Pulmonary innate immunity and pathogens of the order Actinomycetales

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DESCRIPTION (provided by applicant): THE CANDIDATE: Dr. Tracy Carlson, a licensed veterinarian with board-eligibility in veterinary anatomic pathology, is completing a Ph.D. training program at the Ohio State University (OSU). The K01 SERCA will support her training and progression to scientific independence. THE ENVIRONMENT: OSU has an extensive biomedical research complex including state of the art core facilities in the Colleges of Medicine / Veterinary Medicine. Dr. Larry Schlesinger, the Principal Investigator's mentor, is the Director of both the Infectious Disease Division and the Center for Microbial Interface Biology. Dr. Schlesinger is an experienced mentor in the training of Ph.D. students and K award trainees. THE TRAINING PLAN: The first year of the K award will be used to support the completion of the Ph.D. training of Dr. Carlson in a mentored environment in Dr. Schlesinger's laboratory. The last four years will be used to facilitate Dr. Carlson's transition to an independent researcher following the plan outlined in the research proposal. This will foster eligibility for employment in competitive staff and faculty scientist positions. THE RESEARCH: The initial interaction of respiratory pathogens with the innate immune system is critical for determining the outcome of disease particularly for bacteria of the order Actinomycetales, such as Mycobacteria and Rhodococcus spp., which have the ability to live in innate immune cells (alveolar macrophages). Interaction of the local lung environment, in particular surfactant protein D, has antimicrobial effects on Mycobacterium tuberculosis in in vitro assays. In this research proposal we will further define the interaction of SP-D with M. tuberculosis and the effect it has on the survival of the bacteria in in vitro assays and in vivo in part by exploring the effect of SP-D mutations on the outcome of infection. Additional research will focus on the pulmonary host response to the related Rhodococcus equi, a bacterium that is a significant source of opportunistic pulmonary disease in immunocompromised (AIDS) patients as well as being an important cause of economic loss and morbidity as a disease of young horses. Defining and modulating the interaction of the pulmonary environment with these pathogens will open new avenues of investigation into potential targeted immunotherapies. PUBLIC HEALTH RELEVANCE: Tuberculosis is one of the leading causes of death due to a single infectious disease agent and infects ~ 1/3 of the world's population. The related Rhodococcus equi is an opportunistic infection in AIDS patients and a cause of economic loss / morbidity in the equine industry. Our project will define the initial interaction of these bacteria with the lung innate immune system and generate novel approaches to immunotherapy.