Abstract
The mucosa of the female reproductive tract plays a pivotal role in host defence. Pregnancy must alter immunological mechanisms at this interface to protect the conceptus. We sought to determine how estradiol (E2) alters the immune-responsiveness of cervical epithelial cells to ligand stimulation of Toll-like receptor (TLR)-2 and -4. Human ectocervical epithelial cells (HECECs) were cultured and co-incubated with two concentrations of E2 and peptidoglycan (PGN) or lipopolysaccharide (LPS) over durations that ranged between 10 minutes and 18 hours. Cytometric Bead Array was performed to quantify eight cytokines in the supernatant fluid. In response to PGN, HECECs co-incubated with E2 released lesser quantities of IL-1ß and IFNγ, higher levels of RANTES, and variable levels of IL-6 and IL-8 than those not exposed to E2. In contrast, HECECs co-incubated with LPS and E2 secreted increased levels of IL-1ß, IL-6, IL-8, and IFNγ at 2 and 18 hours than HECECs not exposed to E2, and reduced levels of RANTES at same study time-points. Estradiol alters the immune-responsiveness of cultured HECECs to TLR2 and TLR4 ligands in a complex fashion that appears to vary with bacterial ligand, TLR subtype, and duration of exposure. Our observations are consistent with the functional complexity that this mucosal interface requires for its immunological roles.
Highlights
The epithelium of the female reproductive tract plays a pivotal role in host defence against pathogens
We have demonstrated that E2 alters the cytokine responses of cultured Human ectocervical epithelial cells (HECECs) when TLR2 and TLR4 signalling pathways are activated
Whilst E2 appears to reduce the release of three of the eight cytokines measured (IL-1β, IL-6, IFNγ) when TLR2 is stimulated by PGN, it enhances the release of the same cytokines as well as IL-8 when the TLR4 receptor is activated by LPS
Summary
The epithelium of the female reproductive tract plays a pivotal role in host defence against pathogens. It secrets specific mucosal proteins such as mucins and defensins [1,2], and recognises pathogen-associated molecular patterns (PAMPs) on microbes [3,4] through pattern recognition receptors (PRR) of the Toll-like receptor (TLR) family amongst others [5,6]. The epithelium provides a mechanical barrier against microbes, and secretes cytokines and antimicrobial peptides which coordinate the local innate and adaptive immune responses [7,8].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
