Bovine Pathogenomics
Texas A&M University
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Faculty
 Dr. Terry Thomas
 Dr. Renee Tsolis
 Dr. Garry Adams
 Dr. Andreas Baumler
 Dr. Allison Rice-Ficht
 Dr. Thomas Ficht
 Dr. John Quarles
 Dr. James Womack

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About the Project

Texas A&M University is a leader in research on bovine genomics and bovine microbial pathogenesis models. We are a research team of investigators pursuing the objective to use the bovine model for dissecting innate immune responses to intracellular pathogens. The projects and investigators in our research program are:

 

Dr. James Womack: Genomic diversity in candidate genes for innate immunity.

 

Dr. Andreas J. Baumler: Mechanisms of innate immune recognition of S. Typhimurium.

 

Dr. Rene M. Tsolis: The role of the Brucella abortus type IV secretion in triggering host responses.

 

Dr. Allison Rice-Ficht: Mechanisms of innate immunity to Mycobacterium avium paratuberculosis.

 

Dr. L. Garry Adams: Director of in vivo bovine ligated ileal loop core laboratory.

 

Dr. Terry Thomas: Director, Genomics and bioinformatics core facility.

 

Dr. John M. Quarles: Director, Administrative support core.


Project Information

Why we use the calf as a model for human disease:

 

Innate immune recognition of microbes in the intestine is a pivotal step during host pathogen interactions that result in disease. The rationale for studying innate immune recognition is that a better understanding of the underlying molecular mechanisms will be required for developing innovative approaches for treatment or prevention of infections such as inflammatory diarrhea. Furthermore, detailed knowledge about the mechanisms involved in the normal regulation of intestinal inflammation will be required to fully understand disease states of uncontrolled inflammation, such as inflammatory bowel disease.

 

A current limitation for studying innate immunity is that the host response to infection observed in the most commonly used animal model, the mouse, differs dramatically from that observed in the human. For example, mice infected with Mycobacterium avium paratuberculosis develop a systemic infection while cattle develop a localized enteric infection that resembles inflammatory bowel disease (this pathogen has also been isolated from a subset of patients with Crohn's disease). Oral S. Typhimurium infection in mice results in intestinal inflammation characterized by a slowly developing mononuclear infiltrate which develops in the absence of diarrhea. In contrast, S. Typhimurium infections in calves and humans are characterized by a rapidly developing neutrophil infiltrate in the intestine that is always associated with diarrhea.

 

These data show that mice and humans exhibit strikingly different disease manifestations and host responses during infection with invasive enteric pathogens. Due to these limitations it is difficult to extrapolate data on the host response to enteric pathogens obtained using rodent models to human disease. In contrast, the striking similarities in the host responses of calf and human illustrate that the bovine host is an excellent model for studying responses observed in the intestine. Although the calf will not likely become a model used as widely as the mouse, characterization of the host response in calves is significant because it will provide insights into responses that cannot be studied using mice.

 

The bovine ligated ileal loop model allows the collection of samples at defined time points of up to 12 hours after infection, thereby providing a powerful tool for studying host pathogen interaction in vivo using a variety of techniques, including in situ hybridization, immunohistochemistry, histopathology, ultrastructural analysis and gene expression analysis using real-time polymerase chain reaction (RT-PCR), DNA microarrays or massive parallel signature sequencing (MPSS). With highly developed linkage and Riation Hybrid (HR) maps, a nearly completed whole-genome Bacterial Artificial Chromosome (BAC) map, sequences being available for genes involved in innate immunity and complete sequencing of its genome as a high priority at the NHGRI, the bovine is among the better genetically defined mammals, aside from humans and laboratory rodents.

 


Transmission Electron Micrograph of Brucella entering a macrophage


Massive proliferation of Brucella in a bovine macrophage


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