William Nauseef, MD, Professor in Infectious Diseases and of Microbiology and Immunology, has been awarded a five-year, $2.6M grant from the National Institutes of Health. This R01 will fund his lab’s continuing research into neutrophil-mediated responses to inflammation and host responses to infection. Dr. Nauseef explains more specifically:
The work proposes studies using Staphylococcus aureus and Neisseria gonorrhoeae as tools to interrogate signaling pathways that control neutrophil survival and cell death. There are two aims: (1) to determine the mechanisms that regulate human PMN fate and (2) to determine the mechanisms underlying hPMN secretion of IL-1b during phagocytosis.
We will elucidate fundamental aspects of human neutrophil biology that figure prominently in the resolution of the human inflammatory response. An effective immune system must both respond to threats and also restore tissue homeostasis. Despite critical links between innate immune cell fate and the timely resolution of inflammation, the crosstalk in molecular signaling among the pathways towards survival, apoptosis, and necrotic cell death is complex and incompletely understood. Activated human PMN and their secreted products sculpt the inflammatory tone in tissue, and failure of human PMN to undergo apoptotic cell death derails the resolution phase of the inflammatory response and instead amplifies disease. We reason that elucidation of the biochemical determinants that dictate human PMN fate after phagocytosis will provide fundamental insights into the mechanisms driving them towards survival vs programmed cell death pathways. Findings from our proposed work will illuminate fundamental aspects of inflammation, with special focus on phagocytosis-induced human PMN death pathways and IL-1b secretion. From this perspective, understanding mechanisms for resolution of inflammation and restoration of homeostasis will provide a framework to inspire novel therapeutic interventions in a wide range of clinical settings.
Dr. Nauseef is one of the members of the Iowa Inflammation Program, a multi-disciplinary team of researchers contributing to a deeper understanding of the mechanisms, causes, and consequences of inflammation.