Date of Completion

12-15-2017

Embargo Period

1-23-2018

Keywords

Mycoplasma, trachea, immune, host response, gallisepticum, vaccine, chicken, RNA-seq

Major Advisor

Dr. Steven J. Geary

Co-Major Advisor

Dr. Lawrence K. Silbart

Associate Advisor

Dr. Steven M. Szczepanek

Field of Study

Pathobiology

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Chickens infected with Mycoplasma gallisepticum, the primary etiologic agent of chronic respiratory disease (CRD), present with significant respiratory complications. The host response is often immunopathogenic and contributes to increased tracheal thickness due to the chemotaxis of leukocytes, cellular damage at the mucosal surface, and the inability to clear the infection. The response to M. gallisepticum is complex and the differences that lead to a maladaptive versus beneficial response are poorly understood. To elucidate the extent of the host response to virulent and attenuated strains, we conducted next-generation sequencing on samples taken directly from the host’s tracheal mucosa after infection with either virulent Rlow, or laboratory attenuated vaccine strains Mg 7 or GT5.

In the first study, transcriptional analysis of the host response to virulent Rlow over a 7-day infection was conducted on samples from days 1, 3, 5 and 7. Data indicated a rapid, pro-inflammatory response, identifying numerous genes involved in immune pathways that peaked 3 days post-infection, and a significant metabolic response observed on days 1 and 3. Further analysis revealed increased expression of host cell receptors that likely heightens their sensitivity to damage- and pathogen- associated molecular patterns and results in the production of cytokines and chemokines that recruit and activate immune cells.

In the second study, comparative transcriptomics identified differences between the early host response to Rlow and laboratory vaccine strains, Mg 7 and GT5. Infection with these attenuated strains resulted in a dampened host response involving significantly fewer immune and metabolism-related genes, limited differential expression of host cell receptors, and decreased production of cytokines and chemokines. Future vaccines should aim to target immune genes active in Mg 7 and GT5 infection while avoiding those uniquely differential in Rlow infection to induce a protective, and durable adaptive response while avoiding immune-related exacerbation of disease.

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