Distinct immunomodulatory properties of Lactobacillus paracasei strains.

AIMS: This study was performed to ascertain the immunomodulatory effect of Lactobacillus paracasei strains. These strains were also genetically characterized. METHODS AND RESULTS: The strains were genetically differentiated by using the fluorescent-amplified fragment length polymorphism technique, which led to the identification of several molecular markers unique to each strain. To determine the immunomodulatory properties, we evaluated the effect of strains on dendritic cell maturation, dextran uptake, ability to induce proliferation of allogenic T cells and cytokine secretion. The results indicated that all the strains stimulated phenotypic maturation of dendritic cells (DCs), but they acted differently on DCs in relation to the other tested properties; notably, a different effect on cytokine secretion was detected. CONCLUSIONS: The results of this study revealed different immunomodulatory properties of strains of the species Lact. paracasei. Strain IMPC 4.1 showed an interesting anti-inflammatory ability. Probiotic strains IMPC 2.1 and LMG P-17806 were characterized by a similar and intermediate ability to induce cytokine secretion in contrast to the very low ability of strain LMG 23554. SIGNIFICANCE AND IMPACT OF STUDY: Our results confirm that each single strain of a bacterial species appears to influence the immune system in a peculiar manner. The evaluation of the different types and/or levels of cytokines whose secretion is induced by each strain could be relevant to define its pro- or anti-inflammatory properties and its more appropriate clinical use.

Immunomodulatory effects of Lactobacillus casei administration in a mouse model of gliadin-sensitive enteropathy.

Coeliac disease (CD) is a very common food-sensitive enteropathy, which is triggered by gluten ingestion and is mediated by CD4(+) T cells. In addition, alterations in the intestinal microbiota that is normally involved in the homeostasis of GALT (gut-associated lymphoid tissue) seem to play a role in CD. In accordance with these findings, we previously reported that Lactobacillus casei can induce a strong enhancement of the T cell-mediated response to gliadin without inducing enteropathy. In this study, we analysed the effects of L. casei administration in a mouse model of gliadin-induced villous damage that was recently developed and involves the inhibition of cyclo-oxygenase (COX) activities in gliadin-sensitized HLA-DQ8 transgenic mice. To address the issue, we assessed the weight loss, the intestinal cytokine pattern, the density of CD25(+) cells and morphometry of the gut mucosa. We confirmed that COX inhibition in sensitized mice caused villus blunting, dysregulated expression of tumour necrosis factor (TNF)-α and reduced gliadin-specific IL-2 production. Notably, the administration of probiotic strain induced a complete recovery of villus blunting. This finding was associated with a delay in weight decrease and a recovery of basal TNF-α levels, whereas the numbers of CD25(+) cells and the levels of IL-2 remained unchanged. In conclusion, our data suggest that the administration of L. casei can be effective in rescuing the normal mucosal architecture and GALT homeostasis in a mouse model of gliadin-induced enteropathy.

Trichothecenes NIV and DON modulate the maturation of murine dendritic cells.

Nivalenol (NIV) and Deoxynivalenol (DON), mycotoxins of the trichothecene family are considered very common food contaminants. In this work, we investigated whether the immunotoxic effects ascribed to these trichothecenes may be mediated by perturbations in the activity of dendritic cells (DCs). Murine bone marrow-derived DCs were used to evaluate the effects of NIV and DON on the LPS-induced maturation process. We found that the expression of the class II MHC and of the accessory CD11c molecules, but not of the costimulatory CD86 marker, was down-regulated by NIV and DON exposure in LPS-treated DCs, as well as nitric oxide (NO) production. Interestingly, NIV, but not DON, induced DC necrosis. Moreover, the analysis of the cytokine pattern showed that IL-12 and IL-10 expressions induced by LPS exposure were suppressed by both trichothecenes in a dose-dependent fashion. On the other hand, the secretion of the proinflammatory cytokine TNF-alpha was increased as a direct consequence of DON and NIV exposure. Taken together, our data indicated that the immunotoxicity of NIV and DON was related to the capacity of both trichothecenes to interfere with phenotypic and functional features of maturing DCs.

Small intestinal enteropathy in non-obese diabetic mice fed a diet containing wheat.

AIMS/HYPOTHESIS: A deranged mucosal immune response and dietary factors may play an important role in the pathogenesis of type 1 diabetes. The aims of our work were to look for the presence of small intestinal enteropathy in non-obese diabetic (NOD) mice in relation to the presence of wheat proteins in the diet, and to assess their role in the risk of developing diabetes. METHODS: Female NOD mice were fed a standard or gluten-free diet or a gluten-free diet with the addition of wheat proteins (MGFD). Small intestine architecture, intraepithelial CD3(+) infiltration, epithelial expression of H2-IA, mRNA for IFN-gamma and IL-4 were assessed. RESULTS: NOD mice fed a standard diet showed reduced villous height, increased intraepithelial infiltration by CD3(+) cells and enhanced expression of H2-IA and IFN-gamma mRNA when compared with mice on the gluten-free diet. The cumulative diabetes incidence at 43 weeks of age was 65% in the latter and 97% in the former (p<0.01). Mice on MGFD also showed increased epithelial infiltration and a higher incidence of diabetes. CONCLUSIONS/INTERPRETATION: Mice fed a wheat-containing diet showed a higher incidence of diabetes, signs of small intestinal enteropathy and higher mucosal levels of proinflammatory cytokines.