characterize bacterial contaminant-free H. diminuta EVs (Hd-EVs). 2. To determine the effects of Hd-EVs on murine macrophage metabolism and LPS-evoked cytokine production. Methods Adult H. diminuta were cultured for 6h in serum-free RMPI and Hd-EVs isolated from the conditioned medium using an exoEasy kit. Hd-EV protein content was measured using a micro-BCA kit, and size and quantity were measured using Nanosight tracking analysis. Murine bone marrow-derived macrophages or the human macrophage THP-1 cell line were treated with LPS (10 ng/ml) ± a crude H. diminuta extract (HdE), HES, or Hd-EVs for 24h. TNF-α levels in the culture medium was measured by ELISA. Macrophage oxidative phosphorylation (OX.PHOS) and glycolysis were measured in real-time using an Agilent Seahorse XF Analyzer. Results Analysis of 14 Hd-EV samples revealed 4.1 X 109 - 5.48 X 1010 particles/mL, with Hd-EVs predominantly 100-350 nm in diameter and with a protein content of 64.9-181.6 ng/mL. HdE and HES reduced TNF-α production in LPS-activated macrophages by 39-76% (n=11), while Hd-EVs did not lower TNF-α production. Metabolic analysis suggests that HES and Hd-EVs can up-regulate macrophage glycolysis, while only Hd-EVs exposed macrophages showed increased OX.PHOS (n=6). Conclusions We have successfully isolated and begun to characterize EVs from adult H. diminuta. Despite the known abilities of HES, we unexpectedly noted that exposure to Hd-EVs did not result in a statistically significant decrease in macrophage TNF-α release. However, the increase in OX.PHOS macrophages treated with Hd-EVs is something to examine further. The next steps are to determine the contents and immunomodulatory activity of the Hd-EVs, thus advancing knowledge of how helminths can manipulate their hosts. Funding Agencies NSERC Clinical Practice

Human infections by the rat tapeworm Hymenolepis diminuta in China.

The rat tapeworm Hymenolepis diminuta is a parasite that usually uses rats as a definitive host. It also infects humans and non-human primates. Human infections have been reported in 80 countries worldwide, including China. Nevertheless, nearly all the literature on human infections in China by the rat tapeworm is in Chinese journals, which are very difficult to access by readers outside China. The main aim of the current manuscript was to systematically review human infections by the rat tapeworm in China for readers inside and outside the country. Chinese characters for H. diminuta were used to search several databases, including Google Scholar. In total, 511 infections were reported in 24 Chinese provinces/autonomous regions, which surpassed 320 in Costa Rica as the country with the highest number of infections. Furthermore, three nationwide surveys on parasitic infections in the past 3 decades revealed detailed prevalence of this parasite along with that of roundworm, whipworm, hookworm and pinworm in Chinese populations. These data contribute to better understanding of this greatly neglected zoonosis in the world's most populated country.

Gallic acid and Catechin induce morphological alterations on the zoonotic parasite Hymenolepis diminuta.

Tapeworm infections cause insidious and irreversible effects in the infected individuals and some of them have already shown resistance to available drugs. A search for alternative treatment is urgently required. Phenolic compounds are amongst the most researched natural substances for their medicinal use. The present study aims to determine anthelmintic efficacy of two polyphenols Gallic acid and Catechin against the zoonotic rat tapeworm Hymenolepis diminuta. Both compounds are potent anti-oxidants and play major roles in combating pathogens, while their anthelmintic property according to our knowledge is yet to be explored. The parasite model H. diminuta was procured from intestine of infected rats raised in our laboratory. Two sets of parasites were treated in vitro with 5, 10, 20 and 40mg/ml concentrations of each Gallic Acid and Catechin separately, another set of parasites were treated with standard dose of Praziquantel in RPMI 1640, while still another set of worms were kept in RPMI 1640 at 37 ± 10C with 1% Dimethyl sulfoxide as control. Motility and structural alterations were the parameters assessed for anthelmintic efficacy of the compounds. After paralysis the worms were processed for morphological, histological, and ultrastructural study and observed under light and electron microscope. Dose-dependent efficacy was observed in both compounds. Shrinkage of suckers, deformed proglottids and architectural alteration of the tegument were observed throughout the body of treated parasites compared to control. Although in terms of time taken for paralysis and mortality Gallic acid was more effective than Catechin, the degree of morphological aberrations caused were almost similar, except histological alteration was more in Catechin treated worms than in Gallic acid. Nevertheless, both Gallic acid and Catechin are suggested to possess anthelmintic efficacy besides other health benefits but extended studies are required to compare their efficacy.

