Transcriptional Profiling of the Chicken Tracheal Response to Virulent Mycoplasma gallisepticum Strain R low

Mycoplasma gallisepticum , the primary etiologic agent of Chronic Respiratory Disease (CRD) in poultry, leads to prolonged recruitment and activation of inflammatory cells in the respiratory mucosa. This is consistent with the current model of immune dysregulation that ostensibly allows the organism to evade clearance mechanisms and establish chronic infection. To date, studies using qRT-PCR and microarrays have shown a significant transient up-regulation of cytokines and chemokines from tracheal epithelial cells (TECs) in vitro and tracheal tissue ex vivo in response to virulent strain R low , that contributes to the infiltration of inflammatory cells into the tracheal mucosa. To expand upon these experiments, RNA was isolated from tracheas of 20 chickens infected with M. gallisepticum R low and 20 mock-infected animals at days 1, 3, 5 and 7 post inoculation, and analyzed for differential gene expression using Illumina RNA sequencing. A rapid host response was observed 24 hours post-infection, with over 2,500 significantly differentially expressed genes on day 3, the peak of infection. Many of these genes have immune related functions involved in signaling pathways including the TLR, MAPK, Jak-STAT, and the NOD-Like Receptor. Of interest, was the increased expression of numerous cell-surface receptors including TLR-4 and -15 which may contribute to the production of cytokines. Metabolic pathways were also activated on days 1 and 3 post-infection, ostensibly due to epithelial cell distress that occurs upon infection. Early perturbations in tissue-wide gene expression, as observed here, may underpin a profound immune dysregulation, setting the stage for disease manifestations characteristic of M. gallisepticum infection.