Levels of different cytokines in women and men with asymptomatic genital infection caused by Chlamydia

Bua, Alessandra; Cannas, Sara; Zanetti, Stefania Anna Lucia; Molicotti, Paola

doi:10.3855/jidc.9810

Cited by 4 publications

(5 citation statements)

References 18 publications

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“…These results are similar to those observed by Buckner et al ( 2011 ), where perceptible levels of IL-6, IL-8, IP10, and RANTES were detected. In addition, we observed that the cytokine response of the model in the presence or absence of a chlamydial infection was comparable to that previously observed in this and other human and mouse cell lines (Buckner et al 2013 , Hwang et al 2015 , Bua et al 2019 , Yang et al 2019 ). These results indicate that the A2EN cervical epithelium 3D model could serve as a suitable platform for studies of chlamydial infection.…”

Section: Resultssupporting

confidence: 88%

Three-dimensional models of the cervicovaginal epithelia to study host–microbiome interactions and sexually transmitted infections

Edwards

McComb

Gleghorn

et al. 2022

Pathogens and Disease

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Two-dimensional (2D) cell culture systems have historically provided controlled, reproducible means to analyze host-pathogen interactions observed in the human reproductive tract. Although inexpensive, straightforward, and requiring a very short time commitment, these models recapitulate neither the functionality of multi-layered cell types nor the associated microbiome that occurs in a human. Animal models have commonly been used to recreate the complexity of human infections. However, extensive modifications of animal models are required to recreate interactions that resemble those in the human reproductive tract. Three-dimensional (3D) cell culture models have emerged as alternative means of reproducing vital elements of human infections at a fraction of the cost of animal models and on a scale that allows for replicative experiments. Here we describe a new 3D model that utilizes transwells with epithelial cells seeded apically and a basolateral extracellular matrix (ECM)-like layer. The model produced tissues with morphologic and physiological resemblance to human cervical and vaginal epithelia, including mucus levels produced by cervical cells. Infection by Chlamydia trachomatis and Neisseria gonorrhoeae was demonstrated, as well as the growth of bacterial species observed in the human vaginal microbiota. This enabled controlled mechanistic analyses of the interactions between host cells, the vaginal microbiota and STI pathogens.

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Section: Resultssupporting

confidence: 88%

Three-dimensional models of the cervicovaginal epithelia to study host–microbiome interactions and sexually transmitted infections

Edwards

McComb

Gleghorn

et al. 2022

Pathogens and Disease

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show abstract

“…These results are similar to those observed in Buckner et al [46], where perceptible levels of IL-6, IL-8, IP10 and RANTES were detected. We observed that the cytokine response of the model in the presence or absence of a chlamydial infection was similar to that previously observed in this and other human and mouse cell lines [53][54][55][56]. These results indicate that the A2EN cervical epithelium 3D model could serve as a suitable platform for studies of chlamydial infection.…”

Section: D Cervical A2en Cells Are Infected By Chlamydia Trachomatis and Neisseria Gonorrhoeaesupporting

confidence: 87%

Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections

Edwards

McComb

Gleghorn

et al. 2021

Preprint

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Two-dimensional (2D) cell culture systems have provided controlled, reproducible means to analyze host-pathogen interactions. Although inexpensive, straightforward, and requiring very short time commitment, these models recapitulate neither the functionality of multi-layered cell types nor the microbial diversity of an infected human. Animal models have commonly been used to recreate the complexity of human infections. However, extensive modifications are commonly required to recreate interactions that resemble those in the human reproductive tract microbiologically and physiologically. Three-dimensional (3D) cell culture models have emerged as alternative means of reproducing key elements of human infections at a fraction of the cost of animal models and on a scale that allows for replicative experiments to be readily performed. Here we describe a new 3D model that utilizes transwells with epithelial cells seeded apically and a basolateral extra cellular matrix (ECM)-like layer containing collagen and fibroblasts. In this system, basal feeding creates a liquid/air interface on the apical side. The model produced tissues with close morphologic and physiological resemblance to human cervical and vaginal epithelia, including observable levels of mucus produced by cervical cells. Infection by both Chlamydia trachomatis and Neisseria gonorrhoeae was demonstrated as well as the growth of bacterial species observed in the human vaginal microbiota, enabling controlled mechanistic analyses of the interactions between host cells, vaginal microbiota and STI pathogens. Future experiments may include immune cells to mimic more closely the genital environment. Finally, the modular set up of the model makes it fully applicable to the analysis of non-genital host-microbiome-pathogen interactions.IMPORTANCEInfected sites in humans are a complex mix of host and microbial cell types interacting with each other to perform specific and necessary functions. The ability to understand the mechanism(s) that facilitate these interactions, and interactions with external factors is paramount to being able to develop preventative therapies. Models that attempt to faithfully replicate the complexity of these interactions are time intensive, costly, and not conducive to high throughput analysis. Two-dimensional (2D) models that have been used as a platform to understand these interactions, while cost effective, are generally limiting in experimental flexibility and structural/physiological relevance. Our three-dimensional (3D) models of the cervicovaginal epithelium can facilitate analysis of interactions between the host epithelium, sexually transmitted pathogens and bacteria present in the vaginal microbiota. Due to the modular design, additional cell types and environmental modulators can be introduced to the system to provide added complexity, approaching conditions in the infected human host.

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“…IL-6 is overexpressed in mice with Chlamydia-related tubal factor infertility or humans who suffered from Chlamydia-related disease (94,95). IL-6 can also be detected in the semen and serum of asymptomatic patients with Chlamydia infection (96,97). Elevated IL-6 levels were found to play a protective role in controlling Chlamydia infection, given that IL-6 deficient mice were significantly more susceptible to Chlamydia infection through the airway than wildtype mice (98,99).…”

Section: Il-6mentioning

confidence: 99%

Insights Into Host Cell Cytokines in Chlamydia Infection

Xiang

Lei

et al. 2021

Front. Immunol.

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Chlamydial infection causes a number of clinically relevant diseases and induces significant morbidity in humans. Immune and inflammatory responses contribute to both the clearance of Chlamydia infection and pathology in host tissues. Chlamydia infection stimulates host cells to produce a large number of cytokines that trigger and regulate host immune responses against Chlamydia. However, inappropriate responses can occur with excessive production of cytokines, resulting in overreactive inflammatory responses and alterations in host or Chlamydia metabolism. As a result, Chlamydia persists and causes wound healing delays, leading to more severe tissue damage and triggering long-lasting fibrotic sequelae. Here, we summarize the roles of cytokines in Chlamydia infection and pathogenesis, thus advancing our understanding chlamydial infection biology and the pathogenic mechanisms involved.

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Levels of different cytokines in women and men with asymptomatic genital infection caused by Chlamydia

Cited by 4 publications

References 18 publications

Three-dimensional models of the cervicovaginal epithelia to study host–microbiome interactions and sexually transmitted infections

Three-dimensional models of the cervicovaginal epithelia to study host–microbiome interactions and sexually transmitted infections

Three-dimensional models of the cervicovaginal epithelia to study host-microbiome interactions and sexually transmitted infections

Insights Into Host Cell Cytokines in Chlamydia Infection

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