title: Paracellular entry of interleukin-10 producing Lactococcus lactis in inflamed intestinal mucosa in mice.
abstract: BACKGROUND
  Genetically modified Lactococcus lactis secreting interleukin-10 (IL-10) has been demonstrated to provide localized delivery of a therapeutic agent through active in situ synthesis in murine colitis. At present, many aspects of the exact mechanism by which the beneficial effect of the IL-10-producing L. lactis on the mucosa is mediated remain to be clarified.
  
  
  METHODS
  Our aim was to determine the interaction of L. lactis with the intestinal mucosa. Therefore, we administered IL-10-producing L. lactis to healthy mice and in 2 mouse models of chronic colitis. Paraffin sections of ileum and colon samples were examined with confocal and transmission electron microscopy. Ileum and colon homogenates were prepared after flushing and after removal of mucus layer and epithelium. These homogenates and homogenates of mesenteric lymph nodes and spleen were plated on agar and immunoblotting for L. lactis and IL-10 was performed.
  
  
  RESULTS
  Both confocal and electron microscopy showed the presence of lactococci in inflamed intestinal mucosa of mice with colitis. We recovered viable bacteria that could still produce IL-10 from homogenates of inflamed ileum and colon of which mucous and epithelial layers were removed. We did not find lactococci in mesenteric lymph nodes or in the spleen of mice with colitis.
  
  
  CONCLUSIONS
  This study demonstrates uptake of IL-10-secreting L. lactis by the paracellular route in inflamed mucosal tissue. We suggest that IL-10 production by L. lactis residing inside the mucosa in the vicinity of responsive cells can improve the local action of interleukin-10 in inflamed tissue and the efficiency of the treatment.
authors: Department of Pathology, Ghent University, Ghent, Belgium. Anouk.Waeytens@UGent.be
authors: Anouk
authors: A
authors: Waeytens
authors: Liesbeth
authors: L
authors: Ferdinande
authors: Sabine
authors: S
authors: Neirynck
authors: Pieter
authors: P
authors: Rottiers
authors: Martine
authors: M
authors: De Vos
authors: Lothar
authors: L
authors: Steidler
authors: Claude A
authors: CA
authors: Cuvelier
mesh_terms: D000818:Animals; D003092:Colitis / Q000382:microbiology / Q000473:pathology* / Q000628:therapy; D003106:Colon / Q000382:microbiology / Q000473:pathology; D005818:Genetic Engineering; D007082:Ileum / Q000382:microbiology / Q000473:pathology; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000627:therapeutic use; D007413:Intestinal Mucosa / Q000382:microbiology / Q000473:pathology; D013294:Lactococcus lactis / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission
chemical_list: D016753:Interleukin-10