Original Article
Gene Therapy advance online publication 17 April 2008; doi: 10.1038/gt.2008.59
In vivo transfer of plasmid from food-grade transiting lactococci to murine epithelial cells
J-M Chatel1,2,4, L Pothelune1,2, S Ah-Leung1,2, G Corthier3, J-M Wal1,2 and P Langella3
- 1Commissariat à l'Energie Atomique (CEA), Institut de Biologie et Technologies de Saclay (iBiTecS), Service de Pharmacologie et d'Immunologie, Gif-sur-Yvette, France
- 2Institut National de la Recherche Agronomique (INRA), Unité d'Immuno-Allergie Alimentaire, Domaine de Vilvert, Jouy en Josas cedex, France
- 3Institut National de la Recherche Agronomique (INRA), Unité d'Ecologie et Physiologie du Système Digestif, Domaine de Vilvert, Jouy en Josas cedex, France
Correspondence: Dr J-M Chatel, Institut National de la Recherche Agronomique, Commissariat à l'Energie Atomique, CE Saclay, SPI, Bat 136, Gif sur Yvette 91191, France. E-mail: jean-marc.chatel@jouy.inra.fr
4Current address: INRA-UEPSD, Domaine de Vilvert, 78352 Jouy-en-Josas, France
Received 5 December 2007; Revised 5 February 2008; Accepted 26 February 2008; Published online 17 April 2008.
Abstract
We recently demonstrated that noninvasive food-grade Lactococcus lactis (L. lactis) can deliver eukaryotic expression plasmid in mammalian cells in vitro. Here, we evaluated, in vivo, whether a eukaryotic expression plasmid carried by lactococci can translocate to the epithelial cells of the intestinal membrane. The strain LL(pLIG:BLG1) carrying one plasmid containing a eukaryotic expression cassette encoding
-lactoglobulin (BLG), a major allergen of cow's milk, was orally administered by gavage to mice. BLG cDNA was detected in the epithelial membrane of the small intestine of 40% of the mice and BLG was produced in 53% of the mice. Oral administration of LL(pLIG:BLG1) induced a low and transitory Th1-type immune response counteracting a Th2 response in case of further sensitization. We demonstrated for the first time the transfer of a functional plasmid to the epithelial membrane of the small intestine in mice by noninvasive food-grade lactococci.
Keywords:
lactococcus lactis, beta-lactoglobulin, plasmid transfer
Abbreviations:
LL, Lactococcus lactis MG1363; PBS, phosphate buffer saline; EIA, enzyme immuno assay
