Prostaglandin E2 as a Cestodes immunomodulator (original) (raw)
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The spectrum of immunomodulating molecules produced by tapeworms is not yet well understood. The aims of this study, on the tapeworm Diphyllobothrium dendriticum, were: 1) detection and quantifica-tion of prostaglandins (PGs) E 2 and D 2 by high performance liquid chromatography; 2) visualization of PGE 2 and PGD 2 in specific cells, using methods of immunocytochemistry and confocal laser scanning microscopy; and 3) investigation of the ultrastructure of the cells potentially producing PGE 2 and PGD 2. The PGE 2 immunoreaction (IR) was found in the apical terminals of the frontal glands and sensory organs in the tegument and in small neurons belonging to the main cords and commissures. PGE 2-IR partly coincided with-tubulin-IR. PGD 2-IR occurred in the muscle fibers of longitudinal and transverse body muscles and coincided with phalloidin TRITC staining. Both PGE 2 and PGD 2 were found in the flame cells of the excretory system. Ultrastructural study of the tegument revealed two types of structures that potentially produce PGE 2 : ciliated and unciliated free nerve endings and frontal gland terminals reinforced with neurotubules. In the main nerve cords, small neurons were identified as potentially exhibiting PGE 2-immunoreactivity. In homogenates of the plerocercoids, the measured content of PGE 2 and PGD 2 was 33.15 ng mg −1 and 1.94 ng mg −1 of fresh tissue weight, respectively. We found evidence of PGE 2 and PGD 2 in D. dendriticum parasitizing Coregonus autumnalis (fish) and proved excretion of PGE 2 and PGD 2 in response to C. autumnalis blood serum. Prostaglandins produced by D. dendriticum probably play a dual role: 1) PGE 2 and PGD 2 potentially modulate the fish antiparasitic immune response; 2) PGE 2 is presumably necessary for proper development and function of the nervous system, and PGD 2 can act as an antagonist against mediators causing muscle contraction.
Using immunofluorescence methods, for the first time distribution of the host immunity regulator – prostaglandin E2 in the organism of the tapeworm Diphyllobothrium dendriticum was revealed. PG E2-like immunoreactivity (IR) was revealed in large cells is situated in the zone of the cortical parenchyma and also in drop-shaped dilatations on the surface of tegument’s ectal cytoplasm. Overlapping areas of IR to PG E2 and to acetylated tubuline was revealed. PG E2-like-IR areas is situated within α-tubuline-IR areas and occupy the lesser space when compared with them. With respect to distribution and a number of morphological features, PG E2-like- and α-tubuline-IR elements conform to frontal glands, excreting secreta on the surface of the tegument through own specialized ducts. Therefore, the glands have immunomodulatory function, synthesizing and excreting prostaglandin Е2 into host tissues.
Many helminth parasites have evolved strategies to evade the immune response of their hosts, which includes immunomodulation. Prostaglandin E2 (PGE2) is one of the best-described immunomodulators in mammalian helminth parasite infections. We hypothesized that also in teleost fish anti-helminthic immune responses are regulated via PGE2. We used a model system consisting of the tapeworm Schistocephalus solidus and its host, the three-spined stickleback (Gasterosteus aculeatus), to investigate in vitro effects of PGE2 on head kidney leucocytes (HKL) derived from sticklebacks that were experimentally infected with S. solidus. PGE2 was tested alone or in combination with either S. solidus antigens or bacterial lipopolysaccharides (LPS). After in vitro culture, cell viability and changes in leucocyte subpopulations (granulocytes to lymphocytes ratios) were monitored by flow cytometry and HKL were tested for their capacity to produce reactive oxygen species (ROS) with a chemiluminescence assay. In short term (2 h) HKL cultures PGE2 did not change the total numbers of live HKL, but the production of ROS decreased significantly with high (0.1 mmol L1) PGE2 concentrations. In long-term (96 h) cultures high PGE2 concentrations induced a sharp decrease of leucocytes viability, while low (0.1 pmol L1) and intermediate (0.1 nmol L1) concentrations of PGE2 caused elevated leucocyte viability compared to controls. This coincided with reduced ROS production in cultures with high PGE2 and elevated ROS production in cultures with low PGE2. Granulocyte to lymphocyte ratios increased with high PGE2 concentrations alone and in combination with S. solidus antigens and LPS, most prominently with HKL from S. solidus infected sticklebacks. The present study supports the hypothesis that PGE2 might be an immunomodulator in tapewormefish parasiteehost interactions.
"N. M. Biserova and I. A. Kutyrev Biology Bulletin, 2014, Vol. 41, No. 3, pp. 242–250 For the first time, the potential immunomodulators prostaglandin E2 and γaminobutyric acid (GABA) have been revealed in the plerocercoid Diphyllobothrium dendriticum, which is a parasite in the tis sues and abdominal cavity of the Baikal omul Coregonus migratorius. The localization of immunomodulators in parasite tissues was compared with the location of typical markers of the nervous system (serotonin (5HT) and FMRFamide) and a marker of microtubules (αtubulin). Prostaglandin E2 was revealed in the cells that are immunoreactive to αtubulin and are situated in the cortical parenchyma outside the central nervous sys tem (CNS). It is supposed that prostaglandin E2 is produced by the frontal glands and is carried out onto the tegument surface through specialized ducts. Immunoreaction to GABA was revealed in the central and peripheral nervous systems. GABAergic neurosomes, the neurites of which form a net on the surface of mus cle layers and in the subtegument, were revealed in the cerebral ganglion and main nerve cords. The morpho logical characteristics for the identification of serotoninergic neurons in the CNS were described."
