Pathology Of Schistosomiasis Research Articles

Identification of an alpha3-fucosyltransferase and a novel alpha2-fucosyltransferase activity in cercariae of the schistosome Trichobilharzia ocellata: biosynthesis of the Fucalpha1-->2Fucalpha1-->3[Gal(NAc)beta1-->4]GlcNAc sequence.

Fucose is a major constituent of the protein- and lipid-linked glycans of the various life-cycle stages of schistosomes. These fucosylated glycans are highly antigenic and seem to play a role in the pathology of schistosomiasis. In this article we describe the identification and characterization of two fucosyltransferases (FucTs) in cercariae of the avian schistosome Trichobilharzia ocellata, a GDP-Fuc:[Galbeta1-->4]GlcNAcbeta-R alpha1-->3-FucT and a novel GDP-Fuc:Fucalpha-R alpha1-->2-FucT. Triton X-100 extracts of cercariae were assayed for FucT activity using a variety of acceptor substrates. Type 1 chain (Galbeta1-->3GlcNAc) based compounds were poor acceptors, whereas those based on a type 2 chain (Galbeta1-->4GlcNAc), whether alpha2'-fucosylated, alpha3'-sialylated, or unsubstituted, and whether present as oligosaccharide or contained in a glycopeptide or glycoprotein, all served as acceptor substrates. In this respect the schistosomal alpha3-FucT resembles human FucT V and VI rather than other known FucTs. N-ethylmaleimide, an inhibitor of several human FucTs, had no effect on the activity of the schistosomal alpha3-FucT, whereas GDP-beta-S was strongly inhibitory. Large scale incubations were carried out with Galbeta1-->4GlcNAc, GalNAcbeta1-->4GlcNAcbeta-O -(CH2)8COOCH3 and Fucalpha1-->3GlcNAcbeta1-->2Man as acceptor substrates and the products of the incubations were isolated using a sequence of chromatographic techniques. By methylation analysis and 2D-TOCSY and ROESY1H-NMR spectroscopy the products formed were shown to be Galbeta1-->4[Fucalpha1-->2Fucalpha1-->3]GlcNAc, GalNAcbeta1-->4[Fucalpha1-->2Fucalpha1-->3]GlcNAcbe ta-O-(CH2)8COOCH3, and Fucalpha1-->2Fucalpha1-->3GlcNAcbeta1-->2Man, respectively. It is concluded that the alpha2-FucT and alpha3-FucT are involved in the biosynthesis of the (oligomeric) Lewisx sequences and the Fucalpha1-->2Fucalpha1-->3GlcNAc structural element that have been described on schistosomal glycoconjugates.

CD4+ T cell-mediated granulomatous pathology in schistosomiasis is downregulated by a B cell-dependent mechanism requiring Fc receptor signaling.

The effector functions of CD4+ T lymphocytes are generally thought to be controlled by distinct populations of regulatory T cells and their soluble products. The role of B cells in the regulation of CD4-dependent host responses is less well understood. Hepatic egg granuloma formation and fibrosis in murine schistosomiasis are dependent on CD4+ lymphocytes, and previous studies have implicated CD8+ T cells or cross-regulatory cytokines produced by T helper (Th) lymphocytes as controlling elements of this pathologic process. In this report, we demonstrate that B cell-deficient (muMT) mice exposed to Schistosoma mansoni develop augmented tissue pathology and, more importantly, fail to undergo the spontaneous downmodulation in disease normally observed during late stages of infection. Unexpectedly, B cell deficiency did not significantly alter T cell proliferative response or cause a shift in the Th1/Th2 balance. Since schistosome-infected Fc receptor-deficient (FcR gamma chain knockout) mice display the same exacerbated egg pathology as that observed in infected muMT mice, the B cell- dependent regulatory mechanism revealed by these experiments appears to require receptor-mediated cell triggering. Together, the data demonstrate that humoral immune response/FcR interactions can play a major role in negatively controlling inflammatory disease induced by CD4+ T cells.

Cellular immune response and pathology in schistosomiasis.

In the present review, some aspects of the cellular response following the murine Schistosoma mansoni infection are described. Due to the peculiar route used by the schistosome to infect its definitive host, the skin appears as a critical site in which the initial events of the host/parasite relationship occur and where the immune response is initiated. Moreover, the induction and the modulation of the granuloma formation, which represent the main aspect of the pathology of this parasitic disease, is under the control of several cellular populations n which CD4 and CD8 T cells play a key role. The cytokines produced in response to the parasite, such as IL7 in the skin and IFN gamma in the liver, seem to influence the further development of immunity against Schistosoma mansoni.

