Parasite-Specific Immunomodulatory Functions of Filarial Cystatin

Open Access
Publisher Website
Google Scholar
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 nematodesOnchocerca volvulusandAcanthocheilonema viteaewith two homologous proteins of the free-living nematodeCaenorhabditis elegans.Like filarial cystatins, theC. eleganscystatins (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 byC. eleganscystatin was much stronger.C. eleganscystatins lacked a domain involved in inhibition of legumain-like proteases that was present inO. volvuluscystatin. Filarial cystatins suppressed the proliferation of human peripheral blood mononuclear cells (PBMC) and murine spleen cells, while theC. eleganscystatins had this effect to a much lesser extent. Whereas filarial cystatins markedly increased the production of interleukin (IL)-10,C. eleganscystatins increased the production of IL-12 and gamma interferon (IFN-γ) by human PBMC. The cystatins of both the filariae andC. elegansinduced an upregulation of inducible nitric oxide by IFN-γ-stimulated murine macrophages. These data suggest that filarial cystatins but not theC. eleganscystatins downregulate proliferative responses of host cells due to characteristics which might reflect an adaptation of filariae to their parasitic life style.