Abstract
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.
Highlights
Trichomonas vaginalis is a unicellular, flagellated eukaryote that lives as an obligate extracellular parasite, restricted to humans [1,2,3]
Trogocytosis is a process by which a cell takes “bites” of a neighboring cell, a process 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 and the employment of neutrophil extracellular traps (NETosis) in this rapid contact-dependent killing
Summary
Trichomonas vaginalis is a unicellular, flagellated eukaryote that lives as an obligate extracellular parasite, restricted to humans [1,2,3]. The World Health Organization reports approximately 275 million cases each year [1,4]. In the United States, an estimated 1.1 million new infections occur every year [5]. T. vaginalis infection is associated with increased transmission of and susceptibility to HIV, as well as increased progression of cervical cancer in human papilloma virus (HPV)+ individuals [11,12,13,14,15,16,17]. T. vaginalis was recently classified as a neglected parasitic infection [5] because it disproportionately affects underserved communities [5,18] and contributes to reproductive health disparities; trichomoniasis is linked to pelvic inflammatory disorder, premature and underweight infant birth, infertility, and endometriosis [5,11]
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