SUMMARYBacteroides fragilis toxin (BFT) has been shown to be capable of inducing intestinal mucosal inflammation in animals. Such inflammation may be responsible for diarrhoea, which occurs in some, but not all human carriers of enterotoxigenic strains of B. fragilis (ETBF). We have studied responses to BFT by different human intestinal epithelial cell lines and subsequently investigated the expression of IL-8 and TGF-b by T84 cells. The latter were selected because their responses to BFT, characterized by morphological changes and cell death by apoptosis, were similar to those we have recently observed in primary human colonocytes. We show that BFT dose-dependently increased the expression of transcripts and protein of the polymorphonuclear cell chemoattractant IL-8. BFT also dose-dependently induced the release of TGF-b , which has been shown to enhance the repair of the injured intestinal epithelium. However, the secreted TGF-b was almost exclusively in the biologically inactive form, as determined by Mv1Lu bioassay. Our studies therefore suggest that exposure of colonic epithelial cells in vivo to high concentrations of BFT can initiate an inflammatory response via secreted IL-8. BFT-induced release of latent TGF-b may facilitate the subsequent repair of the injured epithelium, following its activation by proteases from neighbouring cells. Variation in cytokine responses by colonic epithelial cells in vivo could be an important determinant in the development of mucosal disease and symptoms in response to ETBF.
An attempt was undertaken to determine whether a concurrent infection of Trichinella spiralis and T. pseudospiralis can reduce cellular in®ltrations against the former species during the muscle phase of worm development. BALB/c, nude and CBA/N mice were orally infected with either species or a mixture of both. New-born larvae (NBL) of either or both species were also injected subcutaneously into the right/left leg of BALB/c mice. In T. spiralis oral infection, myositis was strongest in BALB/c, intermediate in CBA/N and weakest in nude mice. In T. pseudospiralis oral infection, slight cellular in®ltrations were observed around the worms in BALB/c but not in nude or CBA/N mice. However, in mixed oral infections of two species, in®l-trations around the sites of T. spiralis were not reduced. In mice injected with T. pseudospiralis NBL, in®ltrations around the infective-stage larvae were mostly absent. However, in mice injected with T. spiralis NBL, prominent granulomatous reactions were observed near the sites of worms. The tissue reaction was substantially stronger than that in oral infections. In mice injected with NBL of both species (into dierent legs), a heavy in®ltration was also observed at the site of T. spiralis. A marked increase in levels of IL-4 and IL-6 was detected in the popliteal lymphocytes of BALB/c mice injected with either live or dead NBL of T. spiralis at days 15 and 20 post-injection. This indicated that the worms mainly elicited a T H 2 response during the muscle phase of development. An indirect¯uorescent antibody test and laser confocal microscopic studies demonstrated the presence of CD4 and CD8 cells in the cytoplasmic region of the nurse cell complex of T. spiralis.
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