Date of Completion

12-29-2014

Embargo Period

12-27-2014

Keywords

Mycoplasma, Inflammation, Tracheal epithelial cell, TLR, LAMP

Major Advisor

Dr. Lawrence K. Silbart

Associate Advisor

Dr. Steven J. Geary

Associate Advisor

Dr. Paulo H. Verardi

Associate Advisor

Dr. Steven M. Szczepanek

Field of Study

Animal Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Mycoplasma gallisepticum infection in chickens is associated with severe inflammation of the trachea, air sacs and lungs. M. gallisepticum cytadheres to the tracheal epithelium and mediates infiltration of macrophages, heterophils and lymphocytes to the tracheal submucosa but the molecular mechanisms underpinning the severe inflammatory response is not well understood. This research focuses on identifying how M. galisepticum and chicken tracheal epithelial cell (TEC) interaction might contribute to this response. The first study identified that M. gallisepticum lipid associated membrane proteins (LAMP) from both virulent and non-virulent strains were able to up-regulate several inflammatory genes from tracheal epithelial cells both in vitro and ex vivo including, but not limited to IL-1β, IL-6, IL-8, IL-12p40, CCL-20 and NOS-2. However live virulent strains were significantly more efficient in not only up-regulating these genes to a greater extent but also differentially regulating several unique genes in TECs. The study also identified that M. gallisepticum LAMPs mediate the inflammatory gene up-regulation via TLR-2 ligation in an NF-κB dependent pathway. The second study identified, that interaction of a virulent strain with TECs leads to significantly more macrophage chemotaxis than a non-virulent strain. Macrophages upon co-culture with M. gallisepticum exposed TECs up-regulated expression of IL-1β, IL-6, IL-8, MIP-1β, CXCL-13, CCL-20 and RANTES. Interaction of Rlow ­with TECs enabled more efficient gene up-regulation from macrophages compared to Rhigh. Kinetic analysis of these genes identified the peak of expression of cytokine genes to be 6 hours reducing significantly thereafter, whereas expression of chemokine genes remained significantly above control level until 24 hours. These results further our understanding of molecular mechanisms leading to the severe inflammatory response observed during M. gallisepticum infection and suggest that interaction of M. gallisepticum with chicken tracheal epithelial cells play significant role in this process.

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