IL-12-based vaccine prevents pathology of schistosomiasis

IL-12-based vaccine prevents pathology of schistosomiasis

Identification ofSchistosoma haematobium soluble egg antigens that elicit human granuloma formation in vitro

Schistosoma haematobium soluble egg antigens (SH SEAs) induce intense granulomas in human hosts that often culminate in severe disease. In an attempt to identify the SH SEA fractions that are responsible for pathology, we combined T-cell Western blotting and an in vitro model of granuloma formation. Whole SH SEAs were dotted onto nitrocellulose pieces or were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and electrotransferred onto nitrocellulose paper. Horizontal strips bearing the separated antigens were solubilized in dimethylsulfoxide and precipitated in carbonate/bicarbonate buffer. Antigen-free and antigen-bearing particles were used to stimulate peripheral blood mononuclear cells (PBMCs) obtained from S. haematobium-infected patients and sex- and age-matched healthy controls to form granulomas in vitro. Whole SH SEA-bearing nitrocellulose particles elicited in vitro formation of granulomas by PBMCs from infected donors. The response was similar in sensitivity, specificity, and reproducibility to that evoked by SH SEA-bound polyacrylamide beads. The results obtained in samples form 30 patients and 10 controls tested with SH SEA-separated fractions revealed that SEA bands of 84,000, 63,000, 57,000, 55,000, 40,000, 30,000, and 28,000 Da elicited in vitro granuloma reactions by PBMCs of almost all infected patients. Conversely, separated soluble adult-worm antigens failed to stimulate PBMCs of infected patients to form granulomas. This study is the first to identify the SH SEA fractions that evoke in vitro granuloma formation and represents an initial step toward the development of an anti-urinary schistosomiasis pathology vaccine.

Regulation of gene expression in the Schistosoma mansoni female.

The maturation of females of S. mansoni is a process which depends on the presence of male parasites. Preliminary results indicated that the males may secret hormones, possibly steroid or steroid-like compounds, which regulate the expression of genes directly connected to events pertaining to oogenesis. Because the eggs are important agents in the pathology of schistosomiasis, it is of interest to elucidate the biochemical events associated to this developmental stage. The present work describes the efforts to characterize proteins which regulate the expression of a gene encoding a major protein precursor of egg shells and which is only transcribed by adult females. It is hoped that the receptor for the male hormone will be detected among these regulatory proteins.

Pathology of Schistosomiasis mansoni in rabbits

The pathology of schistosomiasis mansoni in rabbits was studied with special consideration to worm burden and duration of infection. Heavy and prolonged infections resulted in severe changes involving the intrahepatic portal vein branches, such as: polypoid endophlebitis, granulomatous endophlebitis and, later on, vascular occlusion and recanalization, vascular ectasia, fibrosis and hyalinization of the endothelial polyps. Living and dead adult worms, rather than the mature eggs, were the main pathogenetic factors. For some time the lesions tend to be limited to the portal vein branches, not extending to the periportal tissues, but, after 8 to 10 months, variable degree of portal, septal and intra-parenchymal fibrosis can be formed. However, both vascular and fibrotic changes in the liver had a focal distribution and therefore did not appear to cause portal hypertension and had no resemblance to the human pathology seen in cases of hepatosplenic schistosomiasis. Pathology of schistosomiasis in rabbits has peculiar aspects, which are worthwhile studying, since the model can be of interest for investigations, especially concerning the immunology and immunopathology of schistosomiasis mansoni.

The changing pattern of pathology due to Schistosoma mansoni infection.

A survey of the autopsy data on hepatosplenic schistosomiasis during periods, before and after the advent of new chemotherapeutic drugs, revealed that: a) the pathological presentation was the same for the two periods; b) the number of cases in the last five years is progressively decreasing; c) hepatosplenic disease due to schistosomiasis is becoming rare in young people. These data represent a change in the pattern of pathology in schistosomiasis, probably related to new chemotherapy.

The pathology, pathobiology and pathogenesis of schistosomiasis

Although the general pathology of schistosomiasis has been well understood for more than 70 years, it is only recently that it has been possible to analyse the disease at the molecular level and to understand the relationship between the number of parasites in an infected individual and the appearance of overt disease.

