↓ Skip to main content

Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells

Overview of attention for article published in Microbial Cell Factories, August 2016
Altmetric Badge

Citations

dimensions_citation
32 Dimensions

Readers on

mendeley
44 Mendeley
You are seeing a free-to-access but limited selection of the activity Altmetric has collected about this research output. Click here to find out more.
Title
Lactococcus lactis carrying the pValac eukaryotic expression vector coding for IL-4 reduces chemically-induced intestinal inflammation by increasing the levels of IL-10-producing regulatory cells
Published in
Microbial Cell Factories, August 2016
DOI 10.1186/s12934-016-0548-x
Pubmed ID
Authors

Bianca Mendes Souza, Tatiane Melo Preisser, Vanessa Bastos Pereira, Meritxell Zurita-Turk, Camila Prósperi de Castro, Vanessa Pecini da Cunha, Rafael Pires de Oliveira, Ana Cristina Gomes-Santos, Ana Maria Caetano de Faria, Denise Carmona Cara Machado, Jean-Marc Chatel, Vasco Ariston de Carvalho Azevedo, Philippe Langella, Anderson Miyoshi

Abstract

Inflammatory bowel diseases are characterized by chronic intestinal inflammation that leads to severe destruction of the intestinal mucosa. Therefore, the understanding of their aetiology as well as the development of new medicines is an important step for the treatment of such diseases. Consequently, the development of Lactococcus lactis strains capable of delivering a eukaryotic expression vector encoding the interleukin 4 (IL-4) of Mus musculus would represent a new strategy for the elaboration of a more effective alternative therapy against Crohn's disease. The murine IL-4 ORF was cloned into the eukaryotic expression vector pValac::dts. The resulting plasmid-pValac::dts::IL-4-was transfected into CHO cells so that its functionality could be evaluated in vitro. With fluorescent confocal microscopy, flow cytometry and ELISA, it was observed that pValac::dts::IL-4-transfected cells produced IL-4, while non-transfected cells and cells transfected with the empty vector did not. Then, pValac::dts::IL-4 was inserted into L. lactis MG1363 FnBPA(+) in order to evaluate the therapeutic potential of the recombinant strain against TNBS-induced colitis. Intragastric administration of L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) was able to decrease the severity of colitis, with animals showing decreased levels of IL-12, IL-6 and MPO activity; and increased levels of IL-4 and IL-10. Finally, LP-isolated cells from mice administered TNBS were immunophenotyped so that the main IL-4 and IL-10 producers were identified. Mice administered the recombinant strain presented significantly higher percentages of F4/80(+)MHCII(+)Ly6C(-)IL-4(+), F4/80(+)MHCII(+)Ly6C(-)IL-10(+), F4/80(+)MHCII(+)Ly6C(-)CD206(+)CD124(+)IL-10(+) and CD4(+)Foxp3(+)IL10(+) cells compared to the other groups. This study shows that L. lactis MG1363 FnBPA(+) (pValac::dts::IL-4) is a good candidate to maintain the anti-inflammatory and proinflammatory balance in the gastrointestinal tract, increasing the levels of IL-10-secreting regulatory cells and, thus, demonstrating the effectiveness of this novel DNA delivery-based strategy.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 44 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
India 1 2%
Unknown 43 98%

Demographic breakdown

Readers by professional status Count As %
Student > Master 9 20%
Student > Bachelor 7 16%
Student > Ph. D. Student 6 14%
Student > Doctoral Student 3 7%
Unspecified 3 7%
Other 7 16%
Unknown 9 20%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 32%
Immunology and Microbiology 9 20%
Unspecified 3 7%
Agricultural and Biological Sciences 3 7%
Neuroscience 2 5%
Other 2 5%
Unknown 11 25%