Lactococcus lactis carrying the pValac DNA expression vector coding for IL-10 reduces inflammation in a murine model of experimental colitis

ZURITA-TURK, M.; DEL CARMEN, S.; GOMES SANTOS, C.A.; BASTOS PEREIRA, V.; CARA, D.C.; LECLERCQ, S.; DE MORENO DE LEBLANC, A.; AZEVEDO, V.; CHATEL, J.M.; LEBLANC, J.G.; MIYOSHI, A.

BMC BIOTECHNOLOGY

BIOMED CENTRAL LTD

Lugar: Londres; Año: 2014 vol. 14 p. 1 - 11

1472-6750

Inflammatory bowel disease (IBD), such as Crohn´s Disease (CD) and Ulcerative Colitis (UC), are intestinal disorders characterized by inflammation in the gastrointestinal tract (GIT). Despite much research in the last years, the exact etiology and pathogenesis of these disorders remain unclear; hence, there is presently no cure  and current treatments include the use of anti-inflammatory drugs and corticosteroidsthat that often lead to many undesired side-effects and poor clinical results. Interleukin-10 (IL-10) is one of the most important anti-inflammatory cytokines involved in the intestinal immune system and its absence has been shown to be involved in IBD . Despite its great potential, oral treatment with IL-10 has not been very sucessful due to its extreme sensitivity and therefore survival in the GIT, and systemic treatments have caused many undesirable side effects; therefore, novel approaches for the use IL-10 for IBD therapy are under study. We previously presented the development of an invasive strain of Lactococcus lactis (L. lactis) producing Fibronectin Binding Protein A (FnBPA) from Staphylococcus aureus (S. aureus). This strain was capable of delivering, directly to host cells, a eukaryotic DNA expression vector coding for IL-10 of Mus musculus (pValac:IL-10), and diminish inflammation in a trinitrobenzene sulfonate (TNBS)-induced mouse model. As a new strategy for the prevention and/or treatment of IBD, the aim of this work was to evaluate the therapeutic effect of two L. lactis strains carrying the therapeutic pValac:IL-10 plasmid in the prevention of colitis in a DSS-induced mouse model. Diseased mice that received either one of the L. lactis strains containing the pValac:IL-10 plasmid showed lower inflammation scores in their large intestines (both at macroscopic and microscopic level), resembled healthy animals, higher secreted IgA from intestinal lavages and IL-10 and lower TNF-α, IL-6 and IL-17 levels. No microbial translocation to the liver of L. lactis MG1363 FnBPA was observed, indicating that this strain could be proposed for  human clinical trials.