Role of the TLR pathway in the modulation of the immune system activation mediated by Lactobacillus casei CRL 431

MALDONADO GALDEANO, CAROLINA; PERDIGÓN, GABRIELA; THIEBLEMONT, NATHALIE

Palmas de Mallorca

Workshop; 6th International Immunonutrition Workshop; 2012

Sociedad Internacional de Inmunonutrición

The intestine is a complex environment where it coexists a dynamic community of microorganisms called microbiota. The microorganisms reside in the intestine in harmony with the host cells (1) and the establishments of these microorganisms are essential for the development of the immune system. The local effects of the microbiota on gut homeostasis (2) and gut immune development have been delineated (3, 4); however, studies have addressed the systemic effect of the microbiota (5) as a result of the translocation of it from the gut lumen into the circulation, but the mechanisms involved are still poorly understood (6). Studies performed in the laboratory using conventional BALB/C mice showed that the administration of the probiotic bacterium: Lactobacillus casei (L. casei) CRL431 not only exerted activation of the innate immunity in the gut but also had effect in the systemic immunity response with enhanced of the phagocytic activity of peritoneal macrophages. Previous studies demonstrated that the TLR, principally the TLR2, are involved in the intestinal signals initiated when probiotic bacteria were administrated to conventional mice in the drinking water (7). In the present work we investigated the capacity of a probiotic bacterium to modulate the macrophage activation using TLR2-, TLR4- or the MyD88- deficient mice involved in the innate immunity. We also evaluated the systemic immune response by measured the IgG anti-Ovalbumin. Mice were given with the probiotic bacterium L. casei CRL 431 in the drinking water during 7 consecutive days or with a commercial probiotic fermented milk (5 days). After that, by ex vivo assays we evaluated the phagocytic activity of peritoneal macrophages. Other groups of animal previously administered with the probiotic bacterium or with the PFM were sensitized with three subcutaneously injections of 1% ovalbumin, the blood samples were obtained 10 days after the last injection. Ex vivo results showed that TLR2, TLR4 and the adaptor molecules MYD88 were involved in the phagocytic process of probiotics and the phagocytosis and the probiotic administration could not improve the macrophages phagocytic activity. In vitro results obtained from IL-10 production by macrophages following probiotics treatment since only MyD88 is required in the production of this cytokine. The results showed that the levels of anti-Ovalbumin IgG were dependent of the TLR2 or TLR4 or MyD88 expression being dispensable for this activation. These results suggest even when the signal through TLRs are critical in the innate immune response and that L. casei induces immune system activation through TLRs, this signaling pathway is not the only one involved in this observed immune system activation.