TLR2 mediates immunity to experimental cysticercosis

Information concerning TLR-mediated antigen recognition and regulation of immune responses during helminth infections is scarce. TLR2 is a key molecule required for innate immunity and is involved in the recognition of a wide range of viruses, bacteria, fungi and parasites. Here, we evaluated the role of TLR2 in a Taenia crassiceps cysticercosis model. We compared the course of T. crassiceps infection in C57BL/6 TLR2 knockout mice (TLR2^-/-) with that in wild type C57BL/6 (TLR2^+/+) mice. In addition, we assessed serum antibody and cytokine profiles, splenic cellular responses and cytokine profiles and the recruitment of alternatively activated macrophages (AAMφs) to the site of the infection. Unlike wild type mice, TLR2^-/- mice failed to produce significant levels of inflammatory cytokines in either the serum or the spleen during the first two weeks of Taenia infection. TLR2^-/- mice developed a Th2-dominant immune response, whereas TLR2^+/+ mice developed a Th1-dominant immune response after Taenia infection. The insufficient production of inflammatory cytokines at early time points and the lack of Th1-dominant adaptive immunity in TLR2^-/- mice were associated with significantly elevated parasite burdens; in contrast, TLR2^+/+ mice were resistant to infection. Furthermore, increased recruitment of AAMφs expressing PD-L1, PD-L2, OX40L and mannose receptor was observed in TLR2^-/- mice. Collectively, these findings indicate that TLR2-dependent signaling pathways are involved in the recognition of T. crassiceps and in the subsequent activation of the innate immune system and production of inflammatory cytokines, which appear to be essential to limit infection during experimental cysticercosis.     

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.     

Epidemiological understanding of Taenia tapeworm infections with special reference to Taenia asiatica in Korea.

In endemic areas of Taenia tapeworms in Korea, most of the reports showed that T. saginata was dominant over T. solium, but eating pigs is the dominant habit over eating cattle. Why do they have more T. saginata despite lower consumption of beef? This problem actually has long been recognized but until recently there has been no intensive trial to give a scientific explanation on this epidemiological enigma. By summing up the data published between the years 1963 and 1999, the ratio of armed versus unarmed tapeworms in humans was estimated at approximately 1:5. The ratio of pig-eaters versus cattle-eaters, however, was approximately 5:1. This inconsistency could be explained with the recently described T. asiatica, which infects humans through the eating of pig''s viscera. We re-evaluate the importance of the consumption of visceral organ of pigs, leading us to an improved epidemiological understanding of the T. asiatica infection together with co-existing T. saginata and T. solium in Korea.     

Intestinal helminths infection of rats (Ratus norvegicus) in the Belgrade area (Serbia): the effect of sex, age and habitat

SUMMARY: Gastrointestinal helminths of Norway rat (Rattus norvegicus) from the Belgrade area were studied as a part of a wider ecological research of rats in Serbia (data on the distribution, population ecology, economic and epizoothiological-epidemiological importance, and density control). Rats were captured from May 2005 to July 2009 at both urban and suburban-rural sites. Of a total of 302 trapped rats 48% were males and 52% females, with 36.5% and 38.8% of juvenile-subadult individuals, per sex respectively. Intestinal helminth infection was noted in 68.5% of rats, with a higher prevalence in male hosts and in adult individuals. Higher numbers of infected juveniles-subadults were noted in suburban-rural habitats, while an opposite tendency was noted in adult rats. Seven helminth species were recovered, of which five were nematode (Heterakis spumosa, Nippostrongylus brasiliensis, Capillaria sp., Trichuris muns and Syphacia muris) and two cestode species (Hymenolepis diminuta and Rodentolepis fraterna). The most prevalent parasites were Heterakis spumosa (36.7%) and Hymenolepis diminuta (30.5 %). Sex and habitat-related differences were noted in the prevalence of infection with Capillaria sp. and Trichuris muris, while there were no age-related differences in the prevalence of infection with any individual helminth species. Significantly higher prevalence of infection was noted in summer as compared to spring or winter, with a tendency to be higher in autumn as compared to spring. The only significant difference in the prevalence of infection between habitat-related was noted during spring. H. spumosa was most prevalent in summer, while H. diminuta and N. brasiliensis in autumn. The mean intensity of infection with H. spumosa, R. fraterna, S. muris and T muris was higher in autumn than in the other seasons, while N. brasiliensis and Capillaria sp. occured in winter. No more than four helminth species were found in one host.     

