While macrophages are normally considered to be a primary cell for mediating innate immune responses by phagocytosing and destroying microbes that infect mammals, some microbial organisms including bacteria and protozoa have specifically adapted themselves to survive and replicate in host cells thereby “hiding” from protective immune responses. We study Brucella abortus, a bacterium that causes disease in a wide variety of agricultural animals and in people, to evaluate how some animals but not others successfully prevent infections by intracellular pathogens. We are particularly interested in the role of host cytokines, such as interleukins and interferons produced by T lymphocytes, in controlling the infection through their ability to activate macrophages for antimicrobial activities. In addition we are interested in identifying genes of the bacteria that facilitate their survival in host macrophages thus allowing them to establish chronic infections. To do this we utilize gene knock-out mice and produce knock-outs of bacterial genes in conjunction with collaborators.
Our second major area of research evaluates gd T cells, a subpopulation of T lymphocytes that comprise a major proportion of lymphocytes in mammals but whose role in mediating protective immunity is unclear at this time. Currently my lab is ascertaining whether these cells have immunological memory, how this subpopulation of T lymphocytes is activated by constitutively expressed molecules on macrophages as well as by bacterial components and how macrophages regulate their response. Finally, we interested in the role of a lineage-specific cell-surface molecule of gd T cells, known as WC1, in signal transduction and activation.
Third, we are evaluating the role of cellular immune responses in protection of cattle against infections with the bacteria Leptospira borgpetersenii serovar hardjo. We are particularly interested in the unique role played by gamma delta T cells. Along with CD4 T cells, these cells exhibit recall responses in vaccinated cattle. That is, they produce interferon-gamma in response to stimulation with the bacterial antigens. Using microarray technology we are comparing genes expressed by gamma delta T cells vs CD4 T cells in response to antigen stimulation following vaccination as a mechanism to ascertain their unique role in protective immune responses.