Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppression

Authors

  • Mariela Segura,

    1. Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada
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  • Zhong Su,

    1. Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada
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  • Ciriaco Piccirillo,

    1. Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada
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  • Mary M. Stevenson Dr.

    Corresponding author
    1. Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, McGill University, Montreal, Canada
    • Centre for the Study of Host Resistance, Research Institute of the McGill University Health Centre, Montreal General Hospital, Room L11-409, 1650 Cedar Avenue, Montreal, Quebec, Canada H3G 1A4, Fax: 1-514-934-8332
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Abstract

To determine whether helminth-derived products modulate dendritic cell (DC) function, we investigated the effects of excretory-secretory products (ES) and adult worm homogenate (AWH) derived from the gastrointestinal nematode Heligmosomoides polygyrus (Hp) on murine bone marrow-derived DC (BMDC). Compared to the TLR9 ligand CpG, Hp-derived products alone failed to induce DC activation. ES, but not AWH, inhibited BMDC cytokine and chemokine production and co-stimulatory molecule expression (CD40, CD86 and MHC class II) induced by TLR ligation. TLR ligand-independent, PMA-induced DC activation was unaffected by ES. Recipients of ES-treated BMDC pulsed with OVA had suppressed Ab responses in vivo, irrespective of the Th1 or Th2 isotype affiliation, compared to recipients of control OVA-pulsed BMDC. Importantly, suppression occurred even in the presence of the potent type 1 adjuvant CpG. In contrast to untreated OVA-pulsed BMDC, ES-treated BMDC pulsed with OVA had reduced co-stimulatory molecule and cytokine expression. CD4+CD25+Foxp3 T cells, which secreted high IL-10 levels, were generated in co-cultures of OT-II OVA-specific TCR-transgenic CD4+ T cells and ES-treated BMDC. These IL-10-secreting T cells suppressed effector CD4+ T cell proliferation and IFN-γ production, the latter effect mediated by an IL-10-dependent mechanism. Together, these results demonstrate that nematode ES impaired DC function and suppressed both Th1 and Th2 adaptive immune responses possibly by inducing regulatory T cells.

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