Date on Master's Thesis/Doctoral Dissertation
Microbiology and Immunology
Microbiology and Immunology, PhD
Committee Co-Chair (if applicable)
Abu Kwaik, Yousef
macrophage; neutrophil; host-pathogen; bacteria; effector; LTB4
Yersinia pestis has gained widespread infamy due to the historic outbreak during the middle ages, referred to as The Black Death. Infection with Y. pestis typically begins with deposition of Y. pestis into the dermis (bubonic plague) or respiratory tract (pneumonic plague). Tissue resident macrophages are the first innate immune cell encountered by Y. pestis. Macrophages are likely a way for Y. pestis to avoid neutrophils early in infection when the neutrophil neutralizing Type Three Secretion System is not expressed. This work focuses on which Rab host proteins are manipulated by Y. pestis, and how neutrophils are forced to remain silent when all alarms and the arsenal they possess should be triggered. Through an RNAi screen 8 Rab proteins were found to be important for intracellular Y. pestis survival. The Rab proteins were prioritized based on the impact gene knockdown had on Y. pestis intracellular survival. Overexpressed Rab2b and Rab20 co-localized to the YCV, while overexpressed Rab13 did not. Indicating Rab13 may regulate Y. pestis intracellular survival in a contact independent manner. Survival within macrophages likely provides Y. pestis time to express the type three secretion system. Using deletion and addition mutants, I found that Y. pestis uses the type three secretion system effectors, YopE, YopH, YopJ, and YpkA to inhibit neutrophil degranulation, in addition to inhibiting LTB4 production in human neutrophils also by YopT. Unlike human neutrophils, LTB4 is not produced in response to Y. pestis in mouse neutrophils or macrophages and the zinc binding protein, calprotectin is released in vivo, but not by human neutrophils. Together, the Rab data and neutrophil exocytic responses contribute to our understanding of how Y. pestis manipulates host phagocytic cells to create a permissive environment in which to survive and replicate.
Pulsifer, Amanda Rose, "Modulation of host innate immune cells by Yersinia pestis to create a permissive environment for replication." (2020). Electronic Theses and Dissertations. Paper 3384.