Cellular and molecular events involved in the anti-tumoral effect of lipoteichoic acid from Lactobacillus rhamnosus GG

VELARIA CAMPOS; MARIELA PAZ ; PAULA MANUELI; DANIEL GONZALEZ MAGLIO, MARIELA PAZ, ALEJANDRO FERRARI, FEDERICO WEILL, JORGE NIETO AND JULIANA LEONI.; ADRIÁN FRIEDRICH; JULIANA LEONI

BUENOS AIRES

Congreso; SAIC. SAI. SAFE; 2016

Sociedad Argentina de Inmunologia

In previous reports our lab has proven the anti-tumoral effect of orallyadministered lipoteichoic acid (LTA) from Lactobacillusrhamnosus GG (LGG) on an Ultraviolet B (UVB)-induced non-melanoma skincancer mouse model. The aim of the presentwork was to evaluate underlying mechanisms involved in this anti-tumoraleffect. We tested the modulatory capacity of orally administered LTA regarded togene transcription in Peyer´s patches (PP), small intestine free from PP (SI)and mesenteric lymph nodes (MLN) by PCR. After a single dose of 100 μg LTA thetranscription of TNF-α, IL-10 and IL-1β in SI and IFN-g in PP was increased at16hs. At 24 hs we observed a significant increase in TNF-α and IL-12p35transcription in PP. Finally at 48 hs a significant increase in IFN-gtranscription was observed in MLN. In order to evaluate the capacity of orally administered LTA to revertUVB-induced immunosuppression, weperformed a hypersensitivity assay to oxazolone after a 12 dose treatment inirradiated and control mice. We observed that UVB-irradiated and LTA-treatedmice showed a partial reversion of immunosuppression after oxazolone challengecompared with irradiated and PBS-treated ones.At last, in order to evaluate the anti-tumoral capacity of LTA in anUV-independent model, wetested a multiple doses schedule treatment in animals that already haddeveloped skin tumors but were no longer exposed to UVB irradiation. Animalswith visible and multiple skin tumors were administered with LTA by gastricgavage every other day. We demonstrated that LTA is capable to significantlyreduce the tumor number and total tumor area after 4 weeks of treatment andthat this reduction was abolished by the suspension of the treatment. In conclusion, LTA from LGG has proven to produce several in vivo effects after one or multipleoral administrations. This could be useful to a better understanding of theinteractions between molecules isolated from probiotic bacteria and host immuneresponse.