ORIGINAL ARTICLE: Quantification and Comparison of Toll-Like Receptor Expression and Responsiveness in Primary and Immortalized Human Female Lower Genital Tract Epithelia

Authors

  • Melissa M. Herbst-Kralovetz,

    1. Departments of Pediatrics and Experimental Pathology, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA;
    2. Center for Infectious Diseases and Vaccinology, Biodesign Institute at Arizona State University, Tempe, AZ, USA;
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  • Alison J. Quayle,

    1. Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA;
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  • Mercedes Ficarra,

    1. Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA;
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  • Sheila Greene,

    1. Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, USA;
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  • William A. Rose II,

    1. Departments of Pediatrics and Experimental Pathology, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA;
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  • Ralph Chesson,

    1. Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, New Orleans, LA, USA
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  • Rae Ann Spagnuolo,

    1. Departments of Pediatrics and Experimental Pathology, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA;
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  • Richard B. Pyles

    1. Departments of Pediatrics and Experimental Pathology, Sealy Center for Vaccine Development, University of Texas Medical Branch, Galveston, TX, USA;
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Richard B. Pyles, Departments of Pediatrics and Experimental Pathology, Sealy Center for Vaccine Development, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555-0436, USA.
E-mail: rbpyles@utmb.edu

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.

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