AbstractHuman babesiosis is an emerging infectious disease caused by a bloodborne unicellular parasite called Babesia. One of the major species of Babesia that infects humans is Babesia microti, which is transmitted through tick bites during a blood meal. As a successful pathogen, Babesia has evolved mechanisms to evade and manipulate the human immune system, ensuring effective development and proliferation. One such mechanism is the secretion of extracellular vesicles. While extracellular vesicles have been shown to regulate host-pathogen interactions in related intracellular parasites, their role in modulating neutrophil responses during babesiosis remains unexplored. Neutrophils are a major white blood cell 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 consisting of the neutrophil's DNA, which have bound granules, such as myeloperoxidase, in a process known as NETosis. Here, we investigated the effect of Babesia microti- derived EVs using isolated mouse neutrophils and co-culture assays to assess cytokine secretion and NET formation. We found that Babesia microti EVs robustly trigger NETosis and activate the secretion of key inflammatory cytokines. Collectively, these findings reveal a previously uncharacterized role for Babesia microti EVs in modulating host neutrophil activity, providing mechanistic insight into host-parasite interactions during babesiosis, highlighting the importance of EV-mediated signaling in the pathogenesis of B. microti infection.
Simone et al. (Fri,) studied this question.