Chlamydia trachomatis Growth and Cytokine mRNA Response in a Prostate Cancer Cell Line

Abstract

In the present paper, we report that C. trachomatis can be efficiently propagated and affect mRNA expression for two major cytokines, relevant to tumor progression, in CWR-R1 cells, a malignant prostate cell line. CWR-R1 and McCoy cells, a classic cell line for chlamydial research, were grown and infected with C. trachomatis under similar conditions. Cell monolayers were harvested for RNA analysis and immunostaining with major outer membrane protein (MOMP) antibody at 24, 48, and 72 hours of the postinfection (hpi) period. It was shown that the infectious cycle of chlamydial pathogen in CWR-R1 cells resembles the progression of C. trachomatis infection in McCoy cells but with a few important differences. First of all, the initial stage of C. trachomatis propagation in CWR-R1 cells (24 hpi) was characterized by larger inclusion bodies and more intense, specific immunofluorescent staining of infected cells as compared with McCoy cells. Moreover, there was a corresponding increase in infective progeny formation in CWR-R1 cells along with mRNA for EUO, a crucial gene controlling the early phase of the chlamydial development cycle (24 hpi). These changes were more minimal and became statistically insignificant at a later time point in the infectious cycle (48 hpi). Altogether, these data suggest that the early phase of C. trachomatis infection in CWR-R1 cells is accompanied by more efficient propagation of the pathogen as compared with the growth of C. trachomatis in McCoy cells. Furthermore, propagation of C. trachomatis in CWR-R1 cells leads to enhanced transcription of interleukin-6 and fibroblast growth factor-2, genes encoding two important proinflammatory cytokines implicated in the molecular mechanisms of chemoresistance of prostate cancer and its ability to metastasize. The possible roles of reactive oxygen species and impaired mitochondrial oxidation in the prostate cancer cell line are discussed as factors promoting the early stages of C. trachomatis growth in CWR-R1 cells.

In Vitro Modelling of Chlamydia trachomatis Infection in the Etiopathogenesis of Male Infertility and Reactive Arthritis

“…Human prostate epithelial cells showed a similar progression of chlamydial intracellular developmental cycle as that observed in cervical epithelial cells, alongside a comparable infection efficiency (Petyaev et al, 2019). By contrast, in Sertoli and synovial cells, the duration of the different C. trachomatis developmental stages, as well as the number of infectious EBs released from host cells, greatly differed as compared to those observed in cervical epithelial cells, routinely used for chlamydial research (Filardo et al, 2019b).…”

“…Important differences were also observed in the immune and inflammatory host cell responses to C. trachomatis infection, with the activation of different molecular sensors, downstream signalling pathways and inflammatory signatures. Indeed, human prostate cells recognition of C. trachomatis by TLR2/ TLR4 induced a pro-inflammatory state, highlighted by increased levels of IL-1b, IL-6, IL-8 and TNFa (Sellami et al, 2014;Petyaev et al, 2019). By contrast, TLR3-mediated sensing of chlamydial infection in human Sertoli cells did not elicit the activation of the related pathways, namely NFkB and IRF3, as well as the subsequent cytokine production.…”

“…At a later time, a potential link between the inflammatory damage and C. trachomatis infection of the prostate was suggested, since a strong pro-inflammatory response, characterized by NFkB activation and TLR2/TLR4 upregulation, was observed, leading to increased inflammatory cytokine expression, like IL-6, IL-8, IL-1b and tumor necrosis factor (TNF)a (Sellami et al, 2014). Lastly, a recent study has described the efficient propagation of C. trachomatis in a malignant prostate epithelial cell line (CWR-R1) (proportion of infected cells 28.1%) accompanied by enhanced transcription of IL-6 and fibroblast growth factor (FGF)-2 genes, encoding two important pro-inflammatory cytokines involved in the progression of prostate cancer (Petyaev et al, 2019).…”

Prostate Microbiota and Prostate Cancer: A New Trend in Treatment

“…Chlamydia trachomatis is an atypical bacterium that can be transmitted sexually. A recent in vitro study showed that Chlamydia trachomatis can proliferate in prostate cancer cells, resulting in enhanced transcription of IL-6 and FGF-2 genes, while FGF-2 can promote vascularization and metastasis of primary prostate cancer (133). In addition, after Chlamydia trachomatis infection, NF-kappa B was activated, TLR2 and TLR4 were significantly up-regulated, which promoted tumor progression (73).…”

The Role of Microbial Factors in Prostate Cancer Development—An Up-to-Date Review

“…Similarly, Chlamydia trachomatis, cultivated within malignant prostate cells line, was found to affect mRNA expression for two major proinflammatory cytokines- IL-6 and FGF-2. They may both account for the mechanism of chemoresistance of prostate cancer, its vascularization, and, thus, the formation of metastatic lesions [ 46 ]. Just as promising as these results seem, prospective studies, avoiding self-reported assessments, should be held in order to reduce bias and underestimation of exposure.…”