Impairment of dendritic cell function by excretory-secretory products: A potential mechanism for nematode-induced immunosuppression
✍ Scribed by Mariela Segura; Zhong Su; Ciriaco Piccirillo; Mary M. Stevenson
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- English
- Weight
- 689 KB
- Volume
- 37
- Category
- Article
- ISSN
- 0014-2980
No coin nor oath required. For personal study only.
✦ Synopsis
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.