Reduction of Tumor Necrosis Factor Alpha-Inducing Capacity of Recombinant Lactobacillus casei via Expression of Salmonella OmpC

The insertion of a heterologous gene into commensal bacteria is a common technique to develop a delivery agent for vaccination and therapies, but the pleiotropic effects of genetic modifications need to be investigated before its use in practical applications. Although supplemental properties provid...

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Bibliographic Details
Published in:Applied and Environmental Microbiology 2009-05, Vol.75 (9), p.2727-2734
Main Authors: Kajikawa, A, Igimi, S
Format: Article
Language:English
Subjects:
Animals
Antigens
Bacteria
Biological and medical sciences
Cell Line
Cell Wall - immunology
Cell walls
Cells, Cultured
Effects
Fundamental and applied biological sciences. Psychology
Gene expression
Genetics
Genetics and Molecular Biology
Lactobacillus casei
Lactobacillus casei - genetics
Lactobacillus casei - immunology
Macrophages - immunology
Macrophages - microbiology
Mice
Microbiology
Porins - genetics
Porins - immunology
Recombinant Proteins - genetics
Recombinant Proteins - immunology
Salmonella
Studies
Tumor Necrosis Factor-alpha - biosynthesis
Tumor Necrosis Factor-alpha - immunology
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Summary:The insertion of a heterologous gene into commensal bacteria is a common technique to develop a delivery agent for vaccination and therapies, but the pleiotropic effects of genetic modifications need to be investigated before its use in practical applications. Although supplemental properties provided by the expression of heterologous antigens have been reported, the negative or side effects on the immune-modulating properties caused by recombination are barely understood. In the present study, we fortuitously found that the secretion of tumor necrosis factor alpha (TNF-α) from murine macrophages was reduced by recombinant Lactobacillus casei expressing Salmonella OmpC compared to the stimulation of TNF-α secretion by nonexpressing L. casei. This reduction could not be attributed to OmpC as a purified protein. The main component of the OmpC-expressing strain included in the attenuation of TNF-α release seemed to be the cell wall, which exhibited higher sensitivity against N-acetylmuramidase than that of nonexpressing strains. These results suggest that the recombinant strain expressing a specific heterologous antigen might be digested rapidly in macrophages and lose immune-stimulating capability at an early time point.
ISSN:0099-2240
1098-5336
1098-6596
DOI:10.1128/AEM.01916-08