Parasite-induced Changes Research Articles

Parasitic Manipulation of Host Behaviour: Baculovirus SeMNPV EGT Facilitates Tree-Top Disease in Spodoptera exigua Larvae by Extending the Time to Death.

Many parasites enhance their dispersal and transmission by manipulating host behaviour. One intriguing example concerns baculoviruses that induce hyperactivity and tree-top disease (i.e., climbing to elevated positions prior to death) in their caterpillar hosts. Little is known about the underlying mechanisms of such parasite-induced behavioural changes. Here, we studied the role of the ecdysteroid UDP-glucosyltransferase (egt) gene of Spodoptera exigua multiple nucleopolyhedrovirus (SeMNPV) in tree-top disease in S. exigua larvae. Larvae infected with a mutant virus lacking the egt gene exhibited a shorter time to death and died before the induction of tree-top disease. Moreover, deletion of either the open reading frame or the ATG start codon of the egt gene prevented tree-top disease, indicating that the EGT protein is involved in this process. We hypothesize that SeMNPV EGT facilitates tree-top disease in S. exigua larvae by prolonging the larval time to death. Additionally, we discuss the role of egt in baculovirus-induced tree-top disease.

Lethal and nonlethal murine malarial infections differentially affect apoptosis, proliferation, and CD8 expression on thymic T cells.

Although thymic atrophy and apoptosis of the double-positive (DP) T cells have been reported in murine malaria, comparative studies investigating the effect of lethal and nonlethal Plasmodium infections on the thymus are lacking. We assessed the effects of P.yoelii lethal (17XL) and nonlethal (17XNL) infections on thymic T cells. Both strains affected the thymus. 17XL infection induced DP T-cell apoptosis and a selective decrease in surface CD8 expression on developing thymocytes. By contrast, more severe but reversible effects were observed during 17XNL infection. DP T cells underwent apoptosis, and proliferation of both DN and DP cells was affected around peak parasitemia. A transient increase in surface CD8 expression on thymic T cells was also observed. Adult thymic organ culture revealed that soluble serum factors, but not IFN-γ or TNF-α, contributed to the observed effects. Thus, lethal and nonlethal malarial infections led to multiple disparate effects on thymus. These parasite-induced thymic changes are expected to impact the naïve T-cell repertoire and the subsequent control of the immune response against the parasite. Further investigations are required to elucidate the mechanism responsible for these disparate effects, especially the reversible involution of the thymus in case of nonlethal infection.

Calling Behavior of Male Acheta domesticus Crickets Infected with Paragordius varius (Nematomorpha: Gordiida).

It is well established that parasites in the phylum Nematomorpha induce suicide behavior of their insect hosts to bring adult worms to the appropriate habitat for emergence. It is not well established, however, whether other nematomorph-induced behavioral alterations occur before worm emergence. The purpose of our study was to evaluate the effect of the nematomorph Paragordius varius on the calling behavior of the male house cricket Acheta domesticus . We hypothesized that cricket calling, an energetically expensive and risky behavior, would be a potential target for nematomorph-induced behavioral alterations. We assessed if and how infection with P. varius affects A. domesticus calling behavior and whether the presence of wings at time of exposure to P. varius influenced changes in calling behavior. We recorded the calling behavior of male A. domesticus over the course of their infection after exposure to P. various before or after wing development. Additionally, we assessed whether winged crickets were "callers" or "noncallers" before exposure. We found that regardless of cricket developmental stage (or age) at time of infection, infected crickets spent significantly less time calling than their uninfected counterparts but only during the later stages of infection. Developmental stage at infection did affect whether crickets became callers: when infected before wing development significantly more uninfected crickets initiated calling; there was no difference between infected and uninfected crickets when infected as winged adults. Infection was a factor in whether callers stopped calling, with more infected crickets ceasing to call than uninfected crickets. This is the first study to show that infection with nematomorphs affects calling behavior of their insect host. Cricket calling behavior is immensely complex and although it was difficult to elucidate the adaptive nature of these parasite-induced behavioral changes, this study lays the groundwork for future studies to begin teasing out the factors that will help make the determination between side effect of infection or parasite/host adaptation.

