Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease

Abstract

Apoptosis of active T lymphocytes constitutes a major control mechanism of immune homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn's disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor alpha (P < 0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local microecology may restore immune homeostasis.

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

“…Among them, a number of cytokine genes were upregulated by PMA/IO, which suggested T cell proliferation (IL-2, IFN-c and IL-17A) (Murphy et al 2007) and T cell activation (IL2RA) (Gao et al 2010;Ledger et al 2004). The reduction in the expression of those genes after treatment with the lactobacilli suggests that all three strains probably counteract the molecular events leading to T cell activation, as shown before for the probiotic strain L. casei DN 114-001 (Carol et al 2006). Reduction of IFN-c could be a very interesting probiotic feature since, besides its crucial role for innate and adaptive immunity against intracellular pathogens, prolonged high levels of IFN-c lead to chronic autoimmune and inflammatory diseases, such as multiple sclerosis and IBD (Bouma and Strober 2003;Rovedatti et al 2009;Schoenborn and Wilson 2007).…”

Probiotics and immunity

“…Decreased levels of Bifi dobacterium and Lactobacillus strains have been described in fecal samples, whereas raised counts of Enterococcus and Bacteroides species are found in infl amed mucosa of patients with IBD. High levels of infl ammatory cytokines (TNF-α and IL-1β) and IL-8 are produced by infl amed colonic mucosa of both UC and CD patients, [65][66][67][68][69] while the role of autoantibodies remains to be determined. 70 In addition, lamina propria T cells from IBD patients secrete elevated levels of IL-6, and IL-6/STAT-3 signaling is upregulated.…”

“…[67][68][69] Downregulation of IL-6, which can exhibit antiapoptotic activity, may play a role in this process. 69 Indeed, in a mouse model of chronic colitis, treatment with neutralizing IL-6 receptor antibodies prevented macroscopic signs of infl ammation in the colon while markedly increasing the number of lamina propria CD4+ T cells undergoing apoptosis. 99 Probiotics in animal models of colitis There are numerous animal models of colitis.…”

Probiotics in Surgery

“…on the other hand, they can induce apoptosis of the lymphocytes programmed to kill the host's own microflora. This particular mechanism was observed among patients suffering from nonspecific bowel inflammation receiving probiotics (13). Rigby et al (14) described the stimulating effect of probiotic bacteria on the production of antiinflammatory cytokines (IL10), with the simultaneous increase of pro-inflammatory cytokines (IL2) caused by pathogenic bacteria.…”