Bacterial pathogens subvert host cells by manipulating cellular pathways for survival and replication; in turn, host cells respond to invading pathogens through cascading changes in gene expression. Deciphering this complex temporal and spatial interplay is crucial for improved diagnostics and therapeutics, as well as understanding fundamental biology.

Chlamydia are widespread bacterial pathogens that cause a range of mammalian diseases. The primary human chlamydial pathogen is C. trachomatis. It causes ocular and genital disease in mucosal epithelia across all socioeconomic groups, and is the most common human sexually transmitted bacterial infection (STI). Conversely, C. psittaci causes potentially lethal respiratory infections and is zoonotically acquired from infected birds.

We previously developed a novel dual RNA-Seq approach to simultaneously capture prokaryotic and eukaryotic expression profiles of bacteria-infected cells, using C. trachomatis-infected cells as proof of principle (1). We have significantly extended these results by performing dual RNA-Seq and time-matched miRNA-Seq to characterize the early infected host transcriptomes at 0.5, 1.5, 3, 6, and 12 hours post-infection in response to both C. trachomatis and C. psittaci infections. This dataset also includes time matched controls of mock-infected cells, UV-inactivated Chlamydia and opsonized latex beads for both RNA-Seq and miRNA-Seq data. With this data and controls, we have examined host cell differential mRNA and non-coding RNA expression, and patterns of alternate splicing, allowing a comprehensive definition of the host response to two chlamydial pathogens. We define a series of positive feedback mechanisms for Chlamydia-induced fibrotic scarring, the major disease outcome for C. trachomatis ocular and STD infections. In addition, despite the high degree of genomic similarity and phylogenetic relatedness of C. trachomatis and C. psittaci, the host response to each is dramatic and distinct, providing insight into the different disease outcomes of a mucosally-restricted STD and ocular pathogen versus a respiratory zoonotic pathogen.