Neutrophils kill the parasite Trichomonas vaginalis using trogocytosis

摘要

T . vaginalis , a human-infective parasite, causes the most common nonviral sexually transmitted infection (STI) worldwide and contributes to adverse inflammatory disorders. The immune response to T . vaginalis is poorly understood. Neutrophils (polymorphonuclear cells [PMNs]) are the major immune cell present at the T . vaginalis –host interface and are thought to clear T . vaginalis . However, the mechanism of PMN clearance of T . vaginalis has not been characterized. We demonstrate that human PMNs rapidly kill T . vaginalis in a dose-dependent, contact-dependent, and neutrophil extracellular trap (NET)-independent manner. In contrast to phagocytosis, we observed that PMN killing of T . vaginalis involves taking “bites” of T . vaginalis prior to parasite death, using trogocytosis to achieve pathogen killing. Both trogocytosis and parasite killing are dependent on the presence of PMN serine proteases and human serum factors. Our analyses provide the first demonstration, to our knowledge, of a mammalian phagocyte using trogocytosis for pathogen clearance and reveal a novel mechanism used by PMNs to kill a large, highly motile target. Author summary The human parasite Trichomonas vaginalis is a large unicellular, motile eukaryote that causes a highly prevalent sexually transmitted infection in humans: trichomoniasis. While harmful effects of trichomoniasis are associated with inflammation, the immune response to the parasite is sorely under-characterized. Neutrophils are known to be important players in the host response to T . vaginalis , but it was not previously known how effective they are at killing the parasite and the mechanism(s) they use to do this. Here, we show that human neutrophils use trogocytosis, a previously undescribed neutrophil mode of microbial killing, to kill T . vaginalis . Trogocytosis is a process by which a cell takes “bites” of a neighboring cell, a process also referred to as “nibbling.” Using 3D and 4D live imaging, we show that neutrophils rapidly surround and trogocytose T . vaginalis , prior to parasite death. We rule out whole parasite engulfment (phagocytosis) and the employment of neutrophil extracellular traps (NETosis) in this rapid contact-dependent killing. We also show that antibody–fragment crystallizable (Fc) receptor interactions mediate neutrophil trogocytosis and killing and that serine proteases, commonly employed by neutrophils for microbial degradation, additionally play a role in parasite “nibbling”.