The pathology of schistosomiasis in Ibadan, Nigeria with special reference to the appendix, brain, pancreas and genital organs

Journal Article The pathology of schistosomiasis in Ibadan, Nigeria with special reference to the appendix, brain, pancreas and genital organs Get access G.M. Edington, G.M. Edington ∗Department of Human Pathology, Ahmadu Bello University, Zaria, Nigeria Search for other works by this author on: Oxford Academic PubMed Google Scholar I. Nwabuebo, I. Nwabuebo Search for other works by this author on: Oxford Academic PubMed Google Scholar T.A. Junaid T.A. Junaid Search for other works by this author on: Oxford Academic PubMed Google Scholar Transactions of The Royal Society of Tropical Medicine and Hygiene, Volume 69, Issue 1, 1975, Pages 153–162, https://doi.org/10.1016/0035-9203(75)90027-9 Published: 01 January 1975

Schistosoma mansoni Infections in Cercopithecus sabaeus Monkeys

Cercopithecus sabaeus (green) monkeys discharged eggs up to 3.5 years after initial exposure and for a comparable period after reexposure. The number and development of worms from challenge infections were similar to initial infections, but excretion of eggs was delayed after challenge. Monkeys exposed repeatedly to moderate or small numbers of cercariae tolerated a burden of worms that would have been lethal as a single initial infection. There was evidence that worms lived for 5 years, and without regression in size. Large accumulations of eggs still occurred in the liver and intestine after 5 years, and the relative numbers of immature, mature, and degenerate eggs were similar to early stages of first infections. The response of the green monkey to S. mansoni is in marked contrast to that of Macaca mulatta, which suppresses excretion of eggs after 6 to 9 months and quickly acquires strong resistance to challenge infections. The longer output of eggs by the green monkey is more like what occurs in man. A corresponding comparison of acquired resistance is not possible because too little is known about resistance imposed against schistosomes in the human host. The rhesus and the green monkeys may provide a valuable experimental model for investigating the immune mechanism against schistosomes. The green monkey may be useful in the evaluation of schistosomicidal drugs. The need for experimental hosts of human schistosomes that react to the infections more like man than the commonly used Macaca mulatta (rhesus) monkey was emphasized by Sadun et al. (1966a). Their studies and those of Sadun and Bruce (1964) on the biology and pathology of schistosomiasis in 10 species of primates showed that worm recovery rates were highest in three species of Macaca, but self-cure occurred within a few months. The baboon and chimpanzee discharged eggs for much longer periods, but worm recovery was relatively low. For other species, the infections were abortive from the beginning. Only the chimpanzee developed pipe-stem fibrosis of the liver. The need for information on other primate hosts was noted by the above authors. Information on acquired resistance among primate hosts is essentially limited to the rhesus monkey. For man, too little is known to recognize a suitable model. The current study is concerned with another primate, Cercopithecus sabaeus, the green Received for publication 22 May 1967. * Assigned to Walter Reed Army Institute of Research, Washington, D. C. (20012), with duty station at the Department of Preventive and Social Medicine, University of Ibadan, Ibadan, Nigeria. t Present address: Tropical Disease Section, Ecological Investigations Program, Communicable Disease Center, U. S. Public Health Service, San Juan, Puerto Rico. monkey, and includes observations on the length of the prepatent period, duration and pattern of egg discharge, life-span of the infection, distribution and condition of eggs in tissues, and acquired resistance. These objectives were not all completed as originally planned, due to closing of this laboratory. A number of investigators have exposed the green monkey to human schistosomes for limited objectives, and only a few animals were involved, or the infections were of short duration (Archibald, 1923; Black, 1932; Vogel and Minning, 1953; Kuntz, 1955; Vogel, 1962; Hsii and Hsii, 1962; Meisenhelder and Thompson, 1963; and Ritchie et al., 1964). The green monkey was found to discharge eggs for relatively long periods. In contrast to M. mulatta, challenge infections developed to maturity in animals that had been infected

The relative susceptibilities of the commonly-used laboratory mammal to infection by Schistosoma mansoni.

The relative susceptibilities of the commonly-used laboratory mammal to infection by Schistosoma mansoni.

Observations on the pathology of schistosomiasis (S. hæmatobium and S. mansoni) in the human subject

Observations on the pathology of schistosomiasis (<i>S. hæmatobium</i> and <i>S. mansoni</i>) in the human subject