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-alpha) from murine macrophages was reduced by recombinant Lactobacillus casei expressing Salmonella OmpC compared to the stimulation of TNF-alpha 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-alpha 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.