A163 INFECTION WITH HYMENOLEPIS DIMINUTA ELICITS A TH2 IMMUNITY AND ALLEVIATES DNBS-COLITIS IN A MOUSE MODEL WITH MINIMAL INTESTINAL MICROBIOTA

Abstract Background Immunocompetent mice infected with the rat tapeworm Hymenolepis diminuta are protected from dinitrobenzene sulphonic-acid (DNBS)-induced colitis that was accompanied by the increased relative abundance of short-chain fatty acid (SCFA)-producing bacteria and fecal SCFA levels at 8 days post-infection (dpi). These changes were not observed in antibiotic-treated BALB/c mice or germ-free mice. To further characterize the host-parasite-microbiota interaction in the control of colitis, experiments have been conducted in a reductionist system in which the H. diminuta anti-colitic response was tested in mice colonized with 12 commensal bacteria representing the major five phyla of the mouse gut. Purpose To identify key bacterial species and microbe-derived mediators involved in the H. diminuta-induced protection from DNBS-induced colitis. Method OligoMM12 (Oligo-Mouse-Microbiota) mice (n=4-8/group) were infected with 10 viable antibiotic-treated H. diminuta cysticercoids eight days prior to challenge with DNBS (3mg, i.r.). Mice were monitored daily and necropsied 72h post-DNBS. Disease was assessed by a macroscopic disease activity score, colon length and histopathology on H&E sections of mid-colon. Production of IL-4, -5, -10 and -13 by concanavalin-A treated spleen cells by ELISA was used as an index of successful helminth infection. Result(s) OligoMM12 mice treated with DNBS developed acute colitis, with 3/8 mice requiring humane euthanization, while all mice infected with H. diminuta survived the DNBS challenge. Successful infection was confirmed by statistically significant increases in splenic output of the Th2-cytokines in response to mitogenic stimulation and efficient expulsion of the worms burden by 11 dpi. The severity of DNBS-induced colitis was reduced in H. diminuta-infected mice (n=4), although additional experiments are required to confirm the statistical significance of these data. Conclusion(s) Reproducible DNBS-induced colitis in mice with the simplified OligoMM12 consortium of bacteria and reduced disease in H. diminuta-infected mice has created a model by which the participation of exact bacterial groups or species in H. diminuta-induced suppression of colitis can be tested. This is of translational value, since the failure of helminth therapy in IBD could be predicated by dysbiosis in the patient, and therefore potentially overcome by combination therapy of ‘probiotic’ and helminth. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; NSERC-CGS D, Eyes High doctoral Recruitment Scholarship Disclosure of Interest None Declared

Hymenolepis diminuta Infection Affects Apoptosis in the Small and Large Intestine.

The rat tapeworm Hymenolepis diminuta has been shown to cause alterations in gastrointestinal tissues. Since hymenolepiasis induces a number of reactions in the host, it is reasonable to assume that it may also be involved in the mechanisms of apoptosis in the intestines. Individual research tasks included an examination of the effect of H. diminuta infection on; (i) the cellular localization of the expression of pro-apoptotic protein Bax and anti-apoptotic protein Bcl-2, as well as caspase-3 and caspase-9, and (ii) the effects of the infection on the expression of Bcl-2, Bax, Cas-3 and Cas-9, at the mRNA and protein levels. Molecular tests (including mRNA (qRT PCR) and the protein (Western blot) expression of Bax, Bcl-2, and caspases-3, -9) and immunohistochemical tests were performed during the experiment. They showed that H. diminuta infection activates the intrinsic apoptosis pathway in the small and large intestine of the host. H. diminuta infection triggered the apoptosis via the activation of the caspase cascade, including Cas-3 and Cas-9. Hymenolepiasis enhanced apoptosis in the small and large intestine of the host by increasing the expression of the pro-apoptotic gene and protein Bax and by decreasing the expression of the anti-apoptotic gene and protein Bcl-2.

