Soman Abraham, PhD
Professor
Department of Pathology

The last century is notable for the remarkable successes made in the area of antibiotic and vaccine development against infectious agents. However, as we enter the beginning of the next century, the singular most common cause of morbidity and mortality in man and animals continues to be infectious diseases. With the anticipated growth in the aged and immunocompromised populations in our midst, there is an acute need for the development of alternate approaches to curb microbial infections and their harmful sequellae.

This laboratory is interested in studying the mechanisms and consequences of the molecular interactions occurring between pathogenic bacteria and inflammatory cells. We believe that there is a significant amount of crosstalk occurring between bacteria and immune cells of the host and the outcome dictates the pathology associated with bacterial infection as well as the survival of the pathogen in the host. We have focused our attention on the interactions between mast cells and gram negative enteric bacteria as a paradigm of host cell-pathogen crosstalk. We have recently discovered that mast cells are pivotal in initiating the host's inflammatory response to bacterial infection because of their ability to release various inflammatory mediators and their presence in large numbers in the skin, mucosal surfaces and around blood vessels.

A major focus of our studies is elucidating the molecular basis for mast cell-pathogen interactions with the goal of discovering how pathogens overcome or subvert the intrinsic anti-microbial activities of mast cells to cause disease. One mechanism employed by pathogenic bacteria appears to utilize distinct cellular entities called caveolae to enter mast cells via a route that avoids degradation in lysosomes. Thus, microbes entering mast cells via caveolae survive intracellularly and at the same time, avoid the antimicrobial actions of other immune cells and antibiotics. Caveolae are flask shaped invaginations rich in glycosphingolipids, cholesterol, and in a distinct protein, caveolin. Most host cells, including mast cells, produce caveolae. Although their physiological role in the cell is unclear, our studies with microbial pathogens suggest a novel endocytic function for these entities. Currently our studies are directed at: (i) identifying mast cell caveolar membrane components that mediate endocytosis of pathogens (ii) identifying specific caveolar components that protect invading pathogens from fusion with mast cell lysosomes and (iii) identifying some of the physiological activities of caveolae in mast cells.

Our work should have important implications in the understanding of hitherto poorly understood aspects of cell biology, the innate immune system and bacterial pathogenesis. These studies should facilitate the design of novel strategies that can selectively potentiate the microbicidal activity of inflammatory cells without increasing the harmful effects of inflammation.