Impaired pro-inflammatory cytokine production and increased Th2-biasing ability of dendritic cells exposed to Taenia excreted/secreted antigens: A critical role for carbohydrates but not for STAT6 signaling

In cysticercosis, a parasitic disease caused by cestodes, the details of early interactions between parasite antigens and innate cells from the host are not well understood. In this study, the role of cestode-conditioned dendritic cells (DCs) in priming Th1 versus Th2 responses to bystander antigen was examined by using CD11c⁺ DCs as antigen-presenting cells and naive CD4⁺ DO11.10 lymphocytes specific to ovalbumin (OVA) as responding cells. No conventional maturation was induced in DCs exposed to Taenia crassiceps excreted/secreted antigens (TcES). The ability of TcES to affect Toll-like receptor (TLR)-mediated maturation and the pro-inflammatory response was analyzed by co-pulsing DCs with TcES and TLR ligands. DCs exposed to TcES blocked TLR4, TLR9 and Toxoplasma soluble antigen-induced phenotypic maturation. TcES-exposed DCs also blocked secretion of pro-inflammatory cytokines and alloreactive T cell proliferation, while preserving IL-10 production. DCs pulsed with TcES + OVA suppressed IFN-γ, whereas they induced greater IL-4 production by CD4⁺ DO11.10 cells. TcES with chemically-altered glycans failed to modulate TLR-mediated activation of DCs and their Th1-inhibitng ability, which was STAT6-independent. Our results reflect the capacity of TcES glyco-antigens to modulate Th1-type and inflammatory responses mediated through DC activation.     

Current Status and Perspectives of Cysticercosis and Taeniasis in Japan

This mini-review describes recent epidemiological trends in cysticercosis and taeniasis in Japan. Some of the topics discussed herein were presented at the first symposium on "Current perspectives of Taenia asiatica researches", that was held in Osong in Chungbuk Province, South Korea, in October 2011 and organized by Prof. K. S. Eom, Chungbuk National University School of Medicine. To better understand the trends in the occurrence of cysticercosis and taeniasis in Japan, clinical cases reported in 2005 have been updated. In addition, the current status of Taenia asiatica infections successively occurring in Japan since 2010 is also discussed.     

The earliest Mesopsychidae and revision of the family Mesopanorpodidae (Mecoptera)

The family Mesopanorpodidae is revised. Most taxa referred to this family are not related to the type genus Mesopanorpodes Tillyard, 1918. The type species of the latter, Mesopanorpodes wianamattensis,is closely related to Mesopsyche Tillyard, 1917. Therefore Mesopanorpodes is transferred to Mesopsychidae Tillyard, 1917 (= Mesopanorpodidae Tillyard, 1918, syn. n.).The earliest Mesopsychidae are described from the Upper Permian of European Russia (Severodvinian; Isady locality, Vologda Province): Permopsyche issadensisgen. etsp. n. (type species) and Permopsyche rasnitsynisp. n. Two species described under Mesopanorpodes from the Upper Permian of Australia are also included into Permopsyche: Permopsyche belmontensis (Riek, 1953), comb. n., Permopsyche robustus (Riek, 1953) comb. n. The first pre-Triassic Mesopsyche, Mesopsyche incompletasp. n. is described from the uppermost Permian (the town of Vyazniki, Vladimir Province). Bittacopanorpa javorskii Zalessky, 1935 from the uppermost Permian or basal Triassic of Kuznetsk Basin is identified as a hindwing of Mesopsyche: Mesopsyche javorskii (Zalessky, 1935) comb. n. The origin, evolutionary history, and stratigraphic occurrence of Mesopsychidae are discussed.     

The spider family Selenopidae (Arachnida, Araneae) in Australasia and the Oriental Region

