Trogocytosis: a novel mechanism neutrophils use to kill a large, motile extracellular parasite

Abstract

Trichomonas vaginalis (Tv), a human-infective parasite, causes the most common non-viral sexually transmitted infection worldwide and contributes to adverse inflammatory disorders. The immune response to Tv is poorly understood. Neutrophils (PMN) are the major immune cell present at the Tv-host interface and are thought to clear Tv. However, the mechanism of PMN clearance of Tv has not been characterized. We demonstrate that human PMN rapidly kill Tv in a dose dependent, contact-dependent and NET-independent manner. In contrast to phagocytosis, we observed that PMN killing of Tv involves taking “bites” of Tv 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, consistent with a model that opsonins mediate initial tight contact, but that serine protease activity is required for “nibbling.” Trogocytosis has previously been described as a way for immune cells to exchange membrane proteins, as a mechanism to spread intracellular bacteria from one cell to another and for E. histolytica to injure or kill host cells. Our analyses are the first to demonstrate the use of trogocytosis by a mammalian phagocyte for pathogen clearance and reveal a novel mechanism used by PMN to kill a large, highly motile target.