Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes

ABSTRACT Chlamydia trachomatis ocular strains cause a blinding disease known as trachoma. These strains rarely cause urogenital infections and are not found in the upper genital tract or rectum. Urogenital strains are responsible for a self-limited conjunctivitis and the sequelae of infertility, ect...

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Autores principales:	Amber Leah Jolly, Sameeha Rau, Anmol K. Chadha, Ekhlas Ahmed Abdulraheem, Deborah Dean
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Chlamydia trachomatis immune response primary human epithelial cells primary human stromal fibroblasts sexually transmitted diseases strain types Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1a61aa51d3a64520be8d4aaa913d1a43
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spelling	oai:doaj.org-article:1a61aa51d3a64520be8d4aaa913d1a432021-11-15T15:55:24ZStromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes10.1128/mBio.00225-192150-7511https://doaj.org/article/1a61aa51d3a64520be8d4aaa913d1a432019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00225-19https://doaj.org/toc/2150-7511ABSTRACT Chlamydia trachomatis ocular strains cause a blinding disease known as trachoma. These strains rarely cause urogenital infections and are not found in the upper genital tract or rectum. Urogenital strains are responsible for a self-limited conjunctivitis and the sequelae of infertility, ectopic pregnancy, and hemorrhagic proctitis. However, the differential cellular responses that drive these clinically observed disease outcomes are not completely understood. Primary conjunctival, endocervical, and endometrial epithelial and stromal fibroblast cells, HeLa229 cells, and immortalized conjunctival epithelial (HCjE) cells were infected with the ocular A/Har-13 (A) and Ba/Apache-2 (Ba) strains and urogenital D/UW-3 (D) and E/Bour (E) strains. Infection rates, progeny production, and cytokine/chemokine secretion levels were evaluated in comparison with those in uninfected cells. All strain types infected all cell types with similar levels of efficacy and development. However, progeny production levels differed among primary cells: Ba produced significantly more progeny than E in endocervical and endometrial fibroblasts, while A progeny were less abundant than E progeny. C. trachomatis infection of primary epithelial cells elicited an increase in pro- and anti-inflammatory mediators compared to levels in uninfected cells, but there were no significant differences by strain type. In contrast, for primary fibroblasts, ocular strains elicited significant increases in the pro- and anti-inflammatory mediators macrophage inflammatory protein (MIP)-1β, thymus- and activation-regulated chemokine (TARC), interleukin (IL)-2, IL-12p70, and interferon gamma-induced protein 10 (IP-10) compared to levels in urogenital strains, while urogenital strains elicited a distinct and significant increase in the proinflammatory mediators IL-1α, IL-1β, IL-8, gamma interferon (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Our data indicate that primary fibroblasts, not epithelial cells, drive host inflammatory responses that are dependent on strain type and likely influence disease outcomes, establishing their importance as a novel model for studies of C. trachomatis disease pathogenesis. IMPORTANCE Chlamydia trachomatis is a human pathogen and the leading cause of preventable blindness and sexually transmitted diseases in the world. Certain C. trachomatis strains cause ocular disease, while others cause upper genital tract pathology. However, little is known about the cellular or immunologic basis for these differences. Here, we compared the abilities of the strain types to infect, replicate, and initiate an immune response in primary human ocular and urogenital epithelial cells, as well as in fibroblasts from the underlying stroma. While there were no significant differences in infection rates or intracellular growth for any strain in any cell type, proinflammatory responses were driven not by the epithelial cells but by fibroblasts and were distinct between ocular and urogenital strains. Our findings suggest that primary fibroblasts are a novel and more appropriate model for studies of immune responses that will expand our understanding of the differential pathological disease outcomes caused by various C. trachomatis strain types.Amber Leah JollySameeha RauAnmol K. ChadhaEkhlas Ahmed AbdulraheemDeborah DeanAmerican Society for MicrobiologyarticleChlamydia trachomatisimmune responseprimary human epithelial cellsprimary human stromal fibroblastssexually transmitted diseasesstrain typesMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chlamydia trachomatis immune response primary human epithelial cells primary human stromal fibroblasts sexually transmitted diseases strain types Microbiology QR1-502
