EVASION OF THE ENDOCERVICAL EPITHELIAL PRO-INFLAMMATORY CYTOKINE RESPONSE BY Chlamydia trachomatis
Document Type
Presentation
Start Date
22-10-2010 3:00 PM
End Date
22-10-2010 4:30 PM
Description
The endocervical epithelium is the primary site of infection for the intracellular bacteria, Chlamydia trachomatis. Without treatment, infections can last for months to years, and a small proportion of women develop chronic disease leading to pelvic inflammatory disease and infertility. One hypothesis posed by researchers in the field is that the pathology associated with chlamydia! disease is mediated by pro-inflammatory cytokines/chemokines initiated and sustained by epithelial cells. We recently established a polarized endocervical epithelial cell model (A2EN) that maintains functional characteristics of endocervical epithelial cells in vivo, including the production of pro-inflammatory cytokines/chemokines upon TLR stimulation. We have now utilized this model in order to test our hypothesis. First, we established that polarized A2EN cells are susceptible to C. trachomatis serovar D (UW3) infection, and chlamydiae in these cells undergo a normal developmental cycle as determined by one step growth curves. Infection of polarized A2EN cells, however, failed to result in a significant up-regulation of many proinflammatory cytokines/ chemokines, such as IL6 and CXCLS; this finding was also confirmed in primary endocervical epithelial cells. C. trachomatis infection also abrogated the MIP1 ~. RANTES, and IP10 response in polarized A2EN cells exposed to poly l:C, a potent TLR 3 agonist, suggesting that the bacteria are actively suppressing this innate epithelial response. Moreover, C. trachomatis infected polarized A2EN cell secretions were unable to stimulate uninfected cells, and even abrogated IL6, TNFa, and IL 1a secretion. We, therefore, examined secretion of the anti-inflammatory cytokines, TGF~ and IL11, and found that both were upregulated in response to C. trachomatis infection in polarized A2EN cells. The suppression of pro-inflammatory cytokine/chemokine secretion, and production of anti-inflammatory cytokines together suggest that 1) chlamydiae actively evade the pro-inflammatory innate epithelial cell immune response, 2) epithelial cells may not initiate and sustain the pro-inflammatory response to C. trachomatis, thus allowing for a long term association of the bacteria with the host in vivo, and 3) pathology associated with chlamydia! disease may be mediated by an alternative mechanism.
Recommended Citation
Buckner, Lyndsey; Green, Sheila; and Quayle, Alison J., "EVASION OF THE ENDOCERVICAL EPITHELIAL PRO-INFLAMMATORY CYTOKINE RESPONSE BY Chlamydia trachomatis" (2010). Dr. Joseph M. Moerschbaecher, III Graduate Research Day. 4.
https://digitalscholar.lsuhsc.edu/grad_rs/2010/poster2/4
EVASION OF THE ENDOCERVICAL EPITHELIAL PRO-INFLAMMATORY CYTOKINE RESPONSE BY Chlamydia trachomatis
The endocervical epithelium is the primary site of infection for the intracellular bacteria, Chlamydia trachomatis. Without treatment, infections can last for months to years, and a small proportion of women develop chronic disease leading to pelvic inflammatory disease and infertility. One hypothesis posed by researchers in the field is that the pathology associated with chlamydia! disease is mediated by pro-inflammatory cytokines/chemokines initiated and sustained by epithelial cells. We recently established a polarized endocervical epithelial cell model (A2EN) that maintains functional characteristics of endocervical epithelial cells in vivo, including the production of pro-inflammatory cytokines/chemokines upon TLR stimulation. We have now utilized this model in order to test our hypothesis. First, we established that polarized A2EN cells are susceptible to C. trachomatis serovar D (UW3) infection, and chlamydiae in these cells undergo a normal developmental cycle as determined by one step growth curves. Infection of polarized A2EN cells, however, failed to result in a significant up-regulation of many proinflammatory cytokines/ chemokines, such as IL6 and CXCLS; this finding was also confirmed in primary endocervical epithelial cells. C. trachomatis infection also abrogated the MIP1 ~. RANTES, and IP10 response in polarized A2EN cells exposed to poly l:C, a potent TLR 3 agonist, suggesting that the bacteria are actively suppressing this innate epithelial response. Moreover, C. trachomatis infected polarized A2EN cell secretions were unable to stimulate uninfected cells, and even abrogated IL6, TNFa, and IL 1a secretion. We, therefore, examined secretion of the anti-inflammatory cytokines, TGF~ and IL11, and found that both were upregulated in response to C. trachomatis infection in polarized A2EN cells. The suppression of pro-inflammatory cytokine/chemokine secretion, and production of anti-inflammatory cytokines together suggest that 1) chlamydiae actively evade the pro-inflammatory innate epithelial cell immune response, 2) epithelial cells may not initiate and sustain the pro-inflammatory response to C. trachomatis, thus allowing for a long term association of the bacteria with the host in vivo, and 3) pathology associated with chlamydia! disease may be mediated by an alternative mechanism.
Comments
See abstract book page 48