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Novel Pathways Revealed in Bursa of Fabricius Transcriptome in Response to Extraintestinal Pathogenic Escherichia coli (ExPEC) Infection

ABSTRACT: Purpose: This study is to more comprehensively understand the genome-wide host response to avian pathogen E. coli (APEC). Methods: Four-week-old male broiler chickens were infected with APEC O1 or given saline as a control. Bursas were collected at 1 and 5 days post-infection (dpi). Infected birds were classified based upon lesions in liver, pericardium and air sacs as having mild or severe pathology, representing resistant and susceptible phenotypes, respectively. Twenty-two individual bursa RNA libraries were sequenced, each yielding an average of 27 million single-end, 100-bp reads. Results: There were 2469 novel genes in a total of 16,603 detected. Large numbers of significantly differentially expressed (DE) genes were enriched in susceptible versus resistant birds and in susceptible versus non-infected birds at 5 dpi, as well as in 5 dpi versus 1 dpi susceptible birds. The DE genes represented signal transduction, immune response, and cell growth and death pathways. Conclusions: These data provide considerable insight into potential mechanisms of resistance to ExPEC infection, thus paving the way to develop strategies for ExPEC prevention and treatment, as well as enhancing innate resistance by genetic selection in animals.

ORGANISM(S): Gallus gallus

PROVIDER: GSE70334 | GEO | 2017/02/09

SECONDARY ACCESSION(S): PRJNA288323

REPOSITORIES: GEO

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Project description:Purpose: This study is to more comprehensively understand the genome-wide host response to avian pathogen E. coli (APEC). Methods: Male broiler chicks were challenged with APEC (or mock-challenged as controls), and bone marrow was harvested at 1 and 5 days post-infection (dpi). Based upon necropsy-scored lesions on liver, pericardium, and air sacs, the challenged birds were assigned to mild or severe pathology categories, representing resistant and susceptible phenotypes, respectively. RNA sequence data were first analyzed using the R package EdgeR to identify differentially expressed genes.GO and pathway analysis using the R package GOseq identified many immune-related pathways. Results: RNA sequencing resulted in 11 to 40 million single-end raw reads of 100 bp per sample. After alignment, an average of 80 % of the reads, with 5 % representing multiple mapping, were mapped to the chicken reference transcriptome. Among these detected unique transcripts, there were 2,404 novel genes mainly distributed on chromosomes 1, 2, 4, 3, Z, 5 in decreasing number. Genes were detected as differentially expressed (DE) between treatments (susceptible, resistant, and mock-challenged) at a given time point, or DE between 1 and 5 dpi within the same treatment group. Compared to mock-challenged birds on 5 dpi, susceptible birds exhibited extensive enhancement of their T cell and B cell development, as well as innate and adaptive immune response. However, for the 1 dpi group, susceptible birds exhibited a decreased gene expression of T and B cell development. The differences between the two phenotypes, susceptible and resistant birds, at 5 dpi showed that susceptible birds had increased gene expression of B-cell development and adaptive immune response. Conclusions: This is the first report to our knowledge examining the role of bone marrow cells in responding to APEC infection in broilers. This transcriptome study provides insight and global overview into the response of genes involved in the earliest phases of the immune response to APEC infection. Our data indicate a dynamic interaction between the innate and adaptive immune responses to APEC infection in susceptible birds, providing flexibility and redundancy in the host’s induction of cytokines and chemokines. Additionally, B cell and T cell development are also extensively affected by APEC infection for susceptible birds, resulting in drastic host impairment in early response to infection. The findings of present study shed light on the underlying chicken immune modulation against APEC infection. Also, this study will build a solid foundation for identifying host genetic variation that may be manipulated to enhance resistance to infection and may be useful as colibacillosis control targets.

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Novel Pathways Revealed in Bursa of Fabricius Transcriptome in Response to Extraintestinal Pathogenic Escherichia coli (ExPEC) Infection

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