Sustained Interleukin‐6 and Interleukin‐8 Expression Following Infection with Chlamydia trachomatis Serovar L2 in a HeLa/THP‐1 Cell Co‐culture Model

Abstract

Correspondence to: Dr M. Ravaoarinoro, Département de microbiologie médicale et infectiologie, section de microbiologie clinique, CHUM-Hôtel-Dieu, 3840 rue St-Urbain, Porte 5-206, Montréal, QC H2W 1T8, Canada. E-mail: madeleine.ravaoarinoro.chum@ssss.gouv.qc.ca AbstractChlamydia trachomatis, an intracellular obligate bacterium, remains responsible for a large spectrum of disorders that can progress to chronic diseases, resulting in severe sequelae, such as tubal infertility and blindness. These sequelae may be due to deleterious immune responses induced by repeated or persistent infections. By initiating and regulating inflammation as well as immune responses, pro-inflammatory cytokines secreted by local infected epithelial and immune cells, such as monocytes, may play an essential role in immunity and in the immunopathogenesis of chlamydial diseases. In this study, we mimicked the in vivo interaction between epithelial cells and monocytes by co-culturing epithelial-like HeLa cells with monocyte-like THP-1 cells. Pro-inflammatory cytokines [interleukin-b (IL-1b), IL-6, IL-8, IL-10, IL-12p70 and tumour necrosis factora (TNF-a)] were measured by multiplexed cytometric bead array assay over a period of 18 days. We observed that pro-inflammatory cytokine secretion was augmented after C. trachomatis infection in HeLa and THP-1 cells. However, this heightened secretion was subsequently reduced. When infected HeLa cells were co-cultured with THP-1 cells, IL-6 and IL-8 secretion was sustained, IL-1b expression followed a bell-shaped curve and IL-10, IL-12p70 and TNF-a synthesis was downregulated. IL-6 and IL-8 may be involved in the immunopathogenesis of chronic chlamydial infections. We also observed that throughout C. trachomatis persistence induced by doxycycline (Dox) treatment, IL-1b, IL-6, IL-8 and TNF-a expression was reduced, whereas the synthesis of IL-10 and IL12p70 remained unchanged but not sustained. Thus, during chlamydial persistence infection evoked by treatment with Dox, none of the tested cytokines showed sustained expression.

Effects of low-dose doxycycline on cytokine secretion in human monocytes stimulated with Aggregatibacter actinomycetemcomitans

“…Chlamydia trachomatis infection of monocytic THP-1 cells, it has been shown that the production of these four pro-inflammatory cytokines is reduced in response to LDD (43).Taken together, it can be deduced that LDD has general anti-inflammatory properties. Inhibition of bacteria-induced cytokine secretion by doxycycline occurred in a dose-dependent manner, within a concentration range between 5-25 µg/ml, which did not show any evidence of cytotoxicity.…”

Toll-Like Receptor 2 Recognition of the MicrosporidiaEncephalitozoonspp. Induces Nuclear Translocation of NF-κB and Subsequent Inflammatory Responses

“…5). Similarly, Mpiga et al showed that IL-8 expression was sustained but that TNF-␣ levels peaked and decreased in cultures infected with Chlamydia trachomatis (27). Control of IL-8 expression has been shown to be regulated by several signaling pathways and transcriptional regulators, including but not limited to NF-B.…”

Human and Pathogen Factors Associated with Chlamydia trachomatis-Related Infertility in Women

“…Similarly, mRNA measurement of cytokine expression after C. trachomatis infection of HeLa cells, SiHa cervix squamous carcinoma cells, and HT-29 colon adenocarcinoma cells showed increased levels of IL-8, GRO␣, granulocytemacrophage CSF, IL-6, and IL-1␣ (59). A HeLa-THP-1 coculture model attempting to recapitulate the in vivo cellular cross talk also identified IL-6 and IL-8 cytokine secretion that was sustained during C. trachomatis infection with IL-1␤ transiently detected (71). IL-6 and IL-8 were also detected by using cervical and epithelial cell infection models (59).…”