Changes In Host Behaviour Research Articles

Lyssavirus M protein degrades neuronal microtubules by reprogramming mitochondrial metabolism.

Infection with neurotropic viruses may result in changes in host behavior, which are closely associated with degenerative changes in neurons. The lyssavirus genus comprises highly neurotropic viruses, including the rabies virus (RABV), which has been shown to induce degenerative changes in neurons, marked by the self-destruction of axons. The underlying mechanism by which the RABV degrades neuronal cytoskeletal proteins remains incomplete. In this study, we show that infection with RABV or overexpression of its M protein can disrupt mitochondrial metabolism by binding to Slc25a4. This leads to a reduction in NAD+ production and a subsequent influx of Ca2+ from the endoplasmic reticulum and mitochondria into the cytoplasm of neuronal cell lines, activating Ca2+-dependent proteinase calpains that degrade α-tubulin. We further screened the M proteins of different lyssaviruses and discovered that the M protein of the dog-derived RABV strain (DRV) does not degrade α-tubulin. Sequence analysis of the DRV M protein and that of the lab-attenuated RABV strain CVS revealed that the 57th amino acid is vital for M-induced microtubule degradation. We generated a recombinant RABV with a mutation at the 57th amino acid position in its M protein and showed that this mutation reduces α-tubulin degradation in vitro and axonal degeneration in vivo. This study elucidates the mechanism by which lyssavirus induces neuron degeneration.IMPORTANCEPrevious studies have suggested that RABV (rabies virus, the representative of lyssavirus) infection induces structural abnormalities in neurons. But there are few articles on the mechanism of lyssavirus' effect on neurons, and the mechanism of how RABV infection induces neurological dysfunction remains incomplete. The M protein of lyssavirus can downregulate cellular ATP levels by interacting with Slc25a4, and this decrease in ATP leads to a decrease in the level of NAD+ in the cytosol, which results in the release of Ca2+ from the intracellular calcium pool, the endoplasmic reticulum, and mitochondria. The presence of large amounts of Ca2+ in the cytoplasm activates Ca2+-dependent proteases and degrades microtubule proteins. The amino acid 57 of M protein is the key site determining its disruption of mitochondrial metabolism and subsequent neuron degeneration.

Turnover of strain-level diversity modulates functional traits in the honeybee gut microbiome between nurses and foragers

BackgroundStrain-level diversity is widespread among bacterial species and can expand the functional potential of natural microbial communities. However, to what extent communities undergo consistent shifts in strain composition in response to environmental/host changes is less well understood.ResultsHere, we used shotgun metagenomics to compare the gut microbiota of two behavioral states of the Western honeybee (Apis mellifera), namely nurse and forager bees. While their gut microbiota is composed of the same bacterial species, we detect consistent changes in strain-level composition between nurses and foragers. Single nucleotide variant profiles of predominant bacterial species cluster by behavioral state. Moreover, we identify strain-specific gene content related to nutrient utilization, vitamin biosynthesis, and cell–cell interactions specifically associated with the two behavioral states.ConclusionsOur findings show that strain-level diversity in host-associated communities can undergo consistent changes in response to host behavioral changes modulating the functional potential of the community.

Responding to infection affects more than just the host

An infection triggers a dramatic suite of changes in host physiology and behavior. While seemingly localized, the host response affects many other organisms, both within and beyond the boundaries of the host’s body, with far-reaching ecological implications. Here, I call for more awareness and integration of those potential ‘off-host’ effects.

Exploring COVID-19 Adaptation Strategies in Nepalese Tourism Industry: A Qualitative Study

The tourism industry is a major part of the global economy but is also affected by crises and disasters. The COVID-19 pandemic has presented challenges for tourism and hospitality business owners in maintaining sustainability while also keeping employees safe. Despite studies on how to manage uncertainty, there is a lack of concrete examples and research on actual practices used by businesses in this sector, particularly in Nepal. This research identifies and explores the adaptations made by hospitality business owners to maintain continuity and employee safety during this uncertain time. This research, using a qualitative approach and semi-structured interviews in a conversational style with five tourism business owners in Pokhara, explores the adaptations made by these businesses to maintain continuity and employee safety during a crisis and pandemic. The paper analysed data collected from interviews through thematic analysis and used pseudonyms to protect participant anonymity. Four key adaptation strategies were identified: human resource management, reorganising operations, managing health aspects and implementing specific crisis management measures. The findings revealed that businesses were able to explore new opportunities, invest in technology, and improve efficiency. They also provided training and monitoring for sanitation and hygiene, and adapted to changes in guest and host behaviour. The paper highlights the efforts these business owners made to adapt and sustain their businesses during a difficult time.