The FASEB Journal, 2016
Clinical trials have shown that administration of the nematode Trichuris suis can be beneficial in treating various immune disorders. To provide insight into the mechanisms by which this worm suppresses inflammatory responses, an active component was purified from T. suis soluble products (TsSPs) that suppress TNF and IL-12 secretion from LPS-activated human dendritic cells (DCs). Analysis by liquid chromatography tandem mass spectrometry identified this compound as prostaglandin (PG)E2. The purified compound showed similar properties compared with TsSPs and commercial PGE2 in modulating LPS-induced expression of many cytokines and chemokines and in modulating Rab7B and P2RX7 expression in human DCs. Furthermore, the TsSP-induced reduction of TNF secretion from DCs is reversed by receptor antagonists for EP2 and EP4, indicating PGE2 action. T. suis secretes extremely high amounts of PGE2 (45-90 ng/mg protein) within their excretory/secretory products but few related lipid mediators as established by metabololipidomic analysis. Culture of T. suis with several cyclooxygenase (COX) inhibitors that inhibit mammalian prostaglandin synthesis affected the worm's motility but did not inhibit PGE2 secretion, suggesting that the worms can synthesize PGE2 via a COX-independent pathway. We conclude that T. suis secretes PGE2 to suppress proinflammatory responses in human DCs, thereby modulating the host's immune response.-Laan, L.
Eicosanoids in parasites and parasitic infections
Advances in parasitology, 2000
Eicosanoids are lipid mediators with multiple functions in vertebrate tissues and invertebrate organisms. In this review the roles of eicosanoids--mostly prostaglandins (PGs), thromboxanes and leukotrienes--in parasite physiology and host-parasite interactions are discussed. PGs are present in the saliva of blood-sucking arthropods facilitating feeding by increasing local blood flow and prolonged attachment of ticks by immune suppression. Release of various eicosanoids has also been demonstrated for a number of protozoan and metazoan endoparasites. These substances appear to play a role in penetration, immune suppression, inflammation or modulation of haemostasis, enabling parasite invasion and establishment. Moreover, endogenous eicosanoids serve various functions in parasite metabolism and physiology. In many parasitic infections eicosanoids are involved in host pathology, e.g. granuloma formation, coagulopathy, secretory diarrhoea, or fever. Immune suppression by induction of PG ...
Evaluation of an innate immune reaction to parasites in earthworms
Journal of Invertebrate Pathology, 2004
Encapsulation is an essential process of the invertebrate immune system and includes the prophenoloxidase (proPO) cascade. We present an assay for evaluating this immune response, now newly adapted to earthworms. Coelomic fluid is withdrawn and coelomocytes are stained with L L-Dopa. We studied assay repeatability and the correlation between number of PO-active cells and infection level of the parasitic protozoan Monocystis sp. in the earthworm Lumbricus terrestris. Our study showed high assay repeatability although the expected negative relationship between PO-active coelomocytes and parasite load was not observed; yet a suggestion toward a positive relationship was detected. This finding is contrary to previous assumptions that presume coelomocyte concentrations to be the independent variable determining parasite load.
The cytomorphological and biochemical composition of the blood has been studied for the deep dwelling (bottom) morphotype of the Baikal omul infected by plerocercoids of Diphyllobothrium dendriticum, during the fish spawning migration. A decrease in hemoglobin synthesis and an increase in the proliferative activity of erythroid cells have been registered. The changes in the leukocyte population composition, immu noglobulin, and total protein concentrations evidenced a disorder of blood cell proliferation and differentia tion and suppression of the immune response in the infected fish. The changes in the humoral and cell factors of homeostasis in Coregonus migratorius infected by D. dendriticum during the spawning period remain within the limits of the adaptive possibilities of the species.
Journal of Fish Diseases, 2007
The pathological changes induced by an infection of Diphyllobothrium dendriticum (Nitzsch, 1824) plerocercoids in powan, Coregonus lavaretus (L.), from Loch Lomond, Scotland, were assessed using immunohistochemical and ultrastructural techniques. In a sample of 26 powan, the occurrence of encysted plerocercoids of D. dendriticum on the outer surface of the stomach was 38.5% (n = 10) with the number of cysts ranging from 4 to 15 and measuring 4.2 AE 1.0 mm · 3.4 AE 0.9 mm (mean AE SD). Histological examination of intestinal samples also revealed plerocercoids (2-21) encapsulated within a proliferation of mesenteric fibrous tissues of the gastric wall and, occasionally, by the gut lamina propria-submucosa and lamina muscularis. In section, cysts were tri-layered and were formed from a series of concentric whorls of fibroblast and collagen fibre-based connective elements. The extent of necrosis within each muscle layer and the serosa of the stomach differed, notably within the latter that was marked by a chronic inflammatory reaction and fibrosis. Within the cyst and around it, a large number of degranulating mast cell/eosinophilic granule cells were seen, in addition to melano-macrophage centres. Immunohistochemical staining of sections of infected stomach revealed a high density of elements, in close proximity to plerocercoids, staining positive for serotonin, bombesin, substance P and galanin.