A181 INFECTION WITH THE RAT TAPEWORM HYMENOLEPIS DIMINUTA REVEALS AN INTERLEUKIN-4 INDEPENDENT TUFT CELL ASSOCIATED WITH PEYER’S PATCHES

BackgroundInfection with the rat tapeworm Hymenolepis diminuta elicits a T helper 2 (Th2) imunity and suppresses dinitrobenzene sulphonic-acid-induced colitis in mice. However, the signaling cascade in an immunocompetent host that recognizes and mobilizies early immune events to expel the worm is poorly understood. To fully understand how helminth-infection can ameliorate concomitant disease, it is important to elucidate key cells/mediators in the detection of the worm and early events in the local anti-worm response. Here, we assess the chemosensory epithelial tuft cell and Peyer’s patches (PP) as the primary inductive sites of mucosal immunity in H. diminuta-infected mice.AimsTo assess the role of tuft cells in PP development and worm expulsion following infection of H. diminuta.MethodsBALB/c, BALB/c Il-4receptor-a-/-, C57Bl/6 and C57Bl/6 pou2f3-/- (transcription factor critial for tuft cell development) mice were infected with 5 cysticercoids of H. diminuta and necropsied 5-, 8- and 11-days post-infection (dpi); time-matched non-infected mice served as controls. PP number and size were counted and measured. Enteric tuft cells were assessed by immunostaining for the canonical marker double cortin like kinase (dclk)-1, and enumerated in PP-associated epithelium and villous epithelium distant from PP.ResultsDclkl+ tuft cells were sparse throughout villus epithelium of control mice, but were notably aggregrated over PPs. Infection with H. diminuta resulted in more detectable PPs by visual inspection, but did not result in a statistically significant increase in either size or number of PP. Infected mice showed increased numbers of dclk1+ tuft cells in villus epithelium and PP-associated epithelium (n=3–6). Tuft cells were absent in pou2f3-/- mice, that showed normal size and number of PPs ± infection with H. diminuta. Unexpectedly, analysis of small intestine from il4ra-/- mice revealed dclk1+ tuft cells in association with PPs; perhaps a unique sub-type of this sentinel cell.ConclusionsAnalysis of tuft cells after infection with H. diminuta revealed that these cells aggregate around PPs under homeostatic conditions, and future studies will explore if this distrirbution is important for ‘M’ cell development and/or PP immune reactivity. Intrigingly, an il-4ra-independent tuft cell subtype was observed that awaits fuller characterization. Understanding the tuft cell may reveal novel aspects of development of mucosal immunity relevant to combating helminth-infection and perhaps autoinflammatory enteric disease.Funding AgenciesNSERC

The good, the bad, and the ugly: From planarians to parasites.

Platyhelminthes can perhaps rightly be described as a phylum of the good, the bad, and the ugly: remarkable free-living worms that colonize land, river, and sea, which are often rife with color and can display extraordinary regenerative ability; parasitic worms like schistosomes that cause devastating disease and suffering; and monstrous tapeworms that are the stuff of nightmares. In this chapter, we will explore how our research expanded beyond free-living planarians to their gruesome parasitic cousins. We start with Schistosoma mansoni, which is not a new model; however, approaching these parasites from a developmental perspective required a reinvention that may hold generalizable lessons to basic biologists interested in pivoting to disease models. We then turn to our (re)establishment of the rat tapeworm Hymenolepis diminuta, a once-favorite model that had been largely forgotten by the molecular biology revolution. Here we tell our stories in three, first-person narratives in order to convey personal views of our experiences. Welcome to the dark side.

Effects of tapeworm infection on absorption and excretion of zinc and cadmium by experimental rats.

