Spleen Tyrosine Kinase Is a Critical Regulator of Neutrophil Responses to <i>Candida</i> Species
Paige E. Negoro, Shuying Xu, Zeina Dagher, Alex Hopke, Jennifer L. Reedy, Michael B. Feldman, Nida S. Khan, Adam L. Viens, Natalie J. Alexander, Natalie J. Atallah, Allison K. Scherer, Richard A. Dutko, Jane Jeffery, John F. Kernien, J. Scott Fites, Jeniel E. Nett, Bruce S. Klein, Jatin M. Vyas, Daniel Irimia, David B. Sykes, Michael K. Mansour
Abstract
Neutrophils are recognized to represent significant immune cell mediators for the clearance and elimination of the human-pathogenic fungal pathogen Candida . The sensing of fungi by innate cells is performed, in part, through lectin receptor recognition of cell wall components and downstream cellular activation by signaling components, including spleen tyrosine kinase (Syk). While the essential role of Syk in macrophages and dendritic cells is clear, there remains uncertainty with respect to its contribution in neutrophils. In this study, we demonstrated that Syk is critical for multiple cellular functions in neutrophils responding to major human-pathogenic Candida species. These data not only demonstrate the vital nature of Syk with respect to the control of fungi by neutrophils but also warn of the potential infectious complications arising from the recent clinical development of novel Syk inhibitors for hematologic and autoimmune disorders.