Immunomodulatory and protective effect of probiotic Lactobacillus casei against Candida albicans infection in malnourished mice

VILLENA JULIO; HARO CECILIA; SALVA SUSANA; AGÜERO GRACIELA; ALVAREZ SUSANA

Tucumán

Simposio; III International Symposium on Lactic Acid Bacteria. II Argentinean LAB Net Meeting; 2009

Centre de Referencia para lactobacilos (CERELA-CCT-CONICET)

Lactobacillus casei CRL 431 (Lc), administered as a supplement in a repletion diet, is able to improve the resistance of malnourished mice to the systemic challenge with Candida albicans (Ca). The aim of this work was to study the immunological mechanisms involved in the protective effect achieved by the repletion treatment supplemented with the probiotic bacteria. Weaned mice were malnourished after consuming a protein-free diet (PFD) for 21 days. Malnourished mice were fed a balanced conventional diet (BD) for 7 days or BD for 7 days with supplemental L. casei (109 cells/mouse/day) on days 6 and 7 (BD+Lc). The malnourished control group (MC) received PFD while the well-nourished control (WC) mice consumed BD. At the end of treatments the different groups of mice were infected intraperitoneally with Ca (107 cells/mouse). The number and activity of neutrophils and macrophages and the levels of TNF-á, IFN-g, IL-6, IL-10 and IL-17 were studied in peritoneal cavity, blood, liver and spleens. Studies were performed before the challenge with Ca (day 0) and on days 1, 3 and 5 post-infection (dpi). The microbicidal and phagocytic activity of peritoneal macrophages and the activation and recruitment of neutrophils to the infected organs in the MC group was significantly lower than those of WC mice. Repletion with BD improved these parameters but without reaching the values of WC group. Animals treated with BD+Lc showed numbers and activities of phagocytes similar to the WC group. (Liver myeloperoxidase activity: WC=15.7±2.1 U/mg; MC=5.2±1.1; BD=7.6±1.3; BD+Lc=16.3±1.5; peritoneal NBT+ cells: WC=42.8±1.2 U/mg; MC=23.4±3.7; BD=31.7±3.4; BD+Lc=43.6±1.7). TNF-á, INF-ã and IL-6 increased in all experimental groups, but the MC mice showed significantly lower levels than the WC group. Mice replete with BD and BD+Lc showed significantly higher levels of these cytokines than the MC group, but only BD+Lc mice presented values similar to the WC group (Blood TNF-á: WC=420.3±5.9 pg/mL; MC=106.9±3.1; BD=307.9±1.7; BD+Lc=435.8±2.8). Malnutrition also impaired the production of IL-17 in response to infection and both repletion treatments normalized the levels of these cytokine. Levels of IL-10 in the MC group were significantly lower than in WC mice. BD mice showed levels of IL-10 significantly higher than those of the MC group, without reaching the values of the WC mice. On the contrary, IL-10 in the BD+Lc group was significantly higher than in WC mice (Blood IL-10: WC=235.9±2.3 pg/mL; MC=101.5±1.8; BD=193.9±1.7; BD+Lc=317.5±2.2). The results show that the addition of a L. casei to the repletion diet accelerates the normalization of the innate immune response against C. albicans, which is characterized by an efficient recruitment and activation of phagocytes, as well as an efficient release of pro-inflammatory cytokines. In addition, treatment with the probiotic bacteria induces an increase in IL-10 levels, which would help to prevent the damage caused by the inflammatory response.