Thymus Transcriptome Reveals Novel Pathways in Response to Avian Pathogenic Escherichia coli (APEC) Infection. Gallus gallus

Purpose: This study would be useful to characterize the molecular mechanisms of an effective anti-bacterial response of chicken immune system. Methods: meat-type chickens were either infected with APEC O1 or given saline as a control. Thymii were collected on 1 and 5 days post-infection (dpi). The infected birds were classified based upon necropsy findings as having mild or severe pathology, representing resistant and susceptible phenotypes, respectively. Data from RNA sequencing experiments were analyzed using the R package, edgR, to identify the significantly differentially expressed (DE) genes. GO and pathway analysis using the R package GOseq identified many immune-related pathways. Results: Thousands of genes were DE at 5 dpi in susceptible vs. non-infected birds and in susceptible vs. resistant birds, as well as in susceptible birds at 1 vs. 5 dpi. In the contrast of susceptible birds with resistant or non-challenged birds, many immune response and signal transduction pathways were strongly induced, whereas the TCR signaling pathway was deeply suppressed to affect T cell development, differentiation, proliferation, and maturation. The transcriptomes of resistant and non-challenged birds were similar. Conclusions: These results provide the first comprehensive assessment of global gene networks and biological functionalities of DE genes in thymus in response to APEC infection, thus providing novel insights into key molecular genetic mechanisms that differentiate host resistance from susceptibility in this primary lymphoid tissue. These findings are foundational to the development of strategies to enhance host resistance to APEC infection. Overall design: Thymus mRNA profiles of six treatment groups were generated by deep sequencing, in four replicates, using Illumina Hiseq2000.