Dr. Alex Hopke, an assistant professor in the Department of Biomedical Sciences, presented a poster titled “Caging Giants: Characterizing the Mechanisms by which Neutrophil Swarming Restricts Fungal Hyphae” at the Neutrophil International Symposium held September 17-19 in München, Germany.
Neutrophils can amplify their antimicrobial potency through swarming, a collective process that synchronizes the activities of multiple neutrophils against one target. The sequence of events contributing to swarming antifungal function has been recently characterized in some detail based on observations of neutrophils’ activities against clusters of fungi, specifically clusters of Candida albicans yeast. However, the relevance of these artificial yeast clusters to targets actually encountered during infection is unclear. Dr. Hopke explains, “Unfortunately, the swarming response directly against fungal hyphae, a larger fungal morphology important for virulence and invasion during infection, remains poorly characterized. To address this knowledge gap, we leveraged a microscale platform to probe the biology of human neutrophil swarming against arrays of C. albicans hyphae. Taking advantage of the ability to monitor large arrays of swarms, we quantified the effect of chemical inhibitors and receptor antagonists on different phases of human neutrophil swarming and how this impacted their ability to kill and restrict C. albicans hyphae. As examples, we found that both spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK) signaling plays a critical role in regulating human neutrophil swarming, with SYK or BTK inhibition severely impairing swarming responses and resulting in the significant loss of fungal restriction. Furthermore, we found a role for CD18 in allowing the swarm to effectively restrict these hyphae.” These findings advance the understanding of neutrophil swarming biology in humans and continue to build the foundation for understanding the role of neutrophil swarming in infection.
Dr. Hopke is a member of the Center of Excellence in Inflammation, Infectious Disease, and Immunity.