We relimit and revise the family Selenopidae to include four new genera and 27 new species from Australia and the Oriental Region. The family is redefined, as are the genera Anyphops Benoit, Garcorops Corronca, Hovops Benoit, Selenops Latreille, and Siamspinops Dankittipakul & Corronca, to accommodate the new genera and to correct previous inconsistencies in the diagnoses and definitions of the aforementioned genera. The species of Selenops that occur throughout India and China are also reviewed. Three species occur in China: Selenops bursarius Karsch 1879, also known from Japan, Korea and Taiwan, Selenops ollarius Zhu, Sha, & Chen 1990, and Selenops radiatus Latreille 1819, the type of the genus and most widespread selenopid. Selenops cordatus Zhu, Sha & Chen syn. n. is recognized as a junior synonym of Selenops radiatus. Amamanganopsgen. n. is monotypic, with Amamanganops baginawasp. n. (♀; from the Philippines). Godumopsgen. n. is monotypic, with Godumops caritussp. n. (♂; from Papua New Guinea). Karaopsgen. n. occurs throughout Australia and includes 24 species. A new combination is proposed for Karaops australiensis (L. Koch 1875) comb. n. (ex. Selenops), and the new species: Karaops gangariesp. n. (♀, ♂), Karaops monteithisp. n. (♀), Karaops alanlongbottomisp. n. (♂), Karaops keithlongbottomisp. n. (♂), Karaops larryoosp. n. (♂), Karaops jarritsp. n. (♂,♀), Karaops marrayagongsp. n. (♀), Karaops ravenisp. n. (♂,♀), Karaops badgeraddasp. n. (♀), Karaops burbidgeisp. n. (♂,♀), Karaops karrawarlasp. n. (♂,♀), Karaops julianneaesp. n. (♀), Karaops martamartasp. n. (♀), Karaops manaaynsp. n. (♀, ♂), Karaops vadlaadambarasp. n. (♀, ♂), Karaops pilkingtonisp. n. (♀, ♂), Karaops deserticolasp. n. (♀), Karaops ngarutjaranyasp. n. (♂,♀), Karaops francesaesp. n. (♂,♀), Karaops toolbrunupsp. n. (♀, ♂), the type species Karaops ellenaesp. n. (♂,♀), Karaops jenniferaesp. n. (♀), and Karaops dawarasp. n. (♀).The genus Makdiopsgen. n. contains five species from India and Nepal. A new combination is proposed for Makdiops agumbensis (Tikader 1969), comb. n., Makdiops montigenus (Simon 1889), comb. n., Makdiops nilgirensis (Reimoser 1934) comb. n.,(ex. Selenops). Also, there are two new species the type of the genus Makdiops mahishasurasp. n. (♀; from India), and Makdiops shivasp. n. (♀). The genus Pakawopsgen. n. is monotypic. A new combination is proposed for Pakawops formosanus (Kayashima 1943) comb. n. (ex. Selenops), known only from Taiwan. A new combination is proposed for Siamspinops aculeatus (Simon)comb. n. (ex. Selenops). The distribution and diversity of the studied selenopid fauna is discussed. Finally, keys are provided to all of the selenopid genera and to the species of Karaopsgen. n.and Makdiopsgen. n.     

Oestradiol and progesterone differentially alter cytoskeletal protein expression and flame cell morphology in Taenia crassiceps

We examined the effects of oestradiol (E₂) and progesterone (P₄) on cytoskeletal protein expression in the helminth Taenia crassiceps — specifically actin, tubulin and myosin. These proteins assemble into flame cells, which constitute the parasite excretory system. Total protein extracts were obtained from E₂- and P₄-treated T. crassiceps cysticerci and untreated controls, and analysed by one- and two-dimensional protein electrophoresis, flow cytometry, immunofluorescence and videomicroscopy. Exposure of T. crassiceps cysticerci to E₂ and P₄ induced differential protein expression patterns compared with untreated controls. Changes in actin, tubulin and myosin expression were confirmed by flow cytometry of parasite cells and immunofluorescence. In addition, parasite morphology was altered in response to E₂ and P₄ versus controls. Flame cells were primarily affected at the level of the ciliary tuft, in association with the changes in actin, tubulin and myosin. We conclude that oestradiol and progesterone act directly on T. crassiceps cysticerci, altering actin, tubulin and myosin expression and thus affecting the assembly and function of flame cells. Our results increase our understanding of several aspects of the molecular crosstalk between host and parasite, which might be useful in designing anthelmintic drugs that exclusively impair parasitic proteins which mediate cell signaling and pathogenic reproduction and establishment.     

Extraintestinal Helminth Infection Reduces the Development of Colitis-Associated Tumorigenesis

Colitis-associated colorectal cancer (CAC) is one of the most common cancers and is closely related to chronic or deregulated inflammation. Helminthic infections can modulate inflammatory responses in some diseases, but their immunomodulatory role during cancer development remains completely unknown. We have analyzed the role of Taenia crassiceps-induced anti-inflammatory response in determining the outcome of CAC. We show that extraintestinal T. crassiceps infection in CAC mice inhibited colonic inflammatory responses and tumor formation and prevented goblet cell loss. There was also increased expression of IL-4 and alternatively activated macrophages markers in colonic tissue and negative immunomodulation of pro-inflammatory cytokine expression. In addition, T. crassiceps infection prevented the upregulation of β-catenin and CXCR2 expression observed in the CAC mice, which are both markers associated with CAC-tumorigenesis, and reduced the numbers of circulating and colonic CD11b⁺Ly6C^hiCCR2⁺ monocytes. Thus, immunomodulatory activities induced by helminth infections may have a role in the progression of CAC.     

