Cited by 119Parasitic Diseases Research and TreatmentParasites and Host InteractionsHelminth infection and control

The DOI matches its Crossref record; 51 of the 52 references it cites were found in a registry or an index.

Parasite-Specific Immunomodulatory Functions of Filarial Cystatin

Open access

Schierack, Peter, Lucius, Richard, Sonnenburg, Bettina, Schilling, Klaus, Hartmann, Susanne·2003·Infection and Immunity

DOI 10.1128/iai.71.5.2422-2429.2003PMC PMC153229

Open this paper in CoChat — free account

Abstract

Cystatins of parasitic nematodes are well-described pathogenicity factors which contribute to downregulation of T-cell proliferation of their hosts and induce anti-inflammatory cytokine responses. We compared the immunomodulatory effects of two cystatins of the filarial nematodes Onchocerca volvulus and Acanthocheilonema viteae with two homologous proteins of the free-living nematode Caenorhabditis elegans. Like filarial cystatins, the C. elegans cystatins (rCysele1 and rCysele2) possessed domains relevant for inhibition of papain-like proteases and were biologically active inhibitors of human cathepsins B, L, and S. However, the inhibition of cathepsin B by C. elegans cystatin was much stronger. C. elegans cystatins lacked a domain involved in inhibition of legumain-like proteases that was present in O. volvulus cystatin. Filarial cystatins suppressed the proliferation of human peripheral blood mononuclear cells (PBMC) and murine spleen cells, while the C. elegans cystatins had this effect to a much lesser extent. Whereas filarial cystatins markedly increased the production of interleukin (IL)-10, C. elegans cystatins increased the production of IL-12 and gamma interferon (IFN-gamma) by human PBMC. The cystatins of both the filariae and C. elegans induced an upregulation of inducible nitric oxide by IFN-gamma-stimulated murine macrophages. These data suggest that filarial cystatins but not the C. elegans cystatins downregulate proliferative responses of host cells due to characteristics which might reflect an adaptation of filariae to their parasitic life style.

