BABESIA-SECRETED EXTRACELLULAR VESICLES MODULATE HOST IMMUNE CELL RESPONSES

Human babesiosis is an emerging infectious disease caused by a bloodborne unicellular parasite called Babesia. Cases of human babesiosis are commonly reported in the United States, Western Europe, and Asia and typically present with flu-like symptoms such as fever, chills, and nausea. One of the major species of Babesia that infect humans is Babesia microti which is transmitted to humans through tick bites during a bloodmeal. As a successful pathogen, Babesia has evolved mechanisms to evade and manipulate the human immune system, ensuring successful development and proliferation. One such mechanism is the secretion of extracellular vesicles (EVs). The inhibition of the secretion of these vesicles may lead to disease control. One potential inhibitor of extracellular vesicle secretion is linoleic acid, a poly-unsaturated lipid that has demonstrated inhibitory properties in other parasites. To study the effects of development stage-dependent stimulus on Babesia duncani, we also examined the use of sorbitol, a sugar alcohol, to synchronize parasites. Currently, little is known about the interactions between these secreted EVs and the major players of the human immune system. Our research focuses on elucidating the relationship between EVs secreted by B. microti and isolated neutrophils. Neutrophils are one of the major white blood cells (WBCs) involved in innate immunity and act as first responders, accounting for approximately 70% of all WBCs in circulation. Neutrophils possess mechanisms to protect the host such as cytokine secretion and the release of neutrophil extracellular traps (NETs) in a process known as NETosis. NETs consist of the neutrophil’s DNA and are loaded with bound granules such as myeloperoxidase (MPO). We hypothesize that the signaling mechanisms of isolated neutrophils can be activated and modulated by EVs secreted by B. microti, contributing to successful infection. Confirmed by measuring concentrations of MPO and scanning electron microscopy (SEM), we have shown that isolated EVs from Babesia microti induce NETosis in neutrophils derived from mice.