Research

The broad goal of efforts in my laboratory is to understand the infectious process whereby parasites gain access to and cause disease in their hosts.

Current projects involve exploring the role of the immune system in controlling and modulating the outcome of compound infections with intracellular agents (bacteria) and extracellular agents (gastrointestinal nematode parasites). In nature, most animals are continually bombarded with infectious agents that can lead to life-threatening pathology. Recent developments suggest that the immune system regulates the outcome of infections via secreted protein products called cytokines. When an individual is infected with a pathogen, there is an early event mediated by T helper cells that determines whether that individual will develop serious pathology or will heal. T helper cells can be further subdivided into T helper 1 and T helper 2 subpopulations. Infection of an individual with intracellular bacterial, viral, or protozoal pathogens stimulates T helper 1 cells to elaborate cytokines that help the immune system to heal these infections. In contrast, infection of an individual with nematode parasites stimulates T helper 2 cells to produce cytokines and an immune response that heals these infections. The most surprising new finding is that selection of a positive response to a nematode pathogen down regulates the effector responses of the other pathway, thus leaving the host susceptible to the adverse effects of intracellular pathogens. The reverse also seems to occur. Therefore, a healthy response against one agent may mean a failed response against another.

We have developed an animal model to explore this concept along with new molecular reagents that will enable us to test this theory and apply it to the pathogenesis of infectious agents of concern to human and animal health. Unraveling of the intricate interplay between these predominant cytokine pathways may lead to improved understanding of regulatory mechanisms of the immune system and suggest better strategies for vaccination and disease prevention.

Publications

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