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.

Approximately 800 million people worldwide are infected with one or more species of skin-penetrating nematodes. These parasites persist in the environment as developmentally arrested third-stage infective larvae (iL3s) that navigate toward host-emitted cues, contact host skin, and penetrate the skin. iL3s then reinitiate development inside the host in response to sensory cues, a process called activation. Here, we investigate how chemosensation drives host seeking and activation in skin-penetrating nematodes. We show that the olfactory preferences of iL3s are categorically different from those of free-living adults, which may restrict host seeking to iL3s. The human-parasitic threadworm Strongyloides stercoralis and hookworm Ancylostoma ceylanicum have highly dissimilar olfactory preferences, suggesting that these two species may use distinct strategies to target humans. CRISPR/Cas9-mediated mutagenesis of the S. stercoralis tax-4 gene abolishes iL3 attraction to a host-emitted odorant and prevents activation. Our results suggest an important role for chemosensation in iL3 host seeking and infectivity and provide insight into the molecular mechanisms that underlie these processes.

Background Skin-penetrating nematodes of the genus Strongyloides infect over 600 million people, posing a major global health burden. Their life cycle includes both a parasitic and free-living generation. During the parasitic generation, infective third-stage larvae (iL3s) actively engage in host seeking. During the free-living generation, the nematodes develop and reproduce on host feces. At different points during their life cycle, Strongyloides species encounter a wide variety of host-associated and environmental bacteria. However, the microbiome associated with Strongyloides species, and the behavioral and physiological interactions between Strongyloides species and bacteria, remain unclear. Results We first investigated the microbiome of the human parasite Strongyloides stercoralis using 16S-based amplicon sequencing. We found that S. stercoralis free-living adults have an associated microbiome consisting of specific fecal bacteria. We then investigated the behavioral responses of S. stercoralis and the closely related rat parasite Strongyloides ratti to an ecologically diverse panel of bacteria. We found that S. stercoralis and S. ratti showed similar responses to bacteria. The responses of both nematodes to bacteria varied dramatically across life stages: free-living adults were strongly attracted to most of the bacteria tested, while iL3s were attracted specifically to a narrow range of environmental bacteria. The behavioral responses to bacteria were dynamic, consisting of distinct short- and long-term behaviors. Finally, a comparison of the growth and reproduction of S. stercoralis free-living adults on different bacteria revealed that the bacterium Proteus mirabilis inhibits S. stercoralis egg hatching, and thereby greatly decreases parasite viability. Conclusions Skin-penetrating nematodes encounter bacteria from various ecological niches throughout their life cycle. Our results demonstrate that bacteria function as key chemosensory cues for directing parasite movement in a life-stage-specific manner. Some bacterial genera may form essential associations with the nematodes, while others are detrimental and serve as a potential source of novel nematicides.

A variety of anthropogenic threats cause mortality and population declines of procellariiform seabirds. Globally, fledglings of many colonial procellariiforms become stranded in towns and cities during their first flights from the nest, which occur at night. Since the 1960s, when the phenomenon became widely known, these strandings have been largely attributed to attraction toward artificial lights at night (ALAN). Artificial light attraction has been blamed due to the predictable, annual nature of strandings; the large numbers of birds found in lighted areas during stranding events; and the inexperience of fledglings in interpreting sensory stimuli. However, up‐to‐date, few alternative hypotheses to that of light attraction have been suggested, and few if any have been explored experimentally. In this paper, we do not seek to refute the light attraction hypothesis. Instead, our objectives are threefold. We wish to (1) highlight the current evidence for light attraction in procellariiforms; (2) identify where evidence may be lacking or subject to confirmation bias; and (3) suggest alternative hypotheses and possible experimental approaches to study them. Given the imperiled nature of many of the affected species and the need to explore and address this source of mortality, our goal in this review is to accelerate and diversify research efforts on this topic.

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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.