Integrity signals

Registry

Crossref · 10.1128/iai.71.5.2422-2429.2003

Cites

51 of 51 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids
Green, L. C., Wagner, D. A., Glogowski, J. A., Skipper, P. L., Wishnok, J. S., & Tannenbaum, S. R. (1982) · Analytical Biochemistry · doi:10.1016/0003-2697(82)90118-x · Cited by 12,061
Interleukin 10 (IL-10) and viral IL-10 strongly reduce antigen-specific human T cell proliferation by diminishing the antigen-presenting capacity of monocytes via downregulation of class II major histocompatibility complex expression.
Malefyt, R. D. W., Haanen, J. B. A. G., Spits, H., Roncarolo, M., Velde, A. A. T., Figdor, C. G., Johnson, K., KASTELEIN, R. A., Yssel, H., & de Vries, J. E. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.4.915 · Cited by 1,930
Induction by Antigen of Intrathymic Apoptosis of CD4 + CD8 + TCR lo Thymocytes in Vivo
MURPHY, K. M. M., Heimberger, A. B., & Loh, D. Y. (1990) · Science · doi:10.1126/science.2125367 · Cited by 1,714
[41] Cathepsin B, cathepsin H, and cathepsin L
Barrett, A. J., & Kirschke, H. (1981) · Methods in Enzymology · doi:10.1016/s0076-6879(81)80043-2 · Cited by 1,698
2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans
Wilson, R. K., Ainscough, R., Anderson, K., Baynes, C., Berks, M., Bonfield, J., Burton, J., Connell, M. A. O., Copsey, T., Cooper, J., et al. (1994) · Nature · doi:10.1038/368032a0 · Cited by 1,459
Induction of Direct Antimicrobial Activity Through Mammalian Toll-Like Receptors
Thoma-Uszynski, S., Stenger, S., Takeuchi, O., Ochoa, M. T., Engele, M., Sieling, P. A., Barnes, P. F., Röllinghoff, M., Bölcskei, P., Wagner, M., et al. (2001) · Science · doi:10.1126/science.291.5508.1544 · Cited by 729
Cathepsin L: Critical Role in Ii Degradation and CD4 T Cell Selection in the Thymus
Nakagawa, T. Y., Roth, W., Wong, P., Nelson, A., Farr, A. G., Deussing, J. M., Villadangos, J. A., Ploegh, H. L., Peters, C., & Rudensky, A. Y. (1998) · Science · doi:10.1126/science.280.5362.450 · Cited by 675
Essential Role for Cathepsin S in MHC Class II–Associated Invariant Chain Processing and Peptide Loading
Riese, R. J., Wolf, P. R., Brömme, D., Natkin, L. W., Villadangos, J. A., Ploegh, H. L., & Chapman, H. A. (1996) · Immunity · doi:10.1016/s1074-7613(00)80249-6 · Cited by 536
Immunological modulation and evasion by helminth parasites in human populations
Maizels, R. M., Bundy, D. A. P., Selkirk, M. E., Smith, D. F., & Anderson, R. M. (1993) · Nature · doi:10.1038/365797a0 · Cited by 529
Properties and Functions of Interleukin-10
Mosman, T. R. (1994) · Advances in immunology · doi:10.1016/s0065-2776(08)60449-6 · Cited by 495
Impaired Invariant Chain Degradation and Antigen Presentation and Diminished Collagen-Induced Arthritis in Cathepsin S Null Mice
Nakagawa, T. Y., Brissette, W. H., Lira, P. D., Griffiths, R., Petrushova, N., Stock, J. L., McNeish, J. D., Eastman, S., Howard, E. D., Clarke, S. R. M., et al. (1999) · Immunity · doi:10.1016/s1074-7613(00)80021-7 · Cited by 418
An asparaginyl endopeptidase processes a microbial antigen for class II MHC presentation
Manoury, B., Hewitt, E. W., MORRICE, N. A., Dando, P. M., Barrett, A. J., & Watts, C. K. W. (1998) · Nature · doi:10.1038/25379 · Cited by 365
Antigen-specific cellular hyporesponsiveness in a chronic human helminth infection is mediated by Th3/Tr1-type cytokines IL-10 and transforming growth factor-β but not by a Th1 to Th2 shift
Doetze, A., Satoguina, J., Burchard, G., Rau, T., Löliger, C., Fleischer, B., & Hoerauf, A. (2000) · International Immunology · doi:10.1093/intimm/12.5.623 · Cited by 357
Up-regulation of monocytic IL-10 by tumor necrosis factor-α and cAMP elevating drugs
Platzer, C., Meisel, C., Vogt, K., Platzer, M., & Volk, H. (1995) · International Immunology · doi:10.1093/intimm/7.4.517 · Cited by 317
Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation
Deussing, J. M., Roth, W., Säftig, P., Peters, C., Ploegh, H. L., & Villadangos, J. A. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.8.4516 · Cited by 266
Regulatory T cells and inflammatory bowel disease
Groux, H., & Powrie, F. M. (1999) · Immunology Today · doi:10.1016/s0167-5699(99)01510-8 · Cited by 257
Filarial Nematode Parasites Secrete a Homologue of the Human Cytokine Macrophage Migration Inhibitory Factor
Pastrana, D., Raghavan, N., Fitzgerald, P., Eisinger, S. W., Metz, C., Bucala, R., Schleimer, R., Bickel, C., & Scott, A. L. (1998) · Infection and Immunity · doi:10.1128/iai.66.12.5955-5963.1998 · Cited by 253
