Stromal Fibroblasts Drive Host Inflammatory Responses That Are Dependent on Chlamydia trachomatis Strain Type and Likely Influence Disease Outcomes

Autor: Deborah Dean, Ekhlas Ahmed Abdulraheem, Sameeha Rau, Amber L. Jolly, Anmol K. Chadha
Přispěvatelé: Nacy, Carol A
Rok vydání: 2019
Předmět:
Chemokine
medicine.medical_treatment
Chlamydia trachomatis
primary human epithelial cells
medicine.disease_cause
immune response
2.2 Factors relating to the physical environment
2.1 Biological and endogenous factors
Aetiology
Macrophage inflammatory protein
Cells
Cultured

0303 health sciences
Cultured
biology
QR1-502
3. Good health
Cytokine
Infectious Diseases
Chemokine secretion
Host-Pathogen Interactions
Cytokines
Infection
Research Article
Stromal cell
sexually transmitted diseases
Cells
primary human stromal fibroblasts
Microbiology
Host-Microbe Biology
Proinflammatory cytokine
03 medical and health sciences
Immune system
Clinical Research
Virology
medicine
Humans
Eye Disease and Disorders of Vision
030304 developmental biology
Inflammation
030306 microbiology
Inflammatory and immune system
Epithelial Cells
Fibroblasts
Chlamydia Infections
trachoma
Good Health and Well Being
strain types
Immunology
biology.protein
Sexually Transmitted Infections
Zdroj: mBio, vol 10, iss 2
mBio
mBio, Vol 10, Iss 2, p e00225-19 (2019)
mBio, Vol 10, Iss 2 (2019)
Popis: 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.
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.
Databáze: OpenAIRE