A filarial cysteine protease inhibitor down-regulates T cell proliferation and enhances interleukin-10 production.
Filarial nematodes are a cause of chronic debilitating diseases in the tropics. A hallmark of filariasis is the marked down-regulation and polarization of host immune responses, yet molecular constituents of parasites causing this state have remained undefined. We describe a 17-kDa antigen (Av17) of the rodent filarial parasite Acanthocheilonema viteae, which shows amino acid homologies to cystatin C, a major cysteine protease inhibitor belonging to family 2 of the cystatin superfamily. Av17 is released by filariae in vitro. Exported molecules of A. viteae worms are shown to markedly suppress mitogen-induced T cell proliferation of mice and jirds. Av17 accounts for 45.5% of this suppressive activity in the murine system. Recombinant Av17 (rAv17), expressed in Escherichia coli, exhibits biological activity as a cysteine protease inhibitor and was used to examine the immunomodulatory effects, rAv17 induces down-regulation of murine T cell responses to mitogens, to T cell receptor cross-linking by anti-CD3 antibodies and to specific antigens, and at the same time up-regulation of interleukin-10. Hence, this filarial cystatin is a likely effector molecule of immunomodulation and a potential target for antifilarial intervention.
Hartmann
S
S
Department of Molecular Parasitology, Humboldt University, Berlin, Germany.
Kyewski
B
B
Sonnenburg
B
B
Lucius
R
R
D000818:Animals; D003001:Cloning, Molecular; D015891:Cystatins / Q000494:pharmacology / Q000502:physiology*; D016207:Cytokines / Q000096:biosynthesis; D004153:Dipetalonema / Q000201:enzymology* / Q000276:immunology; D005260:Female; D017238:Genes, Helminth; D015801:Helminth Proteins / Q000276:immunology; D007108:Immune Tolerance; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008213:Lymphocyte Activation / Q000187:drug effects*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology
D015891:Cystatins; D016207:Cytokines; D015801:Helminth Proteins; D007166:Immunosuppressive Agents; D016753:Interleukin-10