Identification of candidate mimicry proteins involved in parasite-driven phenotypic changes.

BackgroundEndoparasites with complex life cycles are faced with several biological challenges, as they need to occupy various ecological niches throughout their development. Host phenotypes that increase the parasite’s transmission rate to the next host have been extensively described, but few mechanistic explanations have been proposed to describe their proximate causes. In this study we explore the possibility that host phenotypic changes are triggered by the production of mimicry proteins from the parasite by using an ecological model system consisting of the infection of the threespine stickleback (Gasterosteus aculeatus) by the cestode Schistocephalus solidus.MethodUsing RNA-seq data, we assembled 9,093 protein-coding genes from which ORFs were predicted to generate a reference proteome. Based on a previously published method, we built two complementary analysis pipelines to i) establish a general classification of protein similarity among various species (pipeline A) and ii) identify candidate mimicry proteins showing specific host-parasite similarities (pipeline B), a key feature underlying the possibility of molecular mimicry.ResultsNinety-four tapeworm proteins showed high local sequence homology with stickleback proteins. Four of these candidates correspond to secreted or membrane proteins that could be produced by the parasite and eventually be released in or be in contact with the host to modulate physiological pathways involved in various phenotypes (e.g. behaviors). One of these candidates belongs to the Wnt family, a large group of signaling molecules involved in cell-to-cell interactions and various developmental pathways. The three other candidates are involved in ion transport and post-translational protein modifications. We further confirmed that these four candidates are expressed in three different developmental stages of the cestode by RT-PCR, including the stages found in the host.ConclusionIn this study, we identified mimicry candidate peptides from a behavior-altering cestode showing specific sequence similarity with host proteins. Despite their potential role in modulating host pathways that could lead to parasite-induced phenotypic changes and despite our confirmation that they are expressed in the developmental stage corresponding to the altered host behavior, further investigations will be needed to confirm their mechanistic role in the molecular cross-talk taking place between S. solidus and the threespine stickleback.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-015-0834-1) contains supplementary material, which is available to authorized users.

Digenean larvae--the cause and beneficiaries of the changes in host snails' thermal behavior.

Parasite-induced changes in host’s thermal preferences not only can be interpreted as a physiological defense response of the host but also can represent a pathological manifestation of the parasite. Both may become established in host-parasite relationships if they are beneficial for at least one of the counterparts. This study investigates parasite-induced changes in the thermoregulatory behavior of first intermediate hosts of Digenea (i.e. Lymnaea stagnalis and Planorbarius corneus), infected with Notocotylidae or Echinostomatidae larvae. The investigated parasite species developed different transmission strategies outside the body of a snail, which may imply a different effect on the behavior of their hosts. Notocotylus attenuatus in L. stagnalis and Notocotylus ephemera in P. corneus produce symptoms of anapyrexia, prolonging the lifespan of their hosts. By contrast, Echinoparyphium aconiatum in L. stagnalis and Echinostoma spiniferum in P. corneus interfere with defensive thermoregulatory behavior of host snails, causing their accelerated death. The results of laboratory research indicate that thermal preferences of the snails infected with all investigated trematodes facilitate the transmission of the parasites in environment.

Parasites that change predator or prey behaviour can have keystone effects on community composition

Parasites play pivotal roles in structuring communities, often via indirect interactions with non-host species. These effects can be density-mediated (through mortality) or trait-mediated (behavioural, physiological and developmental), and may be crucial to population interactions, including biological invasions. For instance, parasitism can alter intraguild predation (IGP) between native and invasive crustaceans, reversing invasion outcomes. Here, we use mathematical models to examine how parasite-induced trait changes influence the population dynamics of hosts that interact via IGP. We show that trait-mediated indirect interactions impart keystone effects, promoting or inhibiting host coexistence. Parasites can thus have strong ecological impacts, even if they have negligible virulence, underscoring the need to consider trait-mediated effects when predicting effects of parasites on community structure in general and biological invasions in particular.

Membrane transport in the malaria parasite and its host erythrocyte

As it grows and replicates within the erythrocytes of its host the malaria parasite takes up nutrients from the extracellular medium, exports metabolites and maintains a tight control over its internal ionic composition. These functions are achieved via membrane transport proteins, integral membrane proteins that mediate the passage of solutes across the various membranes that separate the biochemical machinery of the parasite from the extracellular environment. Proteins of this type play a key role in antimalarial drug resistance, as well as being candidate drug targets in their own right. This review provides an overview of recent work on the membrane transport biology of the malaria parasite-infected erythrocyte, encompassing both the parasite-induced changes in the membrane transport properties of the host erythrocyte and the cell physiology of the intracellular parasite itself.

Behavioral changes caused by Austrodiplostomum spp. in Hoplias malabaricus from the São Francisco River, Brazil

Traira (Hoplias malabaricus) is a neotropical fish that is widely distributed in freshwater environments in South America. In the present study, we documented the occurrence of metacercariae of Austrodiplostomum spp. (Diplostomidae) in the eyes and cranial cavity of H. malabaricus and described parasite-induced behavioral changes in the host. The fish were collected from the upper São Francisco River, in the Serra da Canastra mountain range, Minas Gerais, transported alive to the laboratory, observed for 2 weeks, and subsequently examined for parasites. Of the 35 fish examined, 28 (80 %) had free metacercariae in the vitreous humor (mean intensity=95.4; mean abundance=76.3), and 24 (68.57 %) had free metacercariae in the cranial cavity, mainly concentrated below the floor of the brain, at the height of the ophthalmic lobe (mean intensity=12.91; mean abundance=8.85). Specimens of H. malabaricus with a high intensity of infection in the brain displayed changes in swimming behavior.

Pathological Changes in Mermithid Nematode Infected Stictochironomus polystictus (Kieffer) (Diptera, Chironomidae, Chironominae)

Mermithid nematodes cause morphological and sexual anomalies in the pupae and adults of Stictochironomus polystictus (Kieffer). The parasite-induced changes resulted in the development of three types of intersexes. Structural alterations of adult males were variation of antennal length, appearance of antenna and number of flagellomeres, VIIIth abdominal segment, genitalia and associated appendages while in pupae, the length of antennal sheath and genital sac. However, the midge larvae infected with nematodes did not show any abnormality in morphological features. These entomopathogenic worms infecting male chironomids can feminize them and induce them to adopt a female behavior and return to water. So the worms apparently benefit from behavioral changes of the infected host, thereby reaching their abode where new hosts for its juveniles may be encountered. Since parasitized insects are usually castrated by worms before the beginning of the morphological changes, the behavioral alterations do not make additional fitness to the host.

Walking with insects: molecular mechanisms behind parasitic manipulation of host behaviour

Parasitic infections are often followed by changes in host behaviour. Numerous and exquisite examples of such behavioural alterations are known, covering a broad spectrum of parasites and hosts. Most descriptions of such parasite-induced changes in host behaviour are observational reports, while experimentally confirmed examples of parasite genes inducing these changes are limited. In this study, we review changes in invertebrate host behaviour observed upon infection by parasites and discuss such changes in an evolutionary context. We then explore possible mechanisms involved in parasite-induced changes in host behaviour. Genes and pathways known to play a role in invertebrate behaviour are reviewed, and we hypothesize how parasites (may) affect these pathways. This review provides the state of the art in this exciting, interdisciplinary field by exploring possible pathways triggered in hosts, suggesting methodologies to unravel the molecular mechanisms that lead to changes in host behaviour.

Phenolics-rich fraction of Khaya senegalensis stem bark: Antitrypanosomal activity and amelioration of some parasite-induced pathological changes

Context: The stem bark of Khaya senegalensis A. Juss (Meliaceae) is currently used for the treatment of trypanosomiasis by traditional practitioners in Nigeria.Objectives: The present study investigated the anti-Trypanosoma brucei brucei activity of phenolics-rich fraction of K. senegalensis (pfks) and its ameliorative effects on trypanosome-induced pathological changes.Materials and methods: The fraction was initially analyzed by gas chromatography-mass spectrometry (GC-MS). A 60 min time course experiment was conducted with various concentrations of the fraction using a 96-well microtiter plate technique and was further used to treat T. brucei infected rats at 100, 200 and 300 mg/kg body weight (BW). Indices of anemia as well as hepatic and renal functions were analyzed in all experimental animals at the end of the experiment.Results: The GC-MS analysis of the pfks revealed that the most abundant phytochemicals are phloroglucinol (40.56%) and 3,4-(dihydroxyphenyl) acetic acid (41.76%). The fraction showed a concentration dependent in vitro antitrypanosomal activity. Interestingly, the fraction completely eliminated the parasites from the bloodstream of infected rats without relapse during the experimental period at the dose of 300 mg/kg BW and also kept the parasites consistently lower at 100 and 200 mg/kg BW than that was recorded in the untreated infected rats. Furthermore, the severity of T. brucei-induced anemia and hepatic damage was significantly (p < 0.05) ameliorated in the 300 mg/kg BW treatment group whereas the parasite-induced renal damage was significantly (p < 0.05) ameliorated in all treatment groups.Conclusion: Data from this study may suggest that phenolics play an important role in the antitrypanosomal activity of K. senegalensis.

Modeling effective transmission pathways and control of the world’s most successful parasite

Toxoplasma gondii(T. gondii) is a single-celled, intracellular protozoan responsible for the disease toxoplasmosis. The parasite is prevalent worldwide, and it infects all warm-blooded vertebrates. Consumption of meats in which this parasite has encysted confers risk of infection to people and other animals, as does ingestion of water or foods contaminated with environmentally resistant oocysts excreted by cats. Vertical transmission (from mother to offspring) is also possible, leading to disease risk and contributing additional means of ensuring perpetuation of transmission. In this work, we adopt a differential equation model to investigate the effective transmission pathways of T. gondii, as well as potential control mechanisms. Detailed analyses are carried out to examine the significance of transmission routes, virulence, vertical transmission, parasite-induced changes in host behavior, and controls based on vaccination and harvesting. Modeling and analysis efforts may shed insights into understanding the complex life cycle of T. gondii.

Neural parasitology: how parasites manipulate host behaviour

The ability of parasites to alter the behaviour of their hosts fascinates both scientists and non-scientists alike. One reason that this topic resonates with so many is that it touches on core philosophical issues such as the existence of free will. If the mind is merely a machine, then it can be

Parasite-induced alterations of sensorimotor pathways in gammarids: collateral damage of neuroinflammation?

Some larval helminths alter the behavior of their intermediate hosts in ways that favor the predation of infected hosts, thus enhancing trophic transmission. Gammarids (Crustacea: Amphipoda) offer unique advantages for the study of the proximate factors mediating parasite-induced behavioral changes. Indeed, amphipods infected by distantly related worms (acanthocephalans, cestodes and trematodes) encysted in different microhabitats within their hosts (hemocoel, brain) present comparable, chronic, behavioral pathologies. In order to evaluate the potential connection between behavioral disturbances and immune responses in parasitized gammarids, this Review surveys the literature bearing on sensorimotor pathway dysfunctions in infected hosts, on the involvement of the neuromodulator serotonin in altered responses to environmental stimuli, and on systemic and neural innate immunity in arthropods. Hemocyte concentration and phenoloxidase activity associated with melanotic encapsulation are depressed in acanthocephalan-manipulated gammarids. However, other components of the arsenal deployed by crustaceans against pathogens have not yet been investigated in helminth-infected gammarids. Members of the Toll family of receptors, cytokines such as tumor necrosis factors (TNFs), and the free radical nitric oxide are all implicated in neuroimmune responses in crustaceans. Across animal phyla, these molecules and their neuroinflammatory signaling pathways are touted for their dual beneficial and deleterious properties. Thus, it is argued that neuroinflammation might mediate the biochemical events upstream of the serotonergic dysfunction observed in manipulated gammarids - a parsimonious hypothesis that could explain the common behavioral pathology induced by distantly related parasites, both hemocoelian and cerebral.

An overview of parasite-induced behavioral alterations – and some lessons from bats

An animal with a parasite is not likely to behave like a similar animal without that parasite. This is a simple enough concept, one that is now widely recognized as true, but if we move beyond that statement, the light that it casts on behavior fades quickly: the world of parasites, hosts and behavior is shadowy, and boundaries are ill-defined. For instance, at first glance, the growing list of altered behaviors tells us very little about how those alterations happen, much less how they evolved. Some cases of parasite-induced behavioral change are truly manipulative, with the parasite standing to benefit from the changed behavior. In other cases, the altered behavior has an almost curative, if not prophylactic, effect; in those cases, the host benefits. This paper will provide an overview of the conflicting (and coinciding) demands on parasite and host, using examples from a wide range of taxa and posing questions for the future. In particular, what does the larger world of animal behavior tell us about how to go about seeking insights - or at least, what not to do? By asking questions about the sensory-perceptual world of hosts, we can identify those associations that hold the greatest promise for neuroethological studies of parasite-induced behavioral alterations, and those studies can, in turn, help guide our understanding of how parasite-induced alterations evolved, and how they are maintained.

Parasite-induced behavioural changes to the trade-off between foraging and predator evasion in a marine snail

Trophic interactions in ecological communities not only affect consumer-resource densities, but also induce phenotypic responses that can ripple through a food web to influence prey resources, competitors and other predators (i.e. trait-mediated interactions). Predators affect short-term trade-off decisions in prey species through behavioural alterations, yet the role of parasites in the context of trait-mediated interactions is rarely discussed, despite our extensive knowledge of parasite-induced behavioural alterations. Adding parasites to the picture, the foraging–predation trade-off presents an interesting case where the effects of predator- and parasite-induced behavioural responses occur in conjunction. Empirical studies on the effect of parasites on trait-mediated anti-predator responses are still scarce, especially in marine systems. Our experiments used marine mud snails, Zeacumantus subcarinatus (Batillariidae), infected with the trematode parasites Maritrema novaezealandensis and Philophthalmus sp. to investigate the effects of trematode-induced behavioural alterations on the trade-off between food acquisition and predator avoidance in the presence of a range of predation cues. We found that the time taken to initiate anti-predator responses was overall significantly shorter in M. novaezealandensis-infected snails than in uninfected snails, while it was significantly longer for Philophthalmus-infected snails. In the simultaneous presence of odours from an injured conspecific and a crab predator, however, the reaction time between uninfected and M. novaezealandensis-infected snails did not differ while Philophthalmus-infected snails were still markedly slower than the former groups. Our results demonstrate species-specific parasite-induced behavioural changes in the presence of imminent predation risk. However, effects of the trematodes on overall feeding and fleeing times were not detected in our experiments; thus, the net effect of parasitism on the foraging–predation trade-off remains unknown.

Manipulative parasites may not alter intermediate host distribution but still enhance their transmission: field evidence for increased vulnerability to definitive hosts and non-host predator avoidance

Behavioural alterations induced by parasites in their intermediate hosts can spatially structure host populations, possibly resulting in enhanced trophic transmission to definitive hosts. However, such alterations may also increase intermediate host vulnerability to non-host predators. Parasite-induced behavioural alterations may thus vary between parasite species and depend on each parasite definitive host species. We studied the influence of infection with 2 acanthocephalan parasites (Echinorhynchus truttae and Polymorphus minutus) on the distribution of the amphipod Gammarus pulex in the field. Predator presence or absence and predator species, whether suitable definitive host or dead-end predator, had no effect on the micro-distribution of infected or uninfected G. pulex amphipods. Although neither parasite species seem to influence intermediate host distribution, E. truttae infected G. pulex were still significantly more vulnerable to predation by fish (Cottus gobio), the parasite's definitive hosts. In contrast, G. pulex infected with P. minutus, a bird acanthocephalan, did not suffer from increased predation by C. gobio, a predator unsuitable as host for P. minutus. These results suggest that effects of behavioural changes associated with parasite infections might not be detectable until intermediate hosts actually come in contact with predators. However, parasite-induced changes in host spatial distribution may still be adaptive if they drive hosts into areas of high transmission probabilities.

Cryptic biodiversity effects: importance of functional redundancy revealed through addition of food web complexity

Interactions between predators and the degree of functional redundancy among multiple predator species may determine whether herbivores experience increased or decreased predation risk. Specialist parasites can modify predator behavior, yet rarely have cascading effects on multiple predator species and prey been evaluated. We examined influences of specialist phorid parasites (Pseudacteon spp.) on three predatory ant species and herbivores in a coffee agroecosystem. Specifically, we examined whether changes in ant richness affected fruit damage by the coffee berry borer (Hypothenemus hampei) and whether phorids altered multi-predator effects. Each ant species reduced borer damage, and without phorids, increasing predator richness did not further decrease borer damage. However, with phorids, activity of one ant species was reduced, indicating that the presence of multiple ant species was necessary to limit borer damage. In addition, phorid presence revealed synergistic effects of multiple ant species, not observed without the presence of this parasite. Thus, a trait-mediated cascade resulting from a parasite-induced predator behavioral change revealed the importance of functional redundancy, predator diversity, and food web complexity for control of this important pest.

Modifications in erythrocyte membrane zeta potential by Plasmodium falciparum infection

The zeta potential (ZP) is an electrochemical property of cell surfaces that is determined by the net electrical charge of molecules exposed at the surface of cell membranes. Membrane proteins contribute to the total net electrical charge of cell surfaces and can alter ZP through variation in their copy number and changes in their intermolecular interactions. Plasmodium falciparum extensively remodels its host red blood cell (RBC) membrane by placing ‘knob’-like structures at the cell surface. Using an electrophoretic mobility assay, we found that the mean ZP of human RBCs was −15.7mV. In RBCs infected with P. falciparum trophozoites (‘iRBCs’), the mean ZP was significantly lower (−14.6mV, p<0.001). Removal of sialic acid from the cell surface by neuraminidase treatment significantly decreased the ZP of both RBCs (−6.06mV) and iRBCs (−4.64mV). Parasite-induced changes in ZP varied by P. falciparum clone and the presence of knobs on the iRBC surface. Variations in ZP values were accompanied by altered binding of iRBCs to human microvascular endothelial cells (MVECs). These data suggest that parasite-derived knob proteins contribute to the ZP of iRBCs, and that electrostatic and hydrophobic interactions between iRBC and MVEC membranes are involved in cytoadherence.

Human erythrocyte remodelling during Plasmodium falciparum malaria parasite growth and egress

The intra-erythrocyte growth and survival of the malarial parasite Plasmodium falciparum is responsible for both uncomplicated and severe malaria cases and depends on the parasite's ability to remodel its host cell. Host cell remodelling has several functions for the parasite, such as acquiring nutrients from the extracellular milieu because of the loss of membrane transporters upon erythrocyte differentiation, avoiding splenic clearance by conferring cytoadhesive properties to the infected erythrocyte, escaping the host immune response by exporting antigenically variant proteins at the red blood cell surface. In addition, parasite-induced changes at the red blood cell membrane and sub-membrane skeleton are also necessary for the efficient release of the parasite progeny from the host cell. Here we review these cellular and molecular changes, which might not only sustain parasite growth but also prepare, at a very early stage, the last step of egress from the host cell.