Inhibition of mammalian legumain by some cystatins is due to a novel second reactive site.
Alvarez-Fernandez, M., Barrett, A. J., Gerhartz, B., Dando, P. M., Ni, J., & Abrahamson, M. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.27.19195 · Cited by 238
Bm-CPI-2, a cystatin homolog secreted by the filarial parasite Brugia malayi, inhibits class II MHC-restricted antigen processing
Manoury, B., Gregory, W. F., Maizels, R. M., & Watts, C. (2001) · Current Biology · doi:10.1016/s0960-9822(01)00118-x · Cited by 223
The role of lysosomal proteinases in MHC class Il‐mediated antigen processing and presentation
Nakagawa, T. Y., & Rudensky, A. Y. (1999) · Immunological Reviews · doi:10.1111/j.1600-065x.1999.tb01361.x · Cited by 182
The reproductive lifespan of Onchocerca volvulus in West African savanna
Plaisier, A. P., van Oortmarssen, G. J., Remme, J. H. F., & Habbema, J. D. F. (1991) · Acta Tropica · doi:10.1016/0001-706x(91)90015-c · Cited by 174
TGF-β1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression
Heath, V. L., Murphy, E. E., Crain, C., Tomlinson, M. G., & O’Garra, A. (2000) · European Journal of Immunology · doi:10.1002/1521-4141(200009)30:9 · Cited by 172
High Levels of Spontaneous and Parasite Antigen-Driven Interieukin-10 Production Are Associated with Antigen-Specific Hyporesponsiveness in Human Lymphatic Filariasis
Mahanty, S., Mollis, S. N., Ravichandran, M., Abrams, J. S., Kumaraswami, V., Jayaraman, K., Ottesen, E. A., & Nutman, T. B. (1996) · Journal of Infectious Diseases · doi:10.1093/infdis/173.3.769 · Cited by 165
Immunomodulatory properties of cystatins
Vray, B., Hartmann, S., & Hoebeke, J. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8525-4 · Cited by 161
Modulation of Human T Cell Responses and Macrophage Functions by Onchocystatin, a Secreted Protein of the Filarial Nematode Onchocerca volvulus
Schönemeyer, A., Lucius, R., Sonnenburg, B., Brattig, N., Sabat, R., Schilling, K., Bradley, J., & Hartmann, S. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.167.6.3207 · Cited by 155
A filarial cysteine protease inhibitor down‐regulates T cell proliferation and enhances interleukin‐10 production
Hartmann, S., Kyewski, B., Sonnenburg, B., & Lucius, R. (1997) · European Journal of Immunology · doi:10.1002/eji.1830270920 · Cited by 141
Structural Basis for the Biological Specificity of Cystatin C
Hall, A., Håkansson, K., Mason, R. W., GRUBB, A. O., & Abrahamson, M. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.10.5115 · Cited by 128
Nippocystatin, a Cysteine Protease Inhibitor from Nippostrongylus brasiliensis, Inhibits Antigen Processing and Modulates Antigen-Specific Immune Response
Dainichi, T., Maekawa, Y., Ishii, K., Zhang, T., Nashed, B. F., Sakai, T., Takashima, M., & Himeno, K. (2001) · Infection and Immunity · doi:10.1128/iai.69.12.7380-7386.2001 · Cited by 125
Successful Therapy of Lethal Murine Visceral Leishmaniasis with Cystatin Involves Up-Regulation of Nitric Oxide and a Favorable T Cell Response
Das, L., Datta, N., Bandyopadhyay, S. K., & Das, P. K. (2001) · The Journal of Immunology · doi:10.4049/jimmunol.166.6.4020 · Cited by 123
A Novel Serpin Expressed by Blood-Borne Microfilariae of the Parasitic Nematode Brugia malayi Inhibits Human Neutrophil Serine Proteinases
Zang, X., Yazdanbakhsh, M., Jiang, H., Kanost, M. R., & Maizels, R. M. (1999) · Blood · doi:10.1182/blood.v94.4.1418 · Cited by 121
Profound suppression of cellular proliferation mediated by the secretions of nematodes
Allen, J. E., & MacDonald, A. S. (1998) · Parasite Immunology · doi:10.1046/j.1365-3024.1998.00151.x · Cited by 116
Cystatins Up-regulate Nitric Oxide Release from Interferon-γ- activated Mouse Peritoneal Macrophages
Verdot, L., Lalmanach, G., Vercruysse, V., Hartmann, S., Lucius, R., Hoebeke, J., Gauthier, F., & Vray, B. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.45.28077 · Cited by 107
Differential regulation of monocytic tumor necrosis factor‐α and interleukin‐10 expression
Meisel, C., Vogt, K., Platzer, C., Randow, F., Liebenthal, C., & Volk, H. (1996) · European Journal of Immunology · doi:10.1002/eji.1830260726 · Cited by 100
A Novel Member of the Transforming Growth Factor-β (TGF-β) Superfamily from the Filarial NematodesBrugia malayiandB. pahangi
Gomez‐Escobar, N., Lewis, E., & Maizels, R. M. (1998) · Experimental Parasitology · doi:10.1006/expr.1998.4248 · Cited by 93
