MACROPHAGE RECOGNITION AND PHAGOCYTOSIS OF RHODOCOCCUS

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Rhodococcus equi is a facultative intracellular bacteria that produces pulmonary abscessation and pneumonia. Formerly thought only to be a veterinary pathogen, it is now recognized as an agent of disease in immunocompromised persons such as those undergoing immunosuppressive therapy and those with Acquired Immunodeficiency Syndrome (AIDS). In the lung, the organism is typically found within alveolar macrophages, and several groups have shown that it multiplies within macrophages in vitro. The goal of this research is to define hte mechanism of interaction between Rhodococcus equi and macrophages. We propose to perform initial studies using the murine model and then to concentrate on human and equine models. Studies of other intracellular organisms have found that the fate of an intracellular microbe can be altered by changing the receptor that is responsible for microbial entry. Therefore, we plan to study the macrophage receptors involved in rhodococcus recognition, the physiology and molecular biology of these receptors, and the alteration of these receptors following immunologic activation. We also plan to quantitate the binding and intracellular fate of R. equi in macrophages with specific deletions in one or more of their complement receptors. Specifically, we will: 1. Characterize the binding of Rhodococcus equi to macrophages. 2. Study the cellular biology of R. equi phagocytosis by macrophages. 3. Use molecular biological techniques to further analyze the phagocytosis of R. equi by macrophages. 4. Perform in vivo experiments to study the pathobiology of R. equi. The specific aims of this proposal provide a challenging opportunity for me to investigate the interaction of a microbial agent with its host cell. With the guidance of prominent researchers, I will develop the research skills and learn an assortment of techniques which can be applied not only to R. equi but also to a variety of other intracellular pathogens. In addition to the proposed research, the Ph.D. degree program in which I am enrolled, at Temple University School of Medicine, includes formal coursework, laboratory training and seminars. It is may intention to use this intensive training period to become an independent researcher in the basic sciences.