Amplification, contraction and genomic spread of a satellite DNA family (E180) in Medicago (Fabaceae) and allied genera

Background and Aims

Satellite DNA is a genomic component present in virtually all eukaryotic organisms. The turnover of highly repetitive satellite DNA is an important element in genome organization and evolution in plants. Here we assess the presence and physical distribution of the repetitive DNA E180 family in Medicago and allied genera. Our goals were to gain insight into the karyotype evolution of Medicago using satellite DNA markers, and to evaluate the taxonomic and phylogenetic signal of a satellite DNA family in a genus hypothesized to have a complex evolutionary history.

Methods

Seventy accessions from Medicago, Trigonella, Melilotus and Trifolium were analysed by PCR to assess the presence of the repetitive E180 family, and fluorescence in situ hybridization (FISH) was used for physical mapping in somatic chromosomes.

Key Results

The E180 repeat unit was PCR-amplified in 37 of 40 taxa in Medicago, eight of 12 species of Trigonella, six of seven species of Melilotus and in two of 11 Trifolium species. Examination of the mitotic chromosomes revealed that only 13 Medicago and two Trigonella species showed FISH signals using the E180 probe. Stronger hybridization signals were observed in subtelomeric and interstitial loci than in the pericentromeric loci, suggesting this satellite family has a preferential genomic location. Not all 13 Medicago species that showed FISH localization of the E180 repeat were phylogenetically related. However, nine of these species belong to the phylogenetically derived clade including the M. sativa and M. arborea complexes.

Conclusions

The use of the E180 family as a phylogenetic marker in Medicago should be viewed with caution. Its amplification appears to have been produced through recurrent and independent evolutionary episodes in both annual and perennial Medicago species as well as in basal and derived clades.     

Intestinal protozoan infections and echinococcosis in the inhabitants of Dornod and Selenge, Mongolia (2003)

The status of intestinal parasitic infections and seroprevalence of cystic echinococcosis in the inhabitants in Dornod and Selenge, Mongolia, was observed with stool and serum samples from 165 and 683 residents from August 9 to August 15, 2003. A total of 10 inhabitants (6.1%) were found to be infected with protozoan cysts or oocysts by stool examinations; 7, 1 and 2 cases with Entamoeba coli, Giardia lamblia and Cryptosporidium parvum, respectively. A total of 62 people (9.1%) revealed significantly high levels of specific antibodies against Echinococcus granulosus by enzyme-linked immunosorbent assay (ELISA). The surveyed areas are rural areas and the sanitized tab water is not available. There is a possibility of endemic transmission of water-borne protozoan diseases in these areas. The clinical echinococcosis is needed to be searched from the seropositive inhabitants.     

Taenia crassiceps: energetic and respiratory metabolism from cysticerci exposed to praziquantel and albendazole in vitro

Praziquantel prevents glucose uptake, influencing energy metabolism, while albendazole selectively inhibits the uptake of glucose, leading to glycogen storage depletion in the parasite. The objective of this study was to determine the concentrations of glucose and organic acids related to energy and respiratory metabolisms in in vitroTaenia crassiceps cysticerci in the initial, larval and final stages exposed to sub lethal dosages of anti-helminthic drugs. Spectrophotometric and chromatographic analysis were performed to detect glucose, lactate, oxaloacetate, citrate, malate, fumarate and succinate secreted/excreted by in vitro cysticerci with 0.03 and 0.06 μg/mL of praziquantel and 0.05 and 0.075 μg/mL of albendazole. The anti-helminthic drugs decreased the excretion of lactate and induced aerobic energy pathways. Concentrations of glucose remained unaltered confirming blockage of its uptake.     

Morphologic and genetic identification of Taenia tapeworms in Tanzania and DNA genotyping of Taenia solium

Species identification of Taenia tapeworms was performed using morphologic observations and multiplex PCR and DNA sequencing of the mitochondrial cox1 gene. In 2008 and 2009, a total of 1,057 fecal samples were collected from residents of Kongwa district of Dodoma region, Tanzania, and examined microscopically for helminth eggs and proglottids. Of these, 4 Taenia egg positive cases were identified, and the eggs were subjected to DNA analysis. Several proglottids of Taenia solium were recovered from 1 of the 4 cases. This established that the species were T. solium (n = 1) and T. saginata (n = 3). One further T. solium specimen was found among 128 fecal samples collected from Mbulu district in Arusha, and this had an intact strobila with the scolex. Phylegenetic analysis of the mtDNA cox1 gene sequences of these 5 isolates showed that T. saginata was basal to the T. solium clade. The mitochondrial cox1 gene sequences of 3 of these Tanzanian isolates showed 99% similarity to T. saginata, and the other 2 isolates showed 100% similarity to T. solium. The present study has shown that Taenia tapeworms are endemic in Kongwa district of Tanzania, as well as in a previously identified Mbulu district. Both T. solium isolates were found to have an "African/Latin American" genotype (cox1).     