The main objective of this study was to determine how rat tapeworms affect the excretion of zinc and cadmium through rat feces. Male rats (Rattus norvegicus var. alba) were divided into four groups, and the experiment was conducted over a 6-week period. The control groups (00; 0T) were provided with a standard ST-1 rodent mixture and received 10.5mg of Zn/week. Groups P0 and PT were fed a mixture supplemented with the hyperaccumulating plant Arabidopsis halleri at a dosage of 123mg Zn/week and 2.46mg Cd/week. Groups 0T and PT were infected with the rat tapeworm (Hymenolepis diminuta). Fecal samples were collected 24h post exposure. Zinc and cadmium concentrations in rat feces were analyzed using inductively coupled plasma optical emission spectrometry. Tapeworm presence decreased the amount of metals excreted through the feces of the host throughout the entire experiment, with the exception of 1week (control group). No statistically significant differences between zinc excretion rates in the control groups (00 and 0T) were detected at any time throughout the experiment. A statistically significant difference between zinc excretion rates (p < 0.05) in the exposed groups (P0 and PT) was detected in 2 of the 6 monitored weeks. Group PT excreted significantly less cadmium (p < 0.01) than group P0 did in three of the 6weeks. Overall, our results indicate that tapeworms are able to influence the excretion of metals by their host. Tapeworms accumulate metals from intestinal contents. It is not clear whether tapeworms carry out this process before the host tissues absorb the metals from the intestines or the tapeworms accumulate metals excreted from the body of the host back to the intestines. Most likely, it is a combination of both phenomena.

Selected Molecular Mechanisms Involved in the Parasite⁻Host System Hymenolepis diminuta⁻Rattus norvegicus.

The rat tapeworm Hymenolepis diminuta is a parasite of the small intestine of rodents (mainly mice and rats), and accidentally humans. It is classified as a non-invasive tapeworm due to the lack of hooks on the tapeworm’s scolex, which could cause mechanical damage to host tissues. However, many studies have shown that metabolites secreted by H. diminuta interfere with the functioning of the host’s gastrointestinal tract, causing an increase in salivary secretion, suppression of gastric acid secretion, and an increase in the trypsin activity in the duodenum chyme. Our work presents the biochemical and molecular mechanisms of a parasite-host interaction, including the influence on ion transport and host intestinal microflora, morphology and biochemical parameters of blood, secretion of antioxidant enzymes, expression of Toll-like receptors, mechanisms of immune response, as well as the expression and activity of cyclooxygenases. We emphasize the interrelations between the parasite and the host at the cellular level resulting from the direct impact of the parasite as well as host defense reactions that lead to changes in the host’s tissues and organs.

The identification of risk and essential elements along the strobila of the rat tapeworm Hymenolepis diminuta.

The rat tapeworm Hymenolepis diminuta can bioconcentrate several elements to conspicuously higher concentrations than tissues of their definitive host. The main aim of this study was to locate parts of the tapeworm into which lead, cadmium, zinc, copper, manganese and iron are accumulated. Male Wistar rats were experimentally infected with H. diminuta and worms were exposed to two different forms of lead for 6 weeks through the oral exposure of their rat hosts. After the exposure period, the element levels were determined in the posterior and anterior proglottids of the tapeworm. In all cases, lead concentrations were higher in the anterior parts than the posterior parts. Concentrations of cadmium, copper, iron, manganese and zinc were also significantly higher in the anterior parts. Zinc concentrations showed an opposite trend, with higher zinc levels detected in the posterior part of the strobila, in the control group. The present study demonstrates that risk and essential elements are accumulated mainly into the anterior part of H. diminuta.

How the tapeworm Hymenolepis diminuta affects zinc and cadmium accumulation in a host fed a hyperaccumulating plant (Arabidopsis halleri).

The effects of plant-bound zinc (Zn) and cadmium (Cd) on element uptake and their interactions in a parasite-host system were investigated in a model experiment. Male Wistar rats were divided into four groups (C, P, TC and TP). Groups TC and TP were infected with the rat tapeworm Hymenolepis diminuta. Groups C and TC were fed a standard rodent mixture (ST-1) and received 10.5mg of Zn per week, while groups P and TP were fed a mixture supplemented with the Zn- and Cd-hyperaccumulating plant Arabidopsis halleri at a dosage of 236mg Zn/week and 3.0mg Cd/week. Rats were euthanized after 6weeks, and Cd and Zn levels were determined in rat and tapeworm tissue. The results indicate that tapeworm presence did have an effect on Cd and Zn concentrations in the host tissue; the majority of tissues in infected rats had statistically significant lower Zn and Cd concentrations than did uninfected rats. Tapeworms accumulated more zinc and cadmium than did the majority of host tissues. This important finding confirms the ability of tapeworms to accumulate certain elements (heavy metals) from the host body to their own body tissues. Thus, tapeworms can decrease heavy metal concentrations in host tissues.

