Toll-like receptor 4 mediates the response of epithelial and stromal cells to lipopolysaccharide in the endometrium.
BACKGROUND
Ascending infections of the female genital tract with bacteria causes pelvic inflammatory disease (PID), preterm labour and infertility. Lipopolysaccharide (LPS) is the main component of the cell wall of Gram-negative bacteria. Innate immunity relies on the detection of LPS by Toll-like receptor 4 (TLR4) on host cells. Binding of LPS to TLR4 on immune cells stimulates secretion of pro-inflammatory cytokines such as IL-6, chemokines such as CXCL1 and CCL20, and prostaglandin E(2). The present study tested the hypothesis that TLR4 on endometrial epithelial and stromal cells is essential for the innate immune response to LPS in the female genital tract.


RESULTS
Wild type (WT) mice expressed TLR4 in the endometrium. Intrauterine infusion of purified LPS caused pelvic inflammatory disease, with accumulation of granulocytes throughout the endometrium of WT but not Tlr4(-/-) mice. Intra-peritoneal infusion of LPS did not cause PID in WT or Tlr4(-/-) mice, indicating the importance of TLR4 in the endometrium for the detection of LPS in the female genital tract. Stromal and epithelial cells isolated from the endometrium of WT but not Tlr4(-/-) mice, secreted IL-6, CXCL1, CCL20 and prostaglandin E(2) in response to LPS, in a concentration and time dependent manner. Co-culture of combinations of stromal and epithelial cells from WT and Tlr4(-/-) mice provided little evidence of stromal-epithelial interactions in the response to LPS.


CONCLUSIONS
The innate immune response to LPS in the female genital tract is dependent on TLR4 on the epithelial and stromal cells of the endometrium.
Sheldon
Iain Martin
IM
Institute of Life Science, School of Medicine, Swansea University, Singleton Park, Swansea, United Kingdom. I.M.Sheldon@swansea.ac.uk
Roberts
Mark H
MH
D000818:Animals; D016207:Cytokines / Q000276:immunology; D004717:Endometrium / Q000276:immunology*; D004847:Epithelial Cells / Q000276:immunology*; D005260:Female; D018836:Inflammation Mediators / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017154:Stromal Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4