Current Status of Taeniasis in Thailand

Taeniasis is prevalent in all regions of Thailand, except the South. Infections were more frequently found in males than females of any age from 7-83 years. Taenia saginata is the most common species throughout the country. Taenia asiatica was reported only in the province of Kanchanaburi in the Central region. Co-infections, with Taenia solium and T. asiatica or T. solium and T. saginata, were found. Hybridization between T. asiatica and T. saginata is evidence that co-infection is never found between these 2 species. Finding more than 1 worm in a single patient was not entirely rare. Genetic variation was found without correlation to its geographic distribution in T. saginata, whereas no variation was found in T. asiatica.     

Taenia asiatica: the Most Neglected Human Taenia and the Possibility of Cysticercosis

Not only Taenia solium and Taenia saginata, but also Taenia asiatica infects humans. The last species is not included in the evaluation of the specificity of the immunodiagnostic techniques for taeniasis/cysticercosis. There is currently no specific immunodiagnostic method for T. asiatica available. Therefore, due to the fact that molecular techniques (the only tool to distinguish the 3 Taenia species) are normally not employed in routine diagnostic methods, the 2 questions concerning T. asiatica (its definite geographic distribution and its ability to cause human cysticercosis), remain open, turning T. asiatica into the most neglected agent of human taeniasis-cysticercosis.     

Evidence for Tissue-Specific JAK/STAT Target Genes in Drosophila Optic Lobe Development

The evolutionarily conserved JAK/STAT pathway plays important roles in development and disease processes in humans. Although the signaling process has been well established, we know relatively little about what the relevant target genes are that mediate JAK/STAT activation during development. Here, we have used genome-wide microarrays to identify JAK/STAT targets in the optic lobes of the Drosophila brain and identified 47 genes that are positively regulated by JAK/STAT. About two-thirds of the genes encode proteins that have orthologs in humans. The STAT targets in the optic lobe appear to be different from the targets identified in other tissues, suggesting that JAK/STAT signaling may regulate different target genes in a tissue-specific manner. Functional analysis of Nop56, a cell-autonomous STAT target, revealed an essential role for this gene in the growth and proliferation of neuroepithelial stem cells in the optic lobe and an inhibitory role in lamina neurogenesis.     

Snail family members and cell survival in physiological and pathological cleft palates

Palate fusion is a complex process that involves the coordination of a series of cellular changes including cell death and epithelial to mesenchymal transition (EMT). Since members of the Snail family of zinc-finger regulators are involved in both triggering of the EMT and cell survival, we decided to study their putative role in palatal fusion. Furthermore, Snail genes are induced by transforming growth factor beta gene (TGF-beta) superfamily members, and TGF-beta(3) null mutant mice (TGF-beta(3)-/-) show a cleft palate phenotype. Here we show that in the wild-type mouse at the time of fusion, Snail is expressed in a few cells of the midline epithelial seam (MES), compatible with a role in triggering of the EMT in a small subpopulation of the MES. We also find an intriguing relationship between the expression of Snail family members and cell survival associated to the cleft palate condition. Indeed, Snail is expressed in the medial edge epithelial (MEE) cells in TGF-beta(3)-/-mouse embryo palates, where it is activated by the aberrant expression of its inducer, TGF-beta(1), in the underlying mesenchyme. In contrast to Snail-deficient wild-type pre-adhesion MEE cells, Snail-expressing TGF-beta(3) mutant MEE cells survive as they do their counterparts in the chick embryo. Interestingly, Slug is the Snail family member expressed in the chick MEE, providing another example of interchange of Snail and Slug expression between avian and mammalian embryos. We propose that in the absence of TGF-beta(3), TGF-beta(1) is upregulated in the mesenchyme, and that in both physiological (avian) and pathological (TGF-beta(3)-/-mammalian) cleft palates, it induces the expression of Snail genes promoting the survival of the MEE cells and permitting their subsequent differentiation into keratinized stratified epithelium.