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

FRIEDRICH AD; CAMPO V; MANUELLI PN; LEONI J; PAZ ML; GONZÁLEZ MAGLIO DH

Congreso; LXIV Reunión Anual Sociedad Argentina de Inmunología; 2016

In previous reports our lab has proven the anti-tumoral effect of orally administeredlipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG)on anUltraviolet B (UVB)-induced non-melanoma skin cancer mouse model.The aim of the present work was to evaluate underlying mechanisms involved in this anti-tumoral effect. We tested the modulatory capacity of orally administered LTA regarded to gene 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 the transcription of TNF-α, IL-10 and IL-1β in SI and IFN-g in PP was increased at 16hs. At 24 hs we observed a significant increase in TNF-α and IL-12p35 transcription in PP. Finally at 48 hs a significant increase in IFN-g transcription was observed in MLN. In order to evaluate the capacity of orally administered LTA to revert UVB-induced immunosuppression, we performed a hypersensitivity assay to oxazolone after a 12 dose treatment in irradiated and control mice. We observed that UVB-irradiated and LTA-treated mice showed a partial reversion of immunosuppression after oxazolone challenge compared with irradiated and PBS-treated ones.At last, in order to evaluate the anti-tumoral capacity of LTA in an UV-independent model, we tested a multiple doses schedule treatment in animals that already had developed skin tumors but were no longer exposed to UVB irradiation. Animals with visible and multiple skin tumors were administered with LTA by gastric gavage every other day. We demonstrated that LTA is capable to significantly reduce the tumor number and total tumor area after 4 weeks of treatment and that 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 multiple oral administrations. This could be useful to a better understandingof the interactions between molecules isolated from probiotic bacteria and host immune response.