Up-Regulation of Fas (CD95) and Induction of Apoptosis in Intestinal Epithelial Cells by Nematode - Derived Molecules

Abstract

Infection by the intestinal nematode Nippostrongylus brasiliensis induces acceleration of apoptosis in the small intestinal villus epithelial cells in vivo. In the present study, we examined whether worm extract or excretory-secretory product induces apoptosis in the rat intestinal epithelial cell line IEC-6 in vitro. In the presence of worm extract or excretory-secretory product (>6 g/ml), IEC-6 cell growth was significantly suppressed, and there was a concomitant increase in the number of detached cells in culture dishes. Detached cells showed nuclear fragmentation, activation of caspase-3, and specific cleavage of poly(ADP-ribose) polymerase, suggesting that apoptosis was induced in these cells. Semiquantitative reverse transcription-PCR showed that expression of Fas (CD95) mRNA was up-regulated as early as 6 h after addition of excretorysecretory product, while Fas ligand expression and p53 expression were not up-regulated. Fluorescenceactivated cell sorter analyses revealed a significant increase in Fas expression and a slight increase in FasL expression in IEC-6 cells cultured in the presence of excretory-secretory product, while control IEC-6 cells expressed neither Fas or FasL. These results indicated that N. brasiliensis worms produce and secrete biologically active molecules that trigger apoptosis in intestinal epithelial cells together with up-regulation of Fas expression, although the mechanism of induction of apoptosis remains to be elucidated.

Reaction of the mussel Mytilus galloprovincialis (Bivalvia) to Eugymnanthea inquilina (Cnidaria) and Urastoma cyprinae (Turbellaria) concurrent infestation

“…Whilst protozoan parasites inhibit host cell apoptosis attempting to perpetuate their life cycle within cells (Heussler et al, 2001;Lüder et al, 2001) it seems that extracellulary-living helminths modulate host apoptosis by its induction in target host immune cells. This has been proposed recently for intestinal nematodes, filariae, schistosomes and cestode Taenia crassiceps (Chen et al, 2002;Jenson et al, 2002;Kuroda et al, 2002;Lopez-Briones et al, 2003) and our data show that similar mechanism develops in turbellaria-bivalve system. Caspase positive reaction inferred by IHC in M. galloprovincialis was triggered in cases of turbellarian infestation, in contrast with hydroids, suggesting more complex host-parasite interaction and persistent attempts of the parasite to survive bivalve reaction.…”

Study of the distribution of active caspase‐3‐positive cells in turbot, Scophthalmus maximus (L.), enteromyxosis

“…The stages of development may release substances that induce apoptosis in infected areas, similarly to that which occurs in rat intestinal epithelial cells infected with nematode‐derived molecules (Kuroda et al . ) or in human intestinal epithelial cells infected with Giardia intestinalis (Kofoid & Christiansen, 1915; Panaro et al . ).…”

“…Strikingly, during infection with E. scophthalmi, the active caspase-3-positive cells were located in the parasitized folds but were not necessarily in direct contact with the myxosporean. The stages of development may release substances that induce apoptosis in infected areas, similarly to that which occurs in rat intestinal epithelial cells infected with nematode-derived molecules (Kuroda et al 2002) or in human intestinal epithelial cells infected with Giardia intestinalis (Kofoid & Christiansen, 1915;Panaro et al 2007). Another reason would be an increase in the rate of epithelial cell turnover promoted by cytokines as a strategy to expel the parasites, as reported during infection with Trichuris trichuria in human (Cliffe et al 2005).…”

Caspase-3-Mediated Apoptosis of Human Eosinophils by the Tissue-Invading Helminth <i>Paragonimus westermani</i>

“…For example, secretory products released from schistosomulae of S. mansoni [35], adults of Nippostrongylus brasiliensis [36]and hookworm [37]dose-dependently induced apoptosis of immune cells. In addition, it has been shown that persistent cellular immunosuppression with a concomitant increasing load of parasites in vivo was closely related to enhanced apoptosis of T cells after in vitro stimulation of the parasite antigen [38].…”