Study of the mechanisms mediated by the oral administration of a probiotic strain against salmonella enterica serovar typhimurium infection tobalb/c mice

CASTILLO, N; PERDIGÓN G; DE MORENO DE LEBLANC, A

San Miguel de Tucuman, Argentina

Simposio; III Simposio Internacional de Bacterias Lácticas. II Encuentro red BAL Argentina; 2009

The prevention of pathogen infections is one of the most extensively studied effects of probiotics. L. casei CRL 431 (Lc) is a probiotic bacterium and its effects on the gut immune cells has been extensively studied. The aim of the present work was to study in a mouse model, the preventive and therapeutic mechanisms induced by L. casei CRL 431 to achieve protection against Salmonella enterica serovar Typhimurium (ST) infection. We determined the period of time for previous and continuous probiotic administration. We analyzed the mechanisms involved in the protection against ST induced by Lc on the first line of intestinal defense such as phagocytic activity of macrophages, Myeloperoxidase (MPO), IgA+ cels, s-IgA and cellular apoptosis. We demonstrated that 7 days (d) Lc administration before infection (7d-ST) decreased the severity of the infection by ST. Continuous administration of Lc for 7 or 10d post infection (PI) (7d-ST-7d Lc or 7d-ST-10d Lc) had the best effect. This continuous administration diminished the mortality compared with infection control group (IC) (0% vs. 30% 7d PI, and 7% vs 70% 10d PI) and also the UFC of ST in the intestine as well as the translocation to other organs. We demonstrated that Lc stimulated cells of the innate immune response. The probiotic administration before pathogen challenge activated the phagocytic activity of macrophages in different sites such as Peyer’s patches (15*±3 vs 8 ±2), spleen (40*±6 vs. 25±8) and peritoneum (64*±4 vs. 38±7) compared with untreated mice. Post infection, the probiotic administration decreased the neutrophils infiltration with the consequent diminution of intestinal inflammation as evidenced by MPO activity values significantly lower for mice that received Lc (0,018 ± 0,009 UE/g and 0,007 ± 0,006 UE/g for 7d-ST and for 7d-ST-Lc, respectively) compared with IC (0,048 ± 0,016 UE/g); and increased the number of IgA+ cells in the lamina propria of the small gut (118 ± 18.7 and 136 ± 19.4 for 7d-ST and 7d-ST-7d Lc, respectively vs. 93 ± 24.1 for IC). This increase was correlated with the release of s-IgA specific against the pathogen in the intestinal fluids (0,23 ± 0.1 and 0,22 ± 0.1 vs. 0,06 ± 0.05 at 7d PI; 0,54 ± 0.1 and 0,68 ± 0.1 vs 0,17 ± 0.1 at 10dPI for 7d-ST and 7d-ST-Lc vs. IC respectively). The mechanism of inhibition of cellular apoptosis was not involved. Although other immune cells and mechanisms could also be implied in the protective effect mediated by Lc against S. Thyphimurium we demonstrated that the probiotic strain assayed, was able to diminish the inflammatory response induced by the pathogen with a diminution of MPO activity, and an increase in both innate and adaptative immune response measured by phagocytic activity of macrophages and specific s-IgA respectively.