Switch of CD4+ T Cell Differentiation from Th2 to Th1 by Treatment with Cathepsin B Inhibitor in Experimental Leishmaniasis
Maekawa, Y., Himeno, K., Ishikawa, H. T., Hisaeda, H., Sakai, T., Dainichi, T., Asao, T., Good, R. A., & Katunuma, N. (1998) · The Journal of Immunology · doi:10.4049/jimmunol.161.5.2120 · Cited by 92
Importance of the evolutionarily conserved glycine residue in the N-terminal region of human cystatin C (Gly-11) for cysteine endopeptidase inhibition
Hall, A., Dalbøge, H., GRUBB, A. O., & Abrahamson, M. (1993) · Biochemical Journal · doi:10.1042/bj2910123 · Cited by 83
Immunomodulatory properties of a phosphorylcholine‐containing secreted filarial glycoprotein
Harnett, W., Deehan, M. R., Houston, K. M., & Harnett, M. M. (1999) · Parasite Immunology · doi:10.1046/j.1365-3024.1999.00267.x · Cited by 83
Chicken cystatin stimulates nitric oxide release from interferon‐γ‐activated mouse peritoneal macrophages via cytokine synthesis
Verdot, L., Lalmanach, G., Vercruysse, V., Hoebeke, J., Gauthier, F., & Vray, B. (1999) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.1999.00964.x · Cited by 81
Interleukin-10 and Antigen-Presenting Cells Actively Suppress Th1 Cells in BALB/c Mice Infected with the Filarial Parasite Brugia pahangi
Osborne, J., & Devaney, E. (1999) · Infection and Immunity · doi:10.1128/iai.67.4.1599-1605.1999 · Cited by 77
Litomosoides sigmodontis cystatin acts as an immunomodulator during experimental filariasis
Pfaff, A. W., Schulz-Key, H., Soboslay, P. T., Taylor, D. W., MacLennan, K., & Hoffmann, W. H. (2002) · International Journal for Parasitology · doi:10.1016/s0020-7519(01)00350-2 · Cited by 65
Cystatins of filarial nematodes up‐regulate the nitric oxide production of interferon‐γ‐activated murine macrophages
Hartmann, S., Schönemeyer, A., Sonnenburg, B., Vray, B., & Lucius, R. (2002) · Parasite Immunology · doi:10.1046/j.1365-3024.2002.00459.x · Cited by 55
Probing the functional role of the N-terminal region of cystatins by equilibrium and kinetic studies of the binding of Gly-11 variants of recombinant human cystatin C to target proteinases
Björk, I., Brieditis, I., & Abrahamson, M. (1995) · Biochemical Journal · doi:10.1042/bj3060513 · Cited by 47
Molecular cloning of an immunodominant antigen of Onchocerca volvulus.
Lucius, R., Erondu, N., Kern, A., & Donelson, J. E. (1988) · The Journal of Experimental Medicine · doi:10.1084/jem.168.3.1199 · Cited by 45
Improving the in vitro antigen specific T cell proliferation assay: the use of interferon-alpha to elicit antigen specific stimulation and decrease bystander proliferation
von Baehr, V., Mayer, W., Liebenthal, C., von Baehr, R., Bieger, W. P., & Volk, H. (2001) · Journal of Immunological Methods · doi:10.1016/s0022-1759(01)00297-6 · Cited by 40
Expression of NGF-like polypeptides and immunoreactivity related to the two types of neurotrophin receptors in earthworm tissues.
Davoli, C., Marconi, A., Serafino, A., Iannoni, C., Marcheggiano, A., & Ravagnan, G. (2002) · ARCA (Università Ca' Foscari Venezia) · Cited by 37
Immunosuppressive proteins secreted by the gastrointestinal nematode parasite Heligmosomoides polygyrus
PRITCHARD, D. I., Lawrence, C. E., Appleby, P. A., Gibb, I. A., & Glover, K. A. (1994) · International Journal for Parasitology · doi:10.1016/0020-7519(94)90140-6 · Cited by 32
Genetic variants of bovine beta-lactoglobulin. A novel wild-type beta-lactoglobulin W and its primary sequence.
Leung-Tack, J., Tavéra, C., Er-Raki, A., Gensac, M. C., & Collé, A. (1990) · PubMed · Cited by 30
Protein degradation in MHC class II antigen presentation: opportunities for immunomodulation
Medd, P. G., & Chain, B. (2000) · Seminars in Cell and Developmental Biology · doi:10.1006/scdb.2000.0162 · Cited by 27
Genetic Variants of Bovine β-Lactoglobulin. A Novel Wild-type β-Lactoglobulin W and its Primary Sequence
Godovac‐Zimmermann, J., Krause, I., Buchberger, J., WEISS, G., & Klostermeyer, H. (1990) · Biological Chemistry Hoppe-Seyler · doi:10.1515/bchm3.1990.371.1.255 · Cited by 22
Selective increased presentation of type II collagen by leupeptin
Manoury, B. (1997) · International Immunology · doi:10.1093/intimm/9.4.581 · Cited by 20
Immunoregulation in Onchocerciasis: Persons with Ocular Inflammatory Disease Produce a Th2-like Response to Onchocerca volvulus Antigen
Plier, D. A., Awadzi, K., & Freedman, D. O. (1996) · The Journal of Infectious Diseases · doi:10.1093/infdis/174.2.380 · Cited by 17

