Murine Oviduct Epithelial Cell Cytokine Responses toChlamydia muridarumInfection Include Interleukin-12-p70 Secretion

Abstract

Epithelial cells play an important role in host defense as sentinels for invading microbial pathogens.Chlamydia trachomatis is an intracellular bacterial pathogen that replicates in reproductive tract epithelium. Epithelial cells lining the reproductive tract likely play a key role in triggering inflammation and adaptive immunity during Chlamydia infections. For this report a murine oviduct epithelial cell line was derived in order to determine how epithelial cells influence innate and adaptive immune responses during Chlamydia infections. As expected, oviduct epithelial cells infected by Chlamydia muridarum produced a broad spectrum of chemokines, including CXCL16, and regulators of the acute-phase response, including interleukin-1␣ (IL-1␣), IL-6, and tumor necrosis factor alpha. In addition, infected epithelial cells expressed cytokines that augment gamma interferon (IFN) production, including IFN-␣/␤ and IL-12-p70. To my knowledge this is the first report of a non-myeloid/lymphoid cell type making IL-12-p70 in response to an infection. Equally interesting, infected epithelial cells significantly upregulated transforming growth factor alpha precursor expression, suggesting a mechanism by which they might play a direct role in the pathological scarring seen as a consequence of Chlamydia infections. Data from these in vitro studies predict that infected oviduct epithelium contributes significantly to host innate and adaptive defenses but may also participate in the immunopathology seen with Chlamydia infections.

The Chlamydia muridarum-Induced IFN-β Response Is TLR3-Dependent in Murine Oviduct Epithelial Cells

“…The cloned OE cell line Bm1.11 (10) was grown at 37˚C in a 5% CO 2 humidified incubator and maintained in epithelial cell media: 1:1 DMEM: F12K (Sigma-Aldrich), supplemented with 10% characterized FBS (ThermoFisher, Pittsburgh, PA), 2 mM L-alanyl-L-glutamine (GlutaMAX I; Life Technologies/Invitrogen, Carlsbad, CA), 5 mg bovine insulin/ml, and 12.5 ng/ ml recombinant human fibroblast growth factor-7 (keratinocyte growth factor; Sigma-Aldrich).…”

“…)C19 and OE129 WT, were prepared using a previously described procedure (10,12). Briefly, reproductive tract tissues from B6.129S1/j control and B6.129S1 TLR3 2/2 deficient female mice, encompassing a small cuff of the proximal uterine horn to the oviduct tissue immediately adjacent to the ovary, were harvested.…”

“…Epithelial cells lining mucosal surfaces serve as sentinels for invasion by microbial pathogens and are responsible for initiating the primary phases of the host immune response through the release of inflammatory cytokines during Chlamydia infections (7)(8)(9)(10). Because epithelial cells are likely the primary targets during infection with C. trachomatis, it is important to understand the cascade of events that results in the cytokine-mediated early immune response when these cells become infected.…”

“…Because epithelial cells are likely the primary targets during infection with C. trachomatis, it is important to understand the cascade of events that results in the cytokine-mediated early immune response when these cells become infected. To better understand the role of epithelial cells during immune responses to Chlamydia infections, we previously generated and characterized cloned murine oviduct epithelial (OE) cell lines (10). Those studies showed that Chlamydia-infected OE cells secreted chemokines involved in leukocyte recruitment (CCL5, CXCL1, CXCL9, and CXCL10) and cytokines involved in inflammation and shaping the adaptive immune response (IL-6, TNF-a, IFN-a/b, and IL-12 p 70 ).…”

Immune-mediated control of Chlamydia infection

“…Although epithelial cells are not classically considered critical players within the innate immune system, they are capable of initiating and propagating innate immune responses (Quayle, 2002). C. trachomatis infection of both human and murine epithelial cells can induce the production of pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, tumour necrosis factor-a (TNF-a) and Granulocyte-macrophage colony-stimulating factor (GM-CSF) (Rasmussen et al, 1997;Johnson, 2004). In addition, secretion of chemokines such as IL-8 by infected epithelial cells can recruit classical innate immune cells (Buchholz and Stephens, 2006).…”