Rehydration methods to recover cysticercoids of the rat tapeworm Hymenolepis diminuta from dry flour beetle carcasses.

Terrestrial arthropods host a variety of helminth parasites, yet quantifying the intensity of infection in these hosts post-mortem is challenging because carcasses may desiccate quickly. We recovered cysticercoids of Hymenolepis diminuta from desiccated flour beetle (Tribolium confusum) carcasses by modifying a published insect rehydration procedure. Without rehydration, carcasses dissected more than 1 day post-mortem had noticeable degradation of cysticercoids. Mild rehydration (soaking in water only for 2 days, or 0.5-10% KOH for 1 h followed by 1 day in water, or 0.5% KOH for 1 day) left carcasses tough and time-consuming to dissect, but all parasites could be recovered and were similar in body size to fresh cysticercoids. Moderate rehydration (5-10% KOH for 1 day) allowed all parasites to be recovered and facilitated dissection by partially dissolving internal organs of the beetle while causing little degradation of the cysticercoids. Harsh rehydration (5-10% KOH for 1 day followed by 5 days in water) not only dissolved internal beetle tissues but also severely damaged cysticercoids, such that parasite counts were unreliable. The degree of initial carcass desiccation had little effect on results following rehydration. However, regardless of treatment used, intact cercomers were rarely retained on rehydrated cysticercoids. Rehydration was less successful on early developmental stages of the parasite, which were recovered reliably only as they neared the cysticercoid stage. This method has utility for studies of parasite-induced mortality by permitting accurate and reliable parasite counts from dead, desiccated hosts.

Fine-Scale Analysis of Parasite Resistance Genes in the Red Flour Beetle, Tribolium castaneum

Parasite infection impacts population dynamics through effects on fitness and fecundity of the individual host. In addition to the known roles of environmental factors, host susceptibility to parasites has a genetic basis that has not been well characterized. We previously mapped quantitative trait loci (QTL) for susceptibility to rat tapeworm (Hymenolepis diminuta) infection in Tribolium castaneum using dominant AFLP markers; however, the resistance genes were not identified. Here, we refined the QTL locations and increased the marker density in the QTL regions using new microsatellite markers, sequence-tagged site markers, and single-strand conformational polymorphism markers. Resistance QTL in three linkage groups (LG3, LG6, and LG8) were each mapped to intervals <1.0 cM between two codominant markers. The effects of 21 genes in the three QTL regions were investigated by using quantitative RT-PCR analysis, and transcription profiles were obtained from the resistant TIW1 and the susceptible cSM strains. Based on transcription data, eight genes were selected for RNA interference analysis to investigate their possible roles in H. diminuta resistance, including cytochrome P450 (LOC657454) and Toll-like receptor 13 (TLR13, LOC662131). The transcription of P450 and TLR13 genes in the resistant TIW1 strains was reduced more than ninefold relative to the control. Moreover, the effects of gene knockdown of P450 and TLR13 caused resistant beetles to become susceptible to tapeworm infection, which strongly suggests an important role for each in T. castaneum resistance to H. diminuta infection.

The activity of drug-metabolizing enzymes and the biotransformation of selected anthelmintics in the model tapeworm Hymenolepis diminuta

The drug-metabolizing enzymes of some helminths can deactivate anthelmintics and therefore partially protect helminths against these drugs' toxic effect. The aim of our study was to assess the activity of the main drug-metabolizing enzymes and evaluate the metabolism of selected anthelmintics (albendazole, flubendazole, mebendazole) in the rat tapeworm Hymenolepis diminuta, a species often used as a model tapeworm. In vitro and ex vivo experiments were performed. Metabolites of the anthelmintics were detected and identified by HPLC with spectrofluorometric or mass-spectrometric detection. The enzymes of H. diminuta are able to reduce the carbonyl group of flubendazole, mebendazole and several other xenobiotics. Although the activity of a number of oxidation enzymes was determined, no oxidative metabolites of albendazole were detected. Regarding conjugation enzymes, a high activity of glutathione S-transferase was observed. A methyl derivative of reduced flubendazole was the only conjugation metabolite identified in ex vivo incubations of H. diminuta with anthelmintics. The results revealed that H. diminuta metabolized flubendazole and mebendazole, but not albendazole. The biotransformation pathways found in H. diminuta differ from those described in Moniezia expanza and suggest the interspecies differences in drug metabolism not only among classes of helminths, but even among tapeworms.

