Co-expression network analysis reveals immune response pathways important for pathogenesis of Chlamydial pelvic inflammatory disease (PID). (HUM8P.329)

Abstract

Processes driving development of immune pathology after Chlamydia trachomatis infection are poorly understood. To provide insight into the pathways that may be underappreciated by individual gene analysis, weighted gene co-expression network analysis was performed to identify network modules using blood transcriptional profiles of women with chlamydial PID (N=15) and asymptomatically infected women (N=84). Modules, defined as centrally connected genes, that were significantly associated with chlamydial PID were further accessed via Ingenuity Pathway analysis. Type I and type II interferon (IFN) signaling pathways were significantly up regulated in women with chlamydial PID. Up regulation of both of these pathways has been detected in the transcriptomes of patients with active tuberculosis, suggesting a parallel role in PID. Up regulation of aryl hydrocarbon receptor, agranulocyte/granulocyte adhesion and diapedesis pathways was also noted, while EIF2/EIF4, mTOR and ILK signaling, granzyme A/B signaling, cross talk between dendritic cells and natural killer cells, signaling in T helper cells and T cell receptor pathways were down-regulated. Pathways likely to contribute to immunopathogenesis, including migration of leukocytes and inflammation were activated in chlamydial PID, while those involved in cell growth/proliferation and clearance of infected cells were decreased. Bioinformatics provides a new avenue to improve understanding of chlamydial disease mechanisms.