Probiotic lipoteichoic acid (LTA) modulates UV-induced immunosuppression and anti-SCC immune response

FRIEDRICH, ADRIAN D; LEONI, JULIANA; CELA, ELIANA M; GONZALEZ MAGLIO, DANIEL H; CAMPO, VALERIA E; PAZ, MARIELA L

Pisa

Congreso; 17th Congress of the European Society for Photobiology; 2017

European Society for Photobiology

Ultraviolet radiation (UVr) promotesvery well-known alterations on immune system, decreasing specific T cellresponses among other effects. This deficient T cell response allow tumor skincells to establish and grow, generating a tumor. Probiotics have been employedsince ancient times, to positively modulate immune responses, not only in thegastrointestinal tract but also in cutaneous tissue. As an example, probioticshave been successfully employed in the treatment of atopic dermatitis.In our laboratory, we have demonstratedthat lipoteichoic acid (LTA) isolated from Lactobacillusrhamnosus GG is able to reduce the multiplicity and to delay the onset ofSquamous Cell Carcinomas (SCC) in chronically UV-exposed mice, whenadministered orally all along the chronic irradiation schedule. In the presentwork, we aim to understand the mechanisms that may explain the observedanti-tumoral effect of orally administered LTA.In first place, we analysed theactivation of gut-associated lymphoid tissue immune cells, in control andLTA-treated mice. We observed increments in the transcription of IL1β and IL-10 12h after treatment in the gut, TNF-α and IL-12p3524h after treatment in Peyer?s patches (PP) and IFN-γ 48h after treatment in mesentericlymph nodes (MLN). Moreover, an increase in the percentage of activateddendritic cells was observed in MLN. Secondly, we studied the oral LTA capacityto modulate UV-induced immunosuppression. We performed 8 administrations of LTAor PBS each other day to C57/BL6 mice, prior to 3 exposures to 150 mJ/cm2of UVr. Twenty-four hours later, we sensitised animals with oxazolone,including a non-irradiated group used as control. Mice were challenged in theear 6 days later, to observe the T cells-triggered inflammation. UVrsignificantly decreased inflammation, while LTA-treatment restored normalinflammatory response (p<0.05). Finally, we decided to evaluate theanti-tumoral effect once irradiation was suspended and tumors were already established.To this purpose, we chronically irradiated mice with 50 mJ/cm2thrice a week during 5 months, until all animals showed at least one SCCstablished. Then irradiation was suspended and animals were separated in twogroups, one LTA-treated and one control. LTA promotes a better control ofUV-induced SCC after 4 weeks of treatment, by decreasing the number of tumorsper animal (p<0.05) and the total tumor area (p<0.01).Wecan conclude that oral LTA activates mucosal immune system, restoring specificimmune responses after UV irradiation and leading to a stronger immune responseonce tumors are established.