ORAL ADMINISTRATION OF LIPOTEICHOIC ACID PROMOTES SKIN INNATE AND ADAPTIVE IMMUNITY WITH ABILITY TO PREVENT UVB-INDUCED IMMUNOTOLERANCE

FRIEDRICH, ADRIAN; TKACHEVA, OLGA; MORELLI, ADRIÁN; SHUFESKY, WILLIAM; LEONI, JULIANA; LARREGINA, ADRIANA; GONZALEZ MAGLIO, DANIEL H

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

The local and systemic effects of microbiome-immune system interaction,relevant for the development of immunotherapies, are just starting to beelucidated. We have previously reported that oral administration of Lactobacillusrhamnosus GG-derived lipoteichoic acid (LTA) reverts the immunosuppressiveeffects caused by UVB skin irradiation. In the present work, we analyzed innateand adaptive immune responses exerted in the cutaneous microenvironment by oralLTA, which prevents the tolerogenic effect of UVB irradiation. To this end, weused the model of delayed type hypersensitivity (DTH) to oxazolone (OXA),applied to C56.BL.6 mice previously treated with eight doses of oral LTA (100μg /dose) followed by UVB irradiation (150 mJ/cm2) for3 days. The innate immunity to OXA was analyzed 48 and 96 hs after sensitizationby characterization of the inflammatory infiltrate in the abdominal skin andthe homing of skin migratory dendritic cells (smiDCs) subsets in local draininglymph nodes (sDLN) by histology and FACS. The skin inflammatory infiltrateinduced by OXA composed by polymorphonuclear cells and macrophages, wassignificantly abrogated by UVB and the diminished inflammatory response wasprevented by oral LTA. Analysis of DC subsets in sDLN demonstrated an increasedactivation and proinflammatory phenotype of all DC subsets as determined by theexpression of CD86, IAb, and Ly6c. Likewise, the number of activated CD44+ Tcells in sDLN after sensitization, and of the effector CD4 and CD8 T cellshoming to the skin following elicitation was significantly higher in micetreated with UVB/OXA/LTA vs. those treated with UVB/OXA. We conclude that theeffect of oral LTA to prevent UVB induced tolerance involves stimulation ofinnate immunity capable of generating inflammatory DCs that activate effectorCD4 and CD8 T cells with skin homing ability.