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

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 TLRI-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.