spellingShingle	Chlamydia trachomatis immune response primary human epithelial cells primary human stromal fibroblasts sexually transmitted diseases strain types Microbiology QR1-502 Amber Leah Jolly Sameeha Rau Anmol K. Chadha Ekhlas Ahmed Abdulraheem Deborah Dean Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes
description	ABSTRACT Chlamydia trachomatis ocular strains cause a blinding disease known as trachoma. These strains rarely cause urogenital infections and are not found in the upper genital tract or rectum. Urogenital strains are responsible for a self-limited conjunctivitis and the sequelae of infertility, ectopic pregnancy, and hemorrhagic proctitis. However, the differential cellular responses that drive these clinically observed disease outcomes are not completely understood. Primary conjunctival, endocervical, and endometrial epithelial and stromal fibroblast cells, HeLa229 cells, and immortalized conjunctival epithelial (HCjE) cells were infected with the ocular A/Har-13 (A) and Ba/Apache-2 (Ba) strains and urogenital D/UW-3 (D) and E/Bour (E) strains. Infection rates, progeny production, and cytokine/chemokine secretion levels were evaluated in comparison with those in uninfected cells. All strain types infected all cell types with similar levels of efficacy and development. However, progeny production levels differed among primary cells: Ba produced significantly more progeny than E in endocervical and endometrial fibroblasts, while A progeny were less abundant than E progeny. C. trachomatis infection of primary epithelial cells elicited an increase in pro- and anti-inflammatory mediators compared to levels in uninfected cells, but there were no significant differences by strain type. In contrast, for primary fibroblasts, ocular strains elicited significant increases in the pro- and anti-inflammatory mediators macrophage inflammatory protein (MIP)-1β, thymus- and activation-regulated chemokine (TARC), interleukin (IL)-2, IL-12p70, and interferon gamma-induced protein 10 (IP-10) compared to levels in urogenital strains, while urogenital strains elicited a distinct and significant increase in the proinflammatory mediators IL-1α, IL-1β, IL-8, gamma interferon (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Our data indicate that primary fibroblasts, not epithelial cells, drive host inflammatory responses that are dependent on strain type and likely influence disease outcomes, establishing their importance as a novel model for studies of C. trachomatis disease pathogenesis. IMPORTANCE Chlamydia trachomatis is a human pathogen and the leading cause of preventable blindness and sexually transmitted diseases in the world. Certain C. trachomatis strains cause ocular disease, while others cause upper genital tract pathology. However, little is known about the cellular or immunologic basis for these differences. Here, we compared the abilities of the strain types to infect, replicate, and initiate an immune response in primary human ocular and urogenital epithelial cells, as well as in fibroblasts from the underlying stroma. While there were no significant differences in infection rates or intracellular growth for any strain in any cell type, proinflammatory responses were driven not by the epithelial cells but by fibroblasts and were distinct between ocular and urogenital strains. Our findings suggest that primary fibroblasts are a novel and more appropriate model for studies of immune responses that will expand our understanding of the differential pathological disease outcomes caused by various C. trachomatis strain types.
format	article
author	Amber Leah Jolly Sameeha Rau Anmol K. Chadha Ekhlas Ahmed Abdulraheem Deborah Dean
author_facet	Amber Leah Jolly Sameeha Rau Anmol K. Chadha Ekhlas Ahmed Abdulraheem Deborah Dean
author_sort	Amber Leah Jolly
title	Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes
title_short	Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes
title_full	Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes
title_fullStr	Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes
title_full_unstemmed	Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes
title_sort	stromal fibroblasts drive host inflammatory responses that are dependent on <named-content content-type="genus-species">chlamydia trachomatis</named-content> strain type and likely influence disease outcomes
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/1a61aa51d3a64520be8d4aaa913d1a43
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Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on <named-content content-type="genus-species">Chlamydia trachomatis</named-content> Strain Type and Likely Influence Disease Outcomes

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