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Lactococcus lactis as a delivery system of macrophage Migration Inhibitory Factor (MIF) to enhance mucosal transport of biologically active compounds


In order to induce a robust and effective immune response at mucosal level, bacteria, viruses and other antigens must cross the intestinal barrier. Highly specialised antigen-sampling M cells are strategically located in certain areas of the gut and play a fundamental role in the induction of mucosal and systemic immune responses by transporting antigens to the mucosal-associated immune system (MALT). Large numbers of in vivo studies, in which the follicle-associated epithelium (FAE) of gut-associated lymphoid tissue (GALT) or, more recently, nasal-associated lymphoid tissue (NALT) was challenged with pathogens or microparticles clearly demonstrated that M cells within the FAE are the primary site for antigen-sampling.
We have recently found that the cytokine Macrophage Migration Inhibitory factor (MIF) plays an important role in the formation of fully operational M cells in the FAE and here we commend the idea of investigating the potential of MIF as novel enhancer of M cell-mediated transport of antigens an d therapeutics to the mucosal immune system. The main objective of this proposal is to use the recombinant lactic acid bacterium L. lactis for the delivery of MIF to the mucosal (oral and nasal) immune system in order to increase the number of fully operat ional M cells of the FAE.
In this way we will be able to design novel and more effective strategy for oral or nasal delivery of vaccines and other biologically active compounds. Generation of LAB expressing lymphokines has already been demonstrated and the advantage of using L. lactis is that it has GRAS status and is routinely used in food fermentation and as probiotic functional food ingredient.

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