Wolbachia-Driven Memory Loss in a Parasitic Wasp Increases Superparasitism to Enhance Horizontal Transmission.

Horizontal transmission of the endosymbiont, Wolbachia, may occur during superparasitism when parasitoid females deposit a second clutch of eggs on a host. Wolbachia may increase the superparasitism tendency of Trichogramma wasps by depriving their memory. To test this hypothesis, we investigated the effects of conditioning experience and memory inhibitors (actinomycin D [ACD] and anisomycin [ANI]) on memory capacity, and expressions of memory-related genes (CREB1 and PKA), and superparasitism frequency of Wolbachia-infected (TDW) and uninfected (TD) lines of Trichogramma dendrolimi after conditioning with lemon or peppermint odor. We detected the presence of Wolbachia in eggs, larvae, pre-pupae, pupae, and adults of Trichogramma by using fluorescence in situ hybridization. The results showed that TDW females had a more reduced memory capacity than TD females after conditioning. Compared with TD females, TDW females showed a higher proportion of superparasitism and a downregulation of CREB1 and PKA genes after conditioning. TD females fed ACD or ANI showed a higher tendency for superparasitism and a downregulation of CREB1 and PKA, along with memory loss after conditioning than TD females fed honey solution only. The presence of Wolbachia was detected in the anterior region of the larva, pre-pupa, and pupa, but was not found in the head of the adult. The results provide evidence of host behavioral manipulation of Wolbachia by depriving memory of host Trichogramma wasps based on Poulin' s criteria. These host behavioral changes led by Wolbachia may be caused by the virulence of Wolbachia on the nervous system of the host. IMPORTANCE The endosymbiotic bacteria, Wolbachia, live widely within cells of arthropods. Wolbachia are not only transmitted vertically from host mother to offspring, but are also transmitted horizontally among host individuals. Horizontal transmission is expected to occur during superparasitism when host parasitoid females deposit a clutch of eggs on a host previously parasitized by the same parasitoid species. Thus, a question is proposed regarding whether superparasitism behavior is a behavior modification induced by the symbiont to favor symbiont transmission. This study highlights behavioral mechanisms of Wolbachia-induced superparasitism in Trichogramma wasps and the manipulation of symbionts on host parasitoids.

Infection increases activity via Toll dependent and independent mechanisms in Drosophila melanogaster.

Host behavioural changes are among the most apparent effects of infection. 'Sickness behaviour' can involve a variety of symptoms, including anorexia, depression, and changed activity levels. Here, using a real-time tracking and behavioural profiling platform, we show that in Drosophila melanogaster, several systemic bacterial infections cause significant increases in physical activity, and that the extent of this activity increase is a predictor of survival time in some lethal infections. Using multiple bacteria and D. melanogaster immune and activity mutants, we show that increased activity is driven by at least two different mechanisms. Increased activity after infection with Micrococcus luteus, a Gram-positive bacterium rapidly cleared by the immune response, strictly requires the Toll ligand spätzle. In contrast, increased activity after infection with Francisella novicida, a Gram-negative bacterium that cannot be cleared by the immune response, is entirely independent of both Toll and the parallel IMD pathway. The existence of multiple signalling mechanisms by which bacterial infections drive increases in physical activity implies that this effect may be an important aspect of the host response.