Sorted by citations

Genomic Insights into the Origin of Parasitism in the Emerging Plant Pathogen Bursaphelenchus xylophilus
Kikuchi, T., Cotton, J. A., Dalzell, J. J., Hasegawa, K., Kanzaki, N., McVeigh, P., Takanashi, T., Tsai, I. J., Assefa, S., Cock, P., et al. (2011) · PLoS Pathogens · doi:10.1371/journal.ppat.1002219 · Cited by 434
PROTEASES IN PARASITIC DISEASES
McKerrow, J. H., Caffrey, C. R., Kelly, B. L., Loke, P., & Sajid, M. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.1.110304.100151 · Cited by 429
Genome Sequence of a Polydnavirus: Insights into Symbiotic Virus Evolution
Espagne, E., Dupuy, C., Huguet, E., Cattolico, L., Provost, B., Martins, N., Poirié, M., Périquet, G., & Drezen, J. (2004) · Science · doi:10.1126/science.1103066 · Cited by 265
Immune defence, parasite evasion strategies and their relevance for ‘macroscopic phenomena’ such as virulence
Schmid‐Hempel, P. (2008) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2008.0157 · Cited by 251
A Helminth Immunomodulator Reduces Allergic and Inflammatory Responses by Induction of IL-10-Producing Macrophages
Schnoeller, C., Rausch, S., Pillai, S., Avagyan, A., Wittig, B. M., Loddenkemper, C., Hamann, A., Hamelmann, E. H., Lucius, R., & Hartmann, S. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.6.4265 · Cited by 240

See all 119

Authors: Schierack, P., Lucius, R., Sonnenburg, B., Schilling, K., & Hartmann, S.
Affiliations: Humboldt-Universität zu Berlin (DE)
Friedrich Schiller University Jena (DE)
ORCID: Schierack, Peter
Lucius, Richard
Schilling, Klaus
Hartmann, Susanne
Venue: Infection and Immunity
Publisher: American Society for Microbiology
Published: 2003-05
Volume: 71
Issue: 5
Pages: 2422-2429
ISSN: 0019-9567 (ISSN-L)
1098-5522
DOI: 10.1128/iai.71.5.2422-2429.2003
PMC: PMC153229
OpenAlex: W2157772863
Cited by: 119
References: 52
Citations by year: 2025: 1 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 7 · 2020: 4 · 2019: 4 · 2018: 2 · 2017: 9 · 2016: 4 · 2015: 3 · 2014: 5 · 2013: 8 · 2012: 4
FWCI: 5.67
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
Locations: Infection and Immunity (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Deutsche Forschungsgemeinschaft
Topics: Health Sciences › Medicine › Infectious Diseases › Parasitic Diseases Research and Treatment
Life Sciences › Immunology and Microbiology › Parasitology › Parasites and Host Interactions
Life Sciences › Immunology and Microbiology › Parasitology › Helminth infection and control
Keywords: Onchocerca volvulus, Acanthocheilonema viteae, immunomodulation, T cell proliferation, cathepsin inhibition, IL-10, IL-12, interferon-gamma, inducible nitric oxide, macrophages, virulence factors, parasitic nematodes
MeSH terms: Amino Acid Sequence, Animals, Filarioidea, Interferon-gamma, Lymphocyte Activation, Mice, Inbred BALB C, Molecular Sequence Data, Recombinant Proteins, Cystatins, Cytokines, Caenorhabditis elegans, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Parasite-Specific Immunomodulatory Functions of Filarial Cystatin

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks