Well-controlled proinflammatory cytokine responses of Peyer's patch cells to probiotic Lactobacillus casei

P>In order to clarify the probiotic features of immunomodulation, cytokine production by murine spleen and Peyer's patch (PP) cells was examined in response to probiotic and pathogenic bacteria. In spleen cells, probiotic Lactobacillus casei induced interleukin (IL)-12 production by CD11b+ cells more strongly than pathogenic Gram-positive and Gram-negative bacteria and effectively promoted the development of T helper (Th) type 1 cells followed by high levels of secretion of interferon (IFN)-gamma. Although the levels of IL-12 secreted by PP cells in response to L. casei were lower in comparison with spleen cells, Th1 cells developed as a result of this low-level induction of IL-12. However, IFN-gamma secretion by the L. casei-induced Th1 cells stimulated with a specific antigen was down-regulated in PP cells. Development of IL-17-producing Th17 cells was efficiently induced in PP cells by antigen stimulation. Lactobacillus casei slightly, but significantly, inhibited the antigen-induced secretion of IL-17 without a decrease in the proportion of Th17 cells. No bacteria tested induced the development of IL-10-producing, transforming growth factor-beta-producing or Foxp3-expressing regulatory T cells, thus suggesting that certain probiotics might regulate proinflammatory responses through as yet unidentified mechanisms in PP cells. These data show probiotic L. casei to have considerable potential to induce IL-12 production and promote Th1 cell development, but the secretion of proinflammatory cytokines such as IL-12 and IL-17 may be well controlled in PP cells.