Wnt/Notch Crosstalk Promotes Epithelial-Mesenchymal Transition During Chlamydia trachomatis Infection Under IFN-γ Treatment.

Abstract

Chlamydia trachomatis (Ct) infection is a major cause of infertility, primarily through inducing tubal fibrosis. Epithelial-mesenchymal transition (EMT) plays a central role in this fibrotic process. However, the molecular mechanisms by which Ct infection triggers EMT are not fully understood. IFN-γ is a major component of the host immune pressure acting on infected epithelial cells during Ct infection. To mimic this immune environment in vitro and investigate how host signaling responses to Ct infection influence EMT, we maintained Ct-infected HeLa cells under continuous IFN-γ treatment and examined Wnt/β-catenin and Notch signaling. Under this condition, both pathways were activated and exhibited functional crosstalk potentially involving JAG1. Inhibition of either pathway attenuated EMT-associated phenotypes and was associated with reduced infectious progeny production. These findings support a role for Wnt/β-catenin-Notch crosstalk in promoting EMT in Ct-infected cells under continuous IFN-γ treatment.