Center for Comparative Medicine

Lyme Disease

Lyme disease is a tick-borne infectious disease of humans and animals. Inoculation of Borrelia burgdorferi into laboratory mice results in development of arthritis, carditis and neurologic disease within the first few weeks of infection. Arthritis and carditis resolve and recur episodically over the course of persistent infection. These are key features of Lyme disease in humans and some domestic animals (dogs, horses, etc.). Despite persistent infection, infected hosts (mice, dogs and humans) develop protective and disease-resolving immune responses that are B cell-mediated and T cell-independent. Using the mouse model, Dr. Barthold’s group has discovered that B. burgdorferi up-regulates several key antigens within the feeding tick and in vivo during the course of infection, and these antigens are the principal targets for protective and disease-resolving immune responses. Because these biologically relevant immune responses are B cell-mediated, a B. burgdorferi genomic expression library is being screened with serum from infected mice. The group has incriminated, cloned and expressed key antigens that elicit either protective immunity or arthritis-resolving immunity. Using the mouse model, the group is also investigating deleterious immune reactions that elicit autoimmunity, which are suspected in chronic Lyme disease patients, as well as mechanisms by which B. burgdorferi evades immune clearance. Dr. Barthold has utilized the mouse model to develop and test a recombinant outer surface protein A (OspA) vaccine that has been proven to be efficacious in mice, dogs and humans.

Bartonella henselae. Domestic cats serve as major reservoir hosts for this bacterium, which is transmitted among cats through fleas. Humans infected with this bacterium can develop a number of clinical manifestations, which are particularly significant in persons with depressed immune responses. Using serum from infected cats and mice, a genomic expression library is being probed to reveal immunogenic antigens that may function in host immunity. The antigens derived from this effort will have potential as recombinant antigens for diagnostic use, or as vaccines in cats. Vaccination of cats would be a useful means of protecting persons at risk for exposure.

Murine Helicobacter Infection

Laboratory mice are prone to infection with a number of different species of Helicobacter, which generally colonize the hind gut. Selected inbred strains of mic, and mice with altered immunity, are prone to development of proliferative intestinal disease when infected with Helicobacters. Dr. Barthold's laboratory is investigating novel means of diagnosing Helicobacter infections, and understanding the dynamics of infection with these bacteria in immunocompetent and immunodeficient mice.

Mouse Biology

In addition to serving as Director of the CCM, Dr. Barthold is Director of the UCD Mouse Biology Program (see Mouse Biology Program), which is administered by the CCM. Dr. Barthold is Principal Investigator of an NIH Mutant Mouse Regional Resource Center grant. As part of the Mouse Biology Program, Dr. Barthold’s laboratory is engaged in development of recombinant diagnostic antigens and improved serologic assays for laboratory mouse infectious disease diagnostics.