Graduate Group in Comparative Pathology at UC Davis
Graduate Student Profile

Eduardo Cobo, DVM
FOOD ANIMAL HEALTH
Cellular and humoral immune response in the genital tract of bulls infected with extracellular pathogens

Why I
Joined GGCP

In my country, Argentina, I did my DVM and a doctorate in veterinary science studying bovine venereal diseases. However, after that, I realized that I wanted to enter a PhD program focused on the study of disease pathogenesis at cellular and molecular levels. Thus, supported by Fulbright, I applied to the UC Davis GGCP because it is one of the most well-recognized graduate programs in this subject. In addition, GGCP offers a great network of science disciplines from which one can interchange and learn. In my case, focused on the genital immune response in bulls, I can say that GGCP allows me to study the continuum from the "macro" bull to the "micro" genomic expression of genital tract cells and everything in between. This "three-dimensional" studying process is possible because GGCP has internationally recognized researchers in different areas of biology, including pathology, immunology, theriogenology, and microbiology. The UC Davis campus offers housing facilities that are specialized for farm animals and numerous sophisticated labs in which one can perform research under near-ideal conditions. In addition to these research resources, the courses offered through GGCP are up to date and diverse, allowing for a superior education. Summarizing, GGCP is a friendly though challenging graduate group within which there are unique opportunities to succeed.


My Research

My long-term goal is to define the general mucosal immune response in bulls' lower genital tract that allows pathogenic microorganisms to persistently infect. This is a basic immunology approach that focuses on local cellular and humoral responses and the triggered cytokine environment using as a model two phylogenetically very different obligate extracellular pathogens of the bovine genital mucosa (a parasite, T. foetus, and a bacteria, C. fetus venerealis). In this PhD project, we hypothesize that the mucosal immunity of the bovine male lower genital tract, when locally stimulated by extracellular mucosal-specific T. foetus and/or C. fetus, responds in an immunosuppressive fashion that allows persistent colonization.

This genital immunosuppression is characterized by an increase in secretions of protein and mRNA expression of suppressor IL-10 and TGF-beta cytokines in mucosa. In addition, the protein level and mRNA expression of proinflammatory TNF-alpha and IFN-gamma cytokines are not altered or reduced. On the other hand, a shift in the magnitude of response of CD4+, CD8+, delta-gamma T cells, eosinophils, plasma cells, and mast cells in mucosa and submucosa occurs after local mucosal stimulation.

At this time, mature bulls are being locally inoculated with T. foetus and/or C. fetus and some are additionally systemically vaccinated with T. foetus antigens. Groups of bulls are being slaughtered at six or nine weeks after inoculation or vaccination. Persistence of T. foetus and C. fetus venerealis, specific antibody responses in genital secretions and sera, histological alterations of genital tissues, and local cytokine protein levels and mRNA expression are being determined.

The project is justified because there is no complete immunological study of bovine male genitalia, and the distribution, phenotype, and function of mucosal immune cells have not been identified. Moreover, the pathogenesis in bulls of sexually transmitted diseases (STDs) and the mechanism by which the few commercially available vaccines for those diseases aid in clearing of already infected bulls are unknown. Confirmation of a mucosal immunosuppression in bull genitalia under local stimulation would provide essential information for determining the pathogenesis of STDs and developing effective vaccines for them.