Chlamydia trachomatis infection results in a modest pro-inflammatory cytokine response and a decrease in T cell chemokine secretion in human polarized endocervical epithelial cells

Abstract

The endocervical epithelium is a major reservoir for Chlamydia trachomatis in women, and genital infections are extended in their duration. Epithelial cells act as mucosal sentinels by secreting cytokines and chemokines in response to pathogen challenge and infection. We therefore determined the signature cytokine and chemokine response of primary-like endocervix-derived epithelial cells in response to a common genital serovar (D) of C. trachomatis. For these studies, we used a recently-established polarized, immortalized, endocervical epithelial cell model (polA2EN) that maintains, in vitro, the architectural and functional characteristics of endocervical epithelial cells in vivo including the production of pro-inflammatory cytokines. PolA2EN cells were susceptible to C. trachomatis infection, and chlamydiae in these cells underwent a normal developmental cycle as determined by a one-step growth curve. IL1α protein levels were increased in both apical and basolateral secretions of C. trachomatis infected polA2EN cells, but this response did not occur until 72 hours after infection. Furthermore, protein levels of the pro-inflammatory cytokines and chemokines IL6, TNFα and CXCL8 were not significantly different between C. trachomatis infected polA2EN cells and mock infected cells at any time during the chlamydial developmental cycle up to 120 hours post-infection. Intriguingly, C. trachomatis infection resulted in a significant decrease in the constitutive secretion of T cell chemokines IP10 and RANTES, and this required a productive C. trachomatis infection. Examination of anti-inflammatory cytokines revealed a high constitutive apical secretion of IL1ra from polA2EN cells that was not significantly modulated by C. trachomatis infection. IL-11 was induced by C. trachomatis, although only from the basolateral membrane. These results suggest that C. trachomatis can use evasion strategies to circumvent a robust pro-inflammatory cytokine and chemokine response. These evasion strategies, together with the inherent immune repertoire of endocervical epithelial cells, may aid chlamydiae in establishing, and possibly sustaining, an intracellular niche in microenvironments of the endocervix in vivo.

Polarized Epithelial Cells Secrete Interleukin 6 Apically in the Bovine Endometrium1

“…Polarized human endometrial epithelial cells also secrete more IL6 apically, although IL6 accumulates in the basolateral compartment constitutively and following treatment with LPS [26]. Polarized epithelial cells from other mucosa, including the cervix, intestine, and respiratory tract also principally secrete IL6 apically, but IL6 is also detectable basolaterally [47][48][49]. However, the findings in the present study of an exclusive release of IL6 apically and the absence of detectable IL6 in the basolateral compartment appear unique to bovine endometrial epithelial cells.…”

Morphologic and molecular evaluation of Chlamydia trachomatis growth in human endocervix reveals distinct growth patterns

“…IFNγ was quantified by a cytometric bead array assay (MILLIPLEX MAP Immunology Multiplex Assay). Millipore, Billerica, MA) as previously described (Buckner et al, 2011, 2013). Total indoles were quantified using Salkowski's test (Salkowski, 1885), modified as described by Szkop et al (2012).…”

Transcriptional Profiling of Human Epithelial Cells Infected with Plasmid-Bearing and Plasmid-Deficient Chlamydia trachomatis

“…In fact, Buckner et al (35) reported that infection of human polarized endocervical cells by virulent chlamydiae resulted in only a modest increase in proinflammatory cytokines, leading these investigators to propose that chlamydiae may in fact be stealth pathogens using evasion strategies to circumvent proinflammatory cytokines and T cellactivating chemokines. Considering that natural chlamydial infection of humans is caused predominantly by plasmid-bearing organisms and results in reinfection or persistent infection, an accumulative proinflammatory and immunomodulatory host response might be sufficient to produce an enhanced damaging inflammatory response and a concomitant decreased ability to immunologically control infection in time.…”