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Titolo:
Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus
Autore:
Schonemeyer, A; Lucius, R; Sonnenburg, B; Brattig, N; Sabat, R; Schilling, K; Bradley, J; Hartmann, S;
Indirizzi:
Humboldt Univ, Dept Mol Parasitol, Inst Biol, Charite Med Sch, D-10115 Berlin, Germany Humboldt Univ Berlin Germany D-10115 te Med Sch, D-10115 Berlin, Germany Humboldt Univ, Charite Med Sch, Inst Med Immunol, Berlin, Germany HumboldtUniv Berlin Germany Med Sch, Inst Med Immunol, Berlin, Germany Bernhard Nocht Inst Trop Med, Div Clin Chem, Hamburg, Germany Bernhard Nocht Inst Trop Med Hamburg Germany lin Chem, Hamburg, Germany Univ Jena, Inst Biochem, D-6900 Jena, Germany Univ Jena Jena Germany D-6900 v Jena, Inst Biochem, D-6900 Jena, Germany Univ Salford, Dept Biol Sci, Manchester, Lancs, England Univ Salford Manchester Lancs England ol Sci, Manchester, Lancs, England
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 6, volume: 167, anno: 2001,
pagine: 3207 - 3215
SICI:
0022-1767(20010915)167:6<3207:MOHTCR>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
MHC CLASS-II; GROWTH-FACTOR-BETA; NECROSIS-FACTOR-ALPHA; HUMAN CYSTATIN-C; CYSTEINE PROTEINASES; ANTIGEN PRESENTATION; CHICKEN CYSTATIN; CATHEPSIN-B; INTERLEUKIN-10 PRODUCTION; PERITONEAL-MACROPHAGES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
60
Recensione:
Indirizzi per estratti:
Indirizzo: Hartmann, S Humboldt Univ, Dept Mol Parasitol, Inst Biol, Charite Med Sch,Philippstr 13, D-10115 Berlin, Germany Humboldt Univ Philippstr 13 BerlinGermany D-10115 n, Germany
Citazione:
A. Schonemeyer et al., "Modulation of human T cell responses and macrophage functions by onchocystatin, a secreted protein of the filarial nematode Onchocerca volvulus", J IMMUNOL, 167(6), 2001, pp. 3207-3215

Abstract

Immune responses of individuals infected with filarial nematodes are characterized by a marked cellular hyporesponsiveness and a shift of the cytokine balance toward a Th2/Th3 response. This modulation of cellular immune responses is considered as an important mechanism to avoid inflammatory immuneresponses that could eliminate the parasites. We investigated the immunomodulatory potential of a secreted cysteine protease inhibitor (onchocystatin) of the human pathogenic filaria Onchocerca volvulus. Recombinant onchocystatin (rOv17), a biologically active cysteine protease inhibitor that inhibited among others the human cysteine proteases cathepsins L and S, suppressed the polyclonally stimulated and the Ag-driven proliferation of human PBMC. Stimulated as well as unstimulated PBMC in the presence of rOv17 produced significantly more IL-10, which was paralleled in some situations by a decrease of IL-12p40 and preceded by an increase of TNF-a. At the same time, rOv17 reduced the expression of HLA-DR proteins and of the costimulatory molecule CD86 on human monocytes. Neutralization of IL-10 by specific Abs restored the expression of HLA-DR and CD86, whereas the proliferative block remained unaffected. Depletion of monocytes from the PBMC reversed the rOv17-induced cellular hyporeactivity, indicating monocytes to be the target cells of immunomodulation. Therefore, onchocystatin has the potential to contribute to a state of cellular hyporesponsiveness and is a possible pathogenicity factor essential for the persistence of O. volvulus within its human host.

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Documento generato il 04/04/20 alle ore 11:19:35