FIG 9.

Modeling chlamydial persistence in the context of infection. For stress conditions that do not affect PG synthesis and inclusion maturation (AMP and sucrose), C. trachomatis benefits from remaining intracellular but eventually will be targeted by cell-mediated killing mechanisms. Under stress conditions that halt PG synthesis and inclusion maturation (DPP, C1, and IFN-γ), the timing of induction directly affects the pathogen’s survival. If aberrance is induced early, prior to the establishment of the inclusion and the secretion of antiapoptotic factors, the microbe will be eradicated by either lysosomal fusion or host cell apoptosis. If aberrance is induced late in development, host cell processes such as chromosomal segregation and actin remodeling will be irreversibly affected, and immunostimulatory PG release will result in cytokine production, leading to cell-mediated killing. In this persistence model, Chlamydia survival is maximized when aberrance is induced subsequent to the host cell’s intracellular defenses being overcome but prior to the initiation of a cytokine-induced, innate immune response.