Oral administration of lipoteichoic acid from Lactobacillus rhamnosus GG overcomes UVB-induced immunosuppression and impairs skin tumor growth in mice

Eur J Immunol. 2019 Nov;49(11):2095-2102. doi: 10.1002/eji.201848024. Epub 2019 Jul 31.

Abstract

There is increasing evidence of the relevant connection and regulation between the gut and skin immune axis. In fact, oral administration of lipoteichoic acid (LTA) from Lactobacillus rhamnosus GG (LGG) prevents the development of UV-induced skin tumors in chronically exposed mice. Here we aim to evaluate whether this LTA is able to revert UV-induced immunosuppression as a mechanism involved in its anti-tumor effect and whether it has an immunotherapeutic effect against cutaneous squamous cell carcinoma. Using a mouse model of contact hypersensitivity, we demonstrate that LTA overcomes UV-induced skin immunosuppression. This effect was in part achieved by modulating the phenotype of lymph node resident dendritic cells (DC) and the homing of skin migratory DC. Importantly, oral LTA reduced significantly the growth of established skin tumors once UV radiation was discontinued, demonstrating that it has a therapeutic, besides the already demonstrated preventive antitumor effect. The data presented here strongly indicates that oral administration of LTA represents a promising immunotherapeutic approach for different conditions in which the skin immune system is compromised.

Keywords: UV radiation; dendritic cells; probiotics; skin diseases; tolerance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology
  • Carcinoma, Squamous Cell / pathology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Cell Movement / radiation effects
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Dendritic Cells / pathology
  • Dendritic Cells / radiation effects
  • Dermatitis, Contact / genetics
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / pathology
  • Female
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / pathology
  • Gastrointestinal Tract / radiation effects
  • Lacticaseibacillus rhamnosus / chemistry*
  • Lipopolysaccharides / isolation & purification
  • Lipopolysaccharides / pharmacology*
  • Lymph Nodes / drug effects
  • Lymph Nodes / immunology
  • Lymph Nodes / pathology
  • Lymph Nodes / radiation effects
  • Mice
  • Mice, Inbred C57BL
  • Skin / drug effects
  • Skin / immunology
  • Skin / pathology
  • Skin / radiation effects
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / genetics
  • Skin Neoplasms / immunology
  • Skin Neoplasms / pathology
  • Teichoic Acids / isolation & purification
  • Teichoic Acids / pharmacology*
  • Ultraviolet Rays / adverse effects*

Substances

  • Antineoplastic Agents
  • Lipopolysaccharides
  • Teichoic Acids
  • lipoteichoic acid