Dividing up the bill: Interactions between how parasitoids manipulate host behaviour and who pays the cost

Abstract Controlling host behaviour can be costly for parasites. In some parasitic systems, such as insect parasitoids, this physiological cost can be paid for by the mother parasite, her offspring or both. Parasitoid wasps provide examples of how individual parasites in a host–parasite system can vary in their opportunity, means and motive (i.e. fitness benefits) for manipulating host behaviour. Changes in host behaviour that occur very soon after infection are typically paid for by the mother parasitoid. She has the greatest opportunity (offspring are often still eggs), the means (neuroactive venoms) and benefits by promoting her offspring's success. Changes in host behaviour that occur late in the development of the offspring (e.g. host bodyguard behaviour) often hinge on some behaviour of the offspring (e.g. the exiting of the host). In these cases, the cost is paid largely by the offspring. The offspring have the greater opportunity, the means (e.g. secreting compounds into the host) and directly benefit by their increased survival. Gene delivery agents, such as symbiotic viruses, allow a reduction in the direct cost of parasitic manipulation to the parasite because the host is induced to use its own resources to produce the compounds needed to alter its behaviour. However, this method leads to indirect costs that are paid for by the offspring, due to a reduction in the host's resources that are available for their own growth. In gregarious systems, the possibility of cheating among the offspring (i.e. some individuals paying less than others to alter host behaviour) may select for modes of control that make cheating difficult. Determining who pays the physiological cost of manipulating host behaviour, and why, promises exciting insights into the evolution of parasitic manipulation in these systems. Read the free Plain Language Summary for this article on the Journal blog.

Intraspecific Genetic Variation of Anisakis typica in Indian Mackerel Caught from the Gulf of Thailand, Samut Songkhram Province.

Anisakis nematodes infecting Indian mackerel (Rastrelliger kanagurta) were initially discovered in Thailand in our preliminary investigation. Nevertheless, the species of Anisakis collected has not been determined nor has its genetic variation been researched. Thus, this study aimed to molecularly identify the species of Anisakis specimens using the internal transcribed spacer (ITS) region of ribosomal DNA sequences. In addition, the intraspecific genetic variation was also determined using mitochondrial cytochrome oxidase subunit II (COII) gene sequences. The phylogenetic relationships of the ITS region classified all samples into Anisakis typica; however, the genetic variation between them could not be distinguished. By contrast, the phylogenetic tree analysis of the COII region identified all samples as A. typica, with 17 different haplotypes by 66 polymorphic sites and five of the substitutions resulted in amino acid change. Additionally, the distribution pattern of the COII region can be separated into two groups between South America and Asian countries. All our haplotypes belong to Asian countries. Compared with the two genetic markers used in this investigation, COII appears to be a better candidate for studying genetic variation sensitive to environmental changes and intermediate or definitive host behavioral changes.

Shift and homogenization of gut microbiome during invasion in marine fishes

Biological invasion is one of the main components of global changes in aquatic ecosystems. Unraveling how establishment in novel environments affects key biological features of animals is a key step towards understanding invasion. Gut microbiome of herbivorous animals is important for host health but has been scarcely assessed in invasive species. Here, we characterized the gut microbiome of two invasive marine herbivorous fishes (Siganus rivulatus and Siganus luridus) in their native (Red Sea) and invaded (Mediterranean Sea) ranges. The taxonomic and phylogenetic diversity of the microbiome increased as the fishes move away from the native range and its structure became increasingly different from the native microbiome. These shifts resulted in homogenization of the microbiome in the invaded range, within and between the two species. The shift in microbial diversity was associated with changes in its functions related with the metabolism of short-chain fatty acids. Altogether, our results suggest that the environmental conditions encountered by Siganidae during their expansion in Mediterranean ecosystems strongly modifies the composition of their gut microbiome along with its putative functions. Further studies should pursue to identify the precise determinants of these modifications (e.g. changes in host diet or behavior, genetic differentiation) and whether they participate in the ecological success of these species.

Distinct Cecal and Fecal Microbiome Responses to Stress Are Accompanied by Sex- and Diet-Dependent Changes in Behavior and Gut Serotonin.

Although diet- and stress-induced perturbations in the microbiome (biotic and abiotic factors) associate with changes in host behavior via the microbiota-gut-brain axis, few mechanisms have been identified. The identification of causative pathways by which the microbiome influences host behavior therefore would benefit from the application of evidence-based conceptual frameworks. One such causal framework is microbial endocrinology which is the study of neuroendocrine axes as avenues of bi-directional neurochemical-based host-microbe crosstalk. As such, we investigated the relationship between diet- and stress-induced alterations in behavior, regional gut serotonergic response, and concomitant changes in the cecal and fecal bacterial populations of male and female mice. Our results demonstrate that sex is a dominant factor in determining compositional changes in the gut microbiome in response to stress and diet modifications. Intestinal serotonergic responses to stress were observed in both sexes but dietary modifications uniquely affected region-specific changes in males and females. Likewise, behavioral alterations diverged between male and female mice. Together, these results demonstrate distinct sex-dependent relationships between cecal and fecal bacterial taxa and behavioral- and serotonergic-responses to stress and diet. The present study demonstrates the importance of including both male and female sexes in the examination of the microbiota-gut-brain axis. As different microbial taxa were identified to associate with the behavioral and gut serotonergic responses of male and female mice, certain bacterial species may hold sex-dependent functional relevance for the host. Future investigations seeking to develop microbiome-based strategies to afford host stress resilience should include sex-based differences in the microbiome.

SPARSEMODr: Rapidly simulate spatially explicit and stochastic models of COVID-19 and other infectious diseases.

Building realistically complex models of infectious disease transmission that are relevant for informing public health is conceptually challenging and requires knowledge of coding architecture that can implement key modeling conventions. For example, many of the models built to understand COVID-19 dynamics have included stochasticity, transmission dynamics that change throughout the epidemic due to changes in host behavior or public health interventions, and spatial structures that account for important spatio-temporal heterogeneities. Here we introduce an R package, SPARSEMODr, that allows users to simulate disease models that are stochastic and spatially explicit, including a model for COVID-19 that was useful in the early phases of the epidemic. SPARSEMOD stands for SPAtial Resolution-SEnsitive Models of Outbreak Dynamics, and our goal is to demonstrate particular conventions for rapidly simulating the dynamics of more complex, spatial models of infectious disease. In this report, we outline the features and workflows of our software package that allow for user-customized simulations. We believe the example models provided in our package will be useful in educational settings, as the coding conventions are adaptable, and will help new modelers to better understand important assumptions that were built into sophisticated COVID-19 models.

Toxoplasmosis: Targeting neurotransmitter systems in psychiatric disorders.

The most common form of the disease caused by Toxoplasma gondii (T. gondii)is latent toxoplasmosis due to the formation of tissue cysts in various organs, such as the brain. Latent toxoplasmosis is probably a risk factor in the development of some neuropsychiatric disorders. Behavioral changes after infection are caused by the host immune response, manipulation by the parasite, central nervous system (CNS) inflammation, as well as changes in hormonal and neuromodulator relationships. The present review focused on the exact mechanisms of T. gondii effect on the alteration of behavior and neurotransmitter levels, their catabolites and metabolites, as well as the interaction between immune responses and this parasite in the etiopathogenesis of psychiatric disorders. The dysfunction of neurotransmitters in the neural transmission is associated with several neuropsychiatric disorders. However, further intensive studies are required to determine the effect of this parasite on altering the level of neurotransmitters and the role of neurotransmitters in the etiology of host behavioral changes.

Potential linkage between Toxoplasma gondii infection and physical education scores of college students.

ObjectiveToxoplasma gondii is a worldwide protozoan parasite that could infect virtually all warm-blooded animals, including humans. Our study aimed to investigate the prevalence of T. gondii infection in college students at Anhui province, China and to assess risk factors for T. gondii infection in college students. Moreover, growing studies demonstrated the association between T. gondii infection and host behavioral changes. We also studied the linkage between T. gondii and physical education (PE) scores of college students.MethodsA total of 2704 serum samples of medical school students attending physical education lessons were collected from September 2017 to September 2019 and evaluated for T. gondii IgG antibodies using an enzyme-linked immunosorbent assay (ELISA). Questionnaires and statistical analysis were used to determine the risk factors for T. gondii infection. We also analysed PE scores of T. gondii -infected students and T. gondii-uninfected students.ResultsThe overall seroprevalence of T. gondii was 11.5%. The main risk factors related to T. gondii infection in college students were cat in the household and gardening or agriculture activity. Furthermore, in the basketball group and the soccer group, scores of T. gondii seropositive students were significantly higher than those of seronegative students, while in other sports there was no difference between scores of T. gondii-infected students and T. gondii uninfected students.ConclusionThis is the first report of T. gondii seroprevalence in college students in Anhui province, China.

Vancomycin-Induced Changes in Host Immunity and Behavior: Comparative Genomic and Metagenomic Analysis in C57BL/6 and BALB/c Mice.

The consequence of treatment with antibiotics on the gut microbiota can be destructive. The antibiotics, however, can be utilized to understand the role of gut microbiota on the host physiology. Earlier, we reported the efficacy of vancomycin in gut microbiota perturbation. We continued to understand the effect of restoration kinetics of perturbed gut microbiota on the immunity and behavior of Th1 (C57BL/6)- and Th2 (BALB/c)-biased mice. We studied restoration kinetics of the gut microbiota for two months following the withdrawal of vancomycin treatment in both mice strains. We analyzed cecal microbiome composition, different behavioral assays, and expression of select genes associated with stress and barrier function in gut and brain. Metagenomic analysis of gut microbiota revealed that the treatment with vancomycin caused a significant decrease in the relative abundance of Firmicutes and Bacteroidetes phyla with a time-dependent increase in Proteobacteria and Verrucomicrobia phyla. Maximum restoration (> 70%) of gut microbiota happened by the 15th day of withdrawal of vancomycin. BALB/c mice showed a more efficient restoration of gut microbiota compared to C57BL/6 mice. We established the correlation patterns of gut microbiota alteration and its effect on (a) the behavior of mice, (b) expression of key brain molecules, and (c) immunity-related genes. The results revealed that the gut microbiome profiling, behavior, and immune responses varied significantly between Th1- and Th2-biased mice. By withdrawing the treatment with vancomycin of major gut microbes, important physiological and behavioral changes of both mice strains returned to the normal (untreated control) level.

Mussel Shutdown: Does the Fear of Trematodes Regulate the Functioning of Filter Feeders in Coastal Ecosystems?

Parasite infections have negative impacts on their hosts. Accordingly, many organisms try to detect and avoid infective parasite stages, leading to changes in host behaviour or physiology. Such non-consumptive effects on host traits can have cascading impacts on whole ecosystems but remain largely overlooked. Here, we discuss the potential impacts of the presence of free-living trematode stages on blue mussels Mytilus edulis, an important ecosystem engineer in coastal habitats, and highlight the ecological implications of these interactions. Specifically, we discuss how parasite avoidance behaviour can regulate the filtration activity of these bivalves in coastal ecosystems and show how even moderate changes in mussel behaviour can lead to far-reaching shifts in energy flow. Such processes might be further amplified under future climate change developments, since both parasite abundance and biotic productivity are highly temperature dependent. Overall, we hypothesize that, in addition to their more evident consumptive impacts, trematodes act as cryptic ecosystem engineers by shaping bivalve filtration processes via non-consumptive effects. Due to our still very limited understanding of these parasite-mediated processes, we outline key questions for future research directions. We hope this perspective will help encourage new efforts to empirically investigate these fascinating processes that can be crucial regulatory forces in complex ecological systems.

CD8 T cells drive anorexia, dysbiosis, and blooms of a commensal with immunosuppressive potential after viral infection

Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.

Prophylactic host behaviour discourages pathogen exploitation

Much work has considered the evolution of pathogens, but little is known about how they respond to changes in host behaviour. We build a model of sublethal disease effects where hosts are able to choose to engage in prophylactic measures that reduce the likelihood of disease transmission. This choice is mediated by utility costs and benefits associated with prophylaxis, and the fraction of hosts engaged in prophylaxis is also affected by population dynamics. When prophylactic host behaviour occurs, we find that the level of pathogen host exploitation is reduced, by the action of selection, relative to the level that would otherwise be predicted in the absence of prophylaxis. Our work emphasizes the significance of the transmission-recovery trade-off faced by the pathogen and the ability of the pathogen to influence host prophylactic behaviour.

Parasite-modified behaviour in non-trophic transmission: trematode parasitism increases the attraction between snail intermediate hosts

Many parasites with complex life cycles cause host behavioural changes that increase the likelihood of transmission to the next host. Parasite modification is often found in trophic transmission, but its influence on non-trophic transmission is unclear. In trematodes, transmission from the first to second intermediate host is non-trophic, suggesting that free-swimming larvae (cercariae) emerging in closer proximity to the next host would have higher transmission success. We performed a series of behavioural experiments with echinostome trematodes and their snail hosts to determine if potential second hosts (ramshorn snail, genus Planorbella Haldeman, 1842) were more attracted to parasitized first hosts (marsh pondsnail, Lymnaea elodes Say, 1821). In a Y maze, a responding snail (Planorbella sp.) was placed in the base and its response to five treatments was assessed: no stimulus, turion duckweed (Lemna turionifera Landolt; a food item), non-parasitized L. elodes, parasitized L. elodes, and finally parasitized versus non-parasitized L. elodes. Snails showed some attraction to uninfected snails, but had a stronger response to infected first host snails. These results indicate that potential second host snails were more attracted to parasitized, heterospecific first host snails over non-parasitized heterospecific snails. This study demonstrates that echinostome trematodes alter snail behaviour by changing navigational choices in uninfected potential hosts through a chemical communication mechanism.

Spatiotemporal heterogeneity decouples infection parameters of amphibian chytridiomycosis.

Emerging infectious diseases are responsible for declines in wildlife populations around the globe. Mass mortality events associated with emerging infectious diseases are often associated with high number of infected individuals (prevalence) and high pathogen loads within individuals (intensity). At the landscape scale, spatial and temporal variation in environmental conditions can alter the relationship between these infection parameters and blur the overall picture of disease dynamics. Quantitative estimates of how infection parameters covary with environmental heterogeneity at the landscape scale are scarce. If we are to identify wild populations at risk of disease epidemics, we must elucidate the factorsthat shape, and potentially decouple, the link between pathogen prevalence and intensity of infection over complex ecological landscapes. Using a network of 41 populations of the amphibian host Rana pipiens in Ontario, Canada, we present the spatial and temporal heterogeneity in pathogen prevalence and intensity of infection of the chytrid fungus Batrachochytrium dendrobatidis (Bd), across a 3-year period. We then quantify how covariation between both infection parameters measured during late summer is modified by previously experienced spatiotemporal environmental heterogeneity across 14 repeat sampled populations. Late summer Bd infection parameters are governed, at least in part, by different environmental factors operating during separate host life-history events. Our results provide evidence for a relationship between Bd prevalence and thermal regimes prior to host breeding at the site level, and a relationship between intensity of infection and aquatic conditions (precipitation, hydroshed size and river density) throughout host breeding period at the site level. This demonstrates that microclimatic variation within temporal windows can drive divergent patterns of pathogen dynamics within and across years, by effecting changes in host behaviour which interfere with the pathogen's ability to infect and re-infect hosts. A clearer understanding of the role that spatiotemporal heterogeneity has upon infection parameters will provide valuable insights into host-pathogen epidemiology, as well as more fundamental aspects of the ecology and evolution of interspecific interactions.

High-Resolution Infection Kinetics of Entomopathogenic Nematodes Entering Drosophila melanogaster

Entomopathogenic nematodes (EPNs) have been a useful model for studying wound healing in insects due to their natural mechanism of entering an insect host either through the cuticle or an orifice. While many experiments have shed light on nematode and host behavior, as well as the host immune response, details regarding early nematode entry and proliferative events have been limited. Using high-resolution microscopy, we provide data on the early infection kinetics of Heterorhabditis bacteriophora and its symbiotic bacteria, Photorhabdus luminescens. EPNs appendage themselves to the host and enter through the host cuticle with a drill-like mechanism while leaving their outer sheath behind. EPNs immediately release their symbiotic bacteria in the host which leads to changes in host behavior and septicemia within 6 h while EPNs travel through the host in a predictable manner, congregating in the anterior end of the host. This paper sheds light on the entry and proliferative events of EPN infection, which will further aid in our understanding of wound healing and host immune activation at a high spatiotemporal resolution.