Quantification and comparison of toll-like receptor expression and responsiveness in primary and immortalized human female lower genital tract epithelia

Am J Reprod Immunol. 2008 Mar;59(3):212-24. doi: 10.1111/j.1600-0897.2007.00566.x. Epub 2008 Jan 12.

Abstract

Problem: To better understand innate immune responses to sexually-transmitted infection (STI) and the appropriateness of epithelial cell (EC) models of the vaginal and cervical mucosa, quantified toll-like receptor (TLR) expression from a population of women is needed.

Method of study: TLR gene expression was quantified in primary and immortalized endocervical, ectocervical, and vaginal EC from multiple donors. TLR bioactivity was evaluated by cytokine elaboration.

Results: TLR1-3 and 5-9 were expressed in each EC type with TLR2, 3, 5, 6 and CD14 expressed most abundantly. TLR4 was expressed by endocervical and vaginal EC. Agonist stimulation of TLR2, 3, 5 and 6 elicited cytokines. TLR4 and 7-9 were minimally expressed and were not consistently bioactive. Immortalized EC generally modeled primary cultures but elaborated significantly reduced cytokine levels.

Conclusion: TLR expression patterns were remarkably conserved across the study population and evaluated tissues indicating a predictable responsiveness to STI. The results support cautious use of immortalized cells for genital tract modeling.

Publication types

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

MeSH terms

  • Adult
  • Cervix Uteri / cytology
  • Cervix Uteri / immunology
  • Cervix Uteri / metabolism*
  • Chemokine CCL2 / immunology
  • Chemokine CCL2 / metabolism
  • Cyclopropanes
  • Diglycerides / immunology
  • Epithelium / immunology
  • Epithelium / metabolism
  • Female
  • Flagellin
  • Gene Expression Profiling
  • Guanosine / analogs & derivatives
  • Humans
  • Immunity, Innate*
  • Immunity, Mucosal
  • Interleukin-1beta / immunology
  • Interleukin-1beta / metabolism
  • Interleukin-6 / immunology
  • Interleukin-6 / metabolism
  • Interleukin-8 / immunology
  • Interleukin-8 / metabolism
  • Lipopolysaccharides
  • Oligopeptides / immunology
  • RNA, Double-Stranded
  • Sexually Transmitted Diseases / immunology
  • Toll-Like Receptors / biosynthesis*
  • Toll-Like Receptors / immunology
  • Vagina / cytology
  • Vagina / immunology
  • Vagina / metabolism*

Substances

  • Chemokine CCL2
  • Cyclopropanes
  • Diglycerides
  • FSL-1 lipoprotein, synthetic
  • Interleukin-1beta
  • Interleukin-6
  • Interleukin-8
  • Lipopolysaccharides
  • N2-cyclopropylamine-guanosine
  • Oligopeptides
  • RNA, Double-Stranded
  • Toll-Like Receptors
  • Guanosine
  • Flagellin