The inability of tapeworm Hymenolepis diminuta and fluke Dicrocoelium dendriticum to metabolize praziquantel

Biotransformation enzymes can, to a certain extent, protect parasitic worms against the toxic effects of anthelmintics and can contribute to drug-resistance development. The objective of our work was (1) to find and identify phase I and II metabolites of the anthelmintic praziquantel (PZQ) formed by the lancet fluke (Dicrocoelium dendriticum) and the rat tapeworm (Hymenolepis diminuta) and (2) to compare PZQ metabolites in helminths with PZQ biotransformation in rat as host species. Ultra high performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS) was used for this purpose. During in vitro incubations, mitochondria-like and microsomes-like fractions (prepared from homogenates of adult worms or from rat liver homogenate) were incubated with 10 and 100μM PZQ. Liquid/liquid extraction was used for samples during in vitro experiments. In the ex vivo study, living D. dendriticum and H. diminuta adults were incubated in RPMI-1640 medium in the presence of 50nM or 100nM PZQ for 24h. After incubation, the worms were removed from the medium and homogenized. Homogenates of worms, medium from the incubation of worms or rat hepatocytes and rat urine (collected during 24h after oral PZQ administration) were separately extracted using solid-phase extraction.The results showed that both D. dendriticum and H. diminuta enzymatic systems are not able to metabolize PZQ. On the other hand, thirty one different phase I and four phase II PZQ metabolites were detected in rat samples using UHPLC/MS/MS analyses. These results show that our experimental helminths, as the members of tapeworm and fluke groups of parasites, are not able to deactivate PZQ, and that the biotransformation enzymes of the studied helminths do not contribute to PZQ-resistance.

Effects of high pressure processing on hatching of eggs of the zoonotic rat tapeworm Hymenolepis diminuta

High hydrostatic pressure processing (HPP) is an effective non-thermal treatment to remove pathogens from a variety of food and food products. It has been extensively examined using prokaryotic organisms but has had limited study on eukaryotic organisms. Treatment using HPP has been shown to be effective in inactivating nematode larvae in food and Ascaris suum eggs. Nothing is known on the efficacy of HPP on tapeworm cysts or eggs. Eggs of important zoonotic tapeworms including Echinococcus and Taenia spp. can potentially contaminate water and food intended for human consumption. The present study examined the efficacy of HPP on the viability of Hymenolepis diminuta eggs. Efficacy of HPP treatment was measured using an egg hatch assay in two experiments. One thousand unhatched H. diminuta eggs in Hanks balanced salt solution were packaged in sealable bags and exposed to 100–600megapascals (MPa; 1MPa=10atm=147psi) for 60s in a commercial HPP unit. Positive (no HPP) and negative (No HPP but frozen/thawed) controls were examined in each experiment. None of the HPP untreated and frozen eggs (negative controls) were able to hatch or exclude trypan blue when placed in the hatching solution in experiment 1 or 2. HPP untreated and nonfrozen eggs (positive controls) hatched and excluded trypan blue; 75% were positive in experiment 1 and 80% were positive in experiment 2. No hatched eggs were observed when they were exposed to 300–600MPa for 60s. Treatment at 400MPa and above caused rupturing of the oncosphere. Results from this study indicate that HPP is a possible method to inactivate tapeworm eggs and that the susceptibility of tapeworm eggs to HPP is similar to or greater than that of nematode eggs or tissue larvae.

Tapeworm (Hymenolepis diminuta) infection in flour beetles (Tribolium confusum): does it cause a trade-off between host fecundity and egg size?

