Parasite-specific immunomodulatory functions of filarial cystatin

Schierack, Peter; Lucius, Richard; Sonnenburg, Bettina; Schilling, Klaus; Hartmann, Susanne

doi:10.1128/iai.71.5.2422-2429.2003

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

Parasite-specific immunomodulatory functions of filarial cystatin

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

DOI 10.1128/iai.71.5.2422-2429.2003PMC PMC153229

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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.

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The production of cystatins by some filarial parasites such as Onchocerca volvulus and Acanthocheilonema viteae inhibits cysteine proteases and induces IL-10 production.
“For example, the production of the cystatins by some filarial parasites such as Onchocerca volvulus and Acanthocheilonema viteae leads to the inhibition of the cysteine protease group (i.e., legumains and cathepsin L and S) and induces the production of anti-inflammatory interleukin (i.e., IL-10) [21,22].”
From Emergent and Neglected Equine Filariosis in Egypt: Species Diversity and Host Immune Response (2022) · cites this paper as [21]

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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
Health Sciences › Veterinary › Small Animals › 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

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Parasite-specific immunomodulatory functions of filarial cystatin

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