Dipetalonema viteae: Phosphorylcholine and non-phosphorylcholine antigenic determinants in infective larvae and adult worms

Gualzata, M.; Weiss, N.; Heusser, C H

doi:10.1016/0014-4894(86)90139-6

Cited by 38 publications

(17 citation statements)

References 17 publications

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“…A major post-translational modification of parasitic helminth antigens is apparently PC. This antigenic determinant has been detected in nematodes (5,8,34,35), in trematodes, including Schistosoma mansoni (9), and in the cestode Bothriocephalus scorpii (36). In fact, the frequency of serological cross-reactivity between cestodes, trematodes and, in particular, nematodes (37) may be accounted for by the broad distribution of PCbearing molecules.…”

Section: Discussionmentioning

confidence: 99%

Structural Elucidation and Monokine-inducing Activity of Two Biologically Active Zwitterionic Glycosphingolipids Derived from the Porcine Parasitic Nematode Ascaris suum

Lochnit¹,

Dennis²,

Ulmer³

et al. 1998

Journal of Biological Chemistry

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The isolated neutral glycosphingolipid fraction from the pig parasitic nematode, Ascaris suum, was fractionated by silica gel chromatography to yield a neutral and a zwitterionic glycosphingolipid fraction, the latter of which mainly contained two zwitterionic glycosphingolipids termed components A and C. Preliminary chemical characterization with hydrofluoric acid treatment and immunochemical characterization with a phosphocholine-specific monoclonal antibody indicated that both components contained phosphodiester substitutions: phosphocholine for component A, and phosphocholine and phosphoethanolamine for component C. Both components were biologically active in inducing human peripheral blood mononuclear cells to release the inflammatory monokines tumor necrosis factor ␣, interleukin 1, and interleukin 6. Component A was the more bioactive molecule, and its biological activity was abolished on removal of the phosphocholine substituent by hydrofluoric acid. The glycosphingolipid components were structurally analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, liquid secondary ion mass spectrometry, methylation analysis, 1 H NMR spectroscopy, exoglycosidase cleavage, and ceramide analysis. Their chemical structures were elucidated to be (see Structure I below), The carbohydrate moiety oligosaccharide core was characterized as belonging to the arthro series of protostomial glycosphingolipids. The ceramide moiety was distinguished by (R)-2-hydroxytetracosanoic acid as the dominant fatty acid species and by the C17 iso-branched sphingosine and sphinganine bases, 15-methylhexadecasphing-4-enine and 15-methylhexadecasphinganine, respectively.Analyses of the immunoreactivity between neutral fraction glycolipids derived from various species of parasitic nematodes have indicated a high degree of serological cross-reactivity (1, 2). The structural basis for this immunological cross-reactivity between parasitic nematodes at the level of glycolipids is at present unknown. Structural studies on the neutral fraction glycosphingolipids from adults of the porcine parasitic nematode Ascaris suum have revealed that the identified arthro series oligosaccharide chain was not immunogenic, i.e. did not exhibit immunoreactivity toward infection sera from A. suuminfected mice (2, 3). However, a zwitterionic glycosphingolipid fraction was also isolated from A. suum that demonstrated a phosphodiester sidechain as a structural modification of possibly phosphocholine (PC) 1 and phosphoethanolamine (PE). In addition, these zwitterionic glycolipids were immunogenic/antigenic, i.e. exhibited immunoreactivity toward infection sera from A. suum-infected mice (2).PC-containing macromolecules have been regularly detected * This project was supported by the Deutsche Forschungsgemeinschaft (SFB 535 and Graduiertenkolleg Molecular Biology and Pharmacology) and by the Bundesministerium fü r Bildung, Wissenschaft, Forschung und Technologie Grant 01 KI 9471. The costs of publication of this article were defrayed in...

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Section: Discussionmentioning

confidence: 99%

Structural Elucidation and Monokine-inducing Activity of Two Biologically Active Zwitterionic Glycosphingolipids Derived from the Porcine Parasitic Nematode Ascaris suum

Lochnit¹,

Dennis²,

Ulmer³

et al. 1998

Journal of Biological Chemistry

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“…However, it would be a mistake to ignore nonpeptide antigens. An important nonprotein component expressed by filarial nematodes is phosphorylcholine (115–117), which is secreted by adult filariae (116) and forms the basis for the first circulating antigen test for bancroftian filariasis.…”

Section: A Broader Immunological Profile Of Filariaementioning

confidence: 99%

Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity

Maizels

Blaxter

Scott

2001

Parasite Immunology

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Filarial nematodes are metazoan parasites with genome sizes of> 100 million base pairs, probably encoding 15 000-20 000 genes. Within this considerable gene complement, it seems likely that filariae have evolved a spectrum of immune evasion products which underpin their ability to live for many years within the human host. Moreover, no suitable vaccine currently exists for human filarial diseases, and few markers have yet been established for diagnostic use. In this review, we bring together biochemical and immunological data on prominent filarial proteins with the exciting new information provided by the Filarial Genome Project's expressed sequence tag (EST) database. In this discussion, we focus on those genes with the highest immunological profile, such as inhibitors of host enzymes, cytokine homologues and stage-specific surface proteins, as well as products associated with the mosquito-borne infective larva which offer the best opportunity for an anti-filarial vaccine. These gene products provide a fascinating glimpse of the molecular repertoire which helminth parasites have evolved to manipulate and evade the mammalian immune response.

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“…These assays are not specific for lymphatic filariasis, however, as the monoclonal antibodies utilized to trap serum antigen were subsequently determined to be directed against phosphocholine epitopes (72). Phosphocholine is found in several other infectious agents (50,107). Other antigens such as those shared with the dog heartworm Dirofilaria immitis have also been tested in the field (140), but to date none have proven to be both specific and sensitive enough for general use.…”

Section: Serologic Assaysmentioning

confidence: 99%

Clinical and laboratory aspects of filariasis

Nanduri

Kazura

1989

Clin Microbiol Rev

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Human filarial infections afflict over 150 million persons worldwide and are major causes of morbidity in many developing countries. Onchocerca volvulus infection is a leading preventable cause of blindness, while bancroftian and brugian filariasis may produce lymphatic obstruction of the genitalia and extremities (elephantiasis). Definitive diagnosis of these helminthic infections currently depends on demonstration of microfilariae in host tissues, i.e., the skin in the case of O. volvulus and the bloodstream in the cases of Wuchereria bancrofti and Brugia malayi. Many investigations are now directed at developing specific and sensitive serum antigen assays that will allow diagnosis of active infection (i.e., presence of adult-stage parasites) in the absence of detectable microfilariae. With respect to the immunology of these parasitic infections, efforts are being directed at elucidating the role of T- and B-cell responses in the development of pathologic lesions and resistance to reinfection. These data as well as molecular biologic approaches to identify and study filarial molecules which are immunogenic are discussed. Finally, since treatment of filariases at present depends on antiparasitic drugs, the clinical indications and dosages of diethylcarbamazine and ivermectin are summarized.

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Dipetalonema viteae: Phosphorylcholine and non-phosphorylcholine antigenic determinants in infective larvae and adult worms

Cited by 38 publications

References 17 publications

Structural Elucidation and Monokine-inducing Activity of Two Biologically Active Zwitterionic Glycosphingolipids Derived from the Porcine Parasitic Nematode Ascaris suum

Structural Elucidation and Monokine-inducing Activity of Two Biologically Active Zwitterionic Glycosphingolipids Derived from the Porcine Parasitic Nematode Ascaris suum

Immunological genomics of Brugia malayi: filarial genes implicated in immune evasion and protective immunity

Clinical and laboratory aspects of filariasis

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