Inter- and intra-specific comparisons commonly reveal an inverse relationship between fecundity and offspring size. Many animals also vary egg size in response to environmental conditions. Infection of flour beetles Tribolium confusum Jaquelin Du Val, 1868 with the rat tapeworm Hymenolepis diminuta (Rudolphi, 1819) causes a major reduction in host fecundity. This study tested if this fecundity reduction was associated with changes in host egg size. Age-matched beetles were either fasted and then exposed to parasites, fasted only, or neither, and egg production and egg length determined for 5 weeks postexposure. Control beetles that were neither fasted nor exposed to parasites had steady egg production, but produced smaller eggs as they aged. Beetles that were fasted only, produced fewer but larger eggs for 1–2 weeks after the fast ended. Then, fecundity and egg size returned to control levels. Infected beetles also produced fewer, larger eggs for 1–2 weeks, but at levels indistinguishable from beetles that had been fasted only. After 2 weeks, while fecundity of infected beetles remained low, egg size became similar to noninfected hosts. Beetles appeared to trade-off fecundity and egg size in response to reduced feeding, but not to the presumed nutritional stress of parasitic infection.

Inflammatory Bowel Disease and Trichuris muris

Inflammatory bowel disease (IBD) is a group of idiopathic chronic relapsing inflammatory conditions of the gastrointestinal tract. The precise etiology of IBD is unknown, although it is clearly multifactorial resulting from interplay of genetic, environmental and immunological factors. Epidemiological studies show that the incidence of IBD and other autoimmune disorders is low in the developing countries and more in the developed countries. Evidence suggests that therapeutic administration of helminth can reduce the symptoms of IBD in both animal models and man. However, one study show the rat tapeworm Hymenolepis diminuta infection results in significant exacerbation of oxazolone induced colitis in mice (Hunter et al., 2007). The mechanisms by which helminths interact with the gut immune system in IBD-susceptible hosts, particularly their effect on the onset and progression of colitis are poorly understood. To address this we have investigated the interaction between Trichuris muris and the mdr1a (-/-) mouse model, which lacks the epithelial barrier protein, p-glycoprotein and slowly develops a spontaneous colitis in the presence of a normal gut flora.

Helminth Infection Enhances Disease in a Murine TH2 Model of Colitis

There is convincing evidence from animal and human studies that infection with parasitic helminths can alleviate the histopathology and symptoms of colitis. Here the ability of the rat tapeworm Hymenolepis diminuta to affect the course of oxazolone-induced colitis (a TH2 model) was assessed. Mice were infected with H diminuta and 8 days later they received oxazolone (3 mg in 50% EtOH, intrarectal). On autopsy (3 or 7 days postoxazolone), disease severity was assessed by macroscopic clinical scores, histologic damage scores, myeloperoxidase and eosinophil peroxidase activity, and cytokine synthesis. As gauged by all markers of gut function, infection with H diminuta caused a significant exacerbation of oxazolone-induced colitis. Indeed, while mice receiving oxazolone only began to recover approximately 3-4 days posttreatment, the cotreated group continued to deteriorate. Helminth infection, independent of oxazolone administration, enhanced IL-4, IL-5, IL-10, and IL-13 production from in vitro stimulated immune cells and evoked increases in colonic eosinophil peroxidase of cotreated mice. Finally, while knockout of natural killer (NK) and NK-T cells by administration of a neutralizing NK1.1 antibody reduced the inflammation in oxazolone and oxazolone + H diminuta-treated animals, mice in the latter group still displayed significant colitis. We have shown that H diminuta infection is beneficial in other models of colitis. The current data is presented as a caveat to the position that parasitic helminths in general can be considered as a therapy for heterogeneous inflammatory disorders without careful analysis of the immunologic basis of the condition.

A behavioral study of the beetle Tenebrio molitor infected with cysticercoids of the rat tapeworm Hymenolepis diminuta

The host-parasite relationship, Tenebrio molitor-Hymenolepis diminuta, was analyzed. The learning behavior of infected and uninfected (control) beetles in a T-maze was compared. The infected beetles moved much slower in the T-maze than the controls. The infected beetles reached the same level of learning as the controls. However, they needed more trials than the controls. The effect of the infection was already distinct after the first week and even higher after the second week. This indicates that the initial phase of infection caused stress in the beetles. Longer infection did not worsen their ability to learn. Thus, the parasites clearly changed the behavior of their intermediate host and probably made them more susceptible to their final host, the rat.