The role of innate immunity in the traumatic brain injury-induced immune suppression syndrome

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 DESCRIPTION (provided by applicant): Candidate: Dr. Schwulst is a trauma/critical care surgeon and Assistant Professor of Surgery at Northwestern University. He completed his general surgery residency, trauma/critical care fellowship, and research fellowship at Washington University, St. Louis. During his research fellowship, Dr. Schwulst studied the programmed cell death of lymphocytes during sepsis in the laboratory of Richard Hotchkiss. Since that time, Dr. Schwulst has published twelve manuscripts, three book chapters, numerous abstracts, and been awarded a US patent. His current career goals are to further advance the science behind injury with a particular focus on the innate immune response to traumatic brain injury (TBI). His long-term goal is to become a seasoned surgeon-scientist with both a fully funded laboratory and a robust trauma surgery and critical care practice. Environment: Northwestern University provides a comprehensive, interdisciplinary training program in modern immunology. Trainees are provided with flexibility to pursue individual research interests with strong mentorship from seasoned immunologists in diverse research fields. There are numerous immunology core facilities at Northwestern along with a state of the art animal facility. Additionally, his mentor's laboratory has its own 4-laser LSRII flow cytometer and 4 column Miltenyi magnetic separator. Research: TBI results in immune suppression leaving the host susceptible to secondary infection. In fact, infection is the leading cause of death following TBI. Preliminary data has shown that TBI results in a rapid and sustained loss of cells from the innate immune system as well as a shift towards an anti-inflammatory phenotype. Taken together, we hypothesize that monocytes and macrophages initiate the pathogenesis of TBI-induced immune dysfunction by creating and driving a systemic anti-inflammatory milieu resulting in increased infectious mortality after TBI. To test this hypothesis we have created a clinically applicable murine model of closed head injury to specifically interrogate the peripheral immune response to TBI. We aim to determine the role of monocytes and macrophages in the development of TBI-induced immune suppression, whether TBI drives the innate immune response towards an anti-inflammatory phenotype, and whether depletion of monocytes and macrophages decreases the susceptibility to secondary infections after TBI. To further these aims we will fully characterize the immune phenotype induced by our model via flow cytometry, cytokine analysis, and antibody production. Additionally, we will employ a series of monocyte/macrophage depletion experiments to further dissect their role in this process as well as a series of survival studies to determine if manipulation of the monocyte and macrophage populations affects the susceptibility of brain-injured animals to secondary pneumonia. Lastly, the effect of monocyte/macrophage depletion on cortical loss and neuronal degeneration after TBI will be assessed.