Strong density-dependent competition and acquired immunity constrain parasite establishment: implications for parasite aggregation

The vast majority of parasites exhibit an aggregated frequency distribution within their host population, such that most hosts have few or no parasites while only a minority of hosts are heavily infected. One exception to this rule is the trophically transmitted parasite Pterygodermatites peromysci of the white-footed mouse (Peromyscus leucopus), which is randomly distributed within its host population. Here, we ask: what are the factors generating the random distribution of parasites in this system when the majority of macroparasites exhibit non-random patterns? We hypothesise that tight density-dependent processes constrain parasite establishment and survival, preventing the build-up of parasites within individual hosts, and preclude aggregation within the host population. We first conducted primary infections in a laboratory experiment using white-footed mice to test for density-dependent parasite establishment and survival of adult worms. Secondary or challenge infection experiments were then conducted to investigate underlying mechanisms, including intra-specific competition and host-mediated restrictions (i.e. acquired immunity). The results of our experimental infections show a dose-dependent constraint on within-host-parasite establishment, such that the proportion of mice infected rose initially with exposure, and then dropped off at the highest dose. Additional evidence of density-dependent competition comes from the decrease in worm length with increasing levels of exposure. In the challenge infection experiment, previous exposure to parasites resulted in a lower prevalence and intensity of infection compared with primary infection of naïve mice; the magnitude of this effect was also density-dependent. Host immune response (IgG levels) increased with the level of exposure, but decreased with the number of worms established. Our results suggest that strong intra-specific competition and acquired host immunity operate in a density-dependent manner to constrain parasite establishment, driving down aggregation and ultimately accounting for the observed random distribution of parasites.     

Targeting tumors with LIGHT to generate metastasis-clearing immunity

Metastatic diseases cause the majority of morbidity and mortality of cancer patients. Established tumors form both physical and immunological barriers to limit immune detection and destruction. Current immunotherapy of vaccination and adoptive transfer shows limited effect at least in part due to the existing barriers in the tumors and depending on the knowledge of tumor antigens. Tumor necrosis factor (TNF) superfamily (TNFSF) member 14 (TNFSF14) LIGHT interacts with stromal cells, dendritic cells (DCs), NK cells, na?ve and activated T cells and tumor cells inside the tumor tissues via its two functional receptors, HVEM and lymphotoxin beta receptor (LTbetaR). Targeting tumor tissues with LIGHT leads to augmentation of priming, recruitment, and retention of effector cells at tumor sites, directly or indirectly, to induce strong anti-tumor immunity to inhibit the growth of primary tumors as well as eradicate metastases. Intratumor treatment would break tumor barriers and allow strong immunity against various tumors without defining tumor antigens. This review summarizes recent findings to support that LIGHT is a promising candidate for an effective cancer immunotherapy.     

Comparing parasite numbers between samples of hosts

The comparison of parasite numbers or intensities between different samples of hosts is a common and important question in most parasitological studies. The main question is whether the values in one sample tend to be higher (or lower) than the values of the other sample. We argue that it is more appropriate to test a null hypothesis about the probability that an individual host from one sample has a higher value than individual hosts from a second sample rather than testing hypotheses about means or medians. We present a recently proposed statistical test especially designed to test hypotheses about that probability. This novel test is more appropriate than other statistical tests, such as Student's t-test, the Mann-Whitney U-test, or a bootstrap test based on Welch's t-statistic, regularly used by parasitologists.     

A model of encounters between host and parasite populations

A simulation model of the encounter between host and parasite populations is described. The model is two-dimensional in that it represents hosts and parasites as sums of random numbers. It allows for the manipulation of host and parasite numbers, areas of interaction, congruity of geographic ranges, parasite infectivity, and reproduction, or non-reproduction, of the parasite. The model generates parasite distributions (number of hosts vs. parasite/host classes) and their parameters (prevalence, mean number of parasites/host, variance/mean ratio as a measure of aggregation), and thus reveals the manner in which these parameters vary under different encounter conditions, i.e. their "behavior". Simulation results indicated that the behavior of parasite population mean, prevalence, and degree of aggregation was primarily a function of the rate at which infective stages were supplied to the system. In cases in which infective stages were continuously available, prevalence rose rapidly to nearly 100%, with increasing infectivity and parasite numbers, and the populations were not particularly aggregated. When infective stages were introduced in single large waves, both mean and prevalence remained low and the parasite populations were highly aggregated. Model results were compared with published data sets. The latter were also seen to fall into the two general categories of parameter behavior.     

Collective defence portfolios of ant hosts shift with social parasite pressure

Host defences become increasingly costly as parasites breach successive lines of defence. Because selection favours hosts that successfully resist parasitism at the lowest possible cost, escalating coevolutionary arms races are likely to drive host defence portfolios towards ever more expensive strategies. We investigated the interplay between host defence portfolios and social parasite pressure by comparing 17 populations of two Temnothorax ant species. When successful, collective aggression not only prevents parasitation but also spares host colonies the cost of searching for and moving to a new nest site. However, once parasites breach the host''s nest defence, host colonies should resort to flight as the more beneficial resistance strategy. We show that under low parasite pressure, host colonies more likely responded to an intruding Protomognathus americanus slavemaker with collective aggression, which prevented the slavemaker from escaping and potentially recruiting nest-mates. However, as parasite pressure increased, ant colonies of both host species became more likely to flee rather than to fight. We conclude that host defence portfolios shift consistently with social parasite pressure, which is in accordance with the degeneration of frontline defences and the evolution of subsequent anti-parasite strategies often invoked in hosts of brood parasites.     

Infection deflection: hosts control parasite location with behaviour to improve tolerance

Anti-parasite behaviour can reduce parasitic infections, but little is known about how such behaviours affect infection location within the host''s body and whether parasite distribution ultimately affects tolerance of infection. To assess these questions, we exposed both anaesthetized (no behaviour) and non-anaesthetized Hyla femoralis tadpoles to plagiorchiid cercariae (larval trematodes), and quantified resistance, tolerance (relationship between mass change and infection intensity) and encystment location. Non-anaesthetized tadpoles had significantly more infections in their tail region than anaesthetized tadpoles, which had the majority of their infections in the head. This pattern indicates that parasites preferred to infect the head, but that hosts shunted infections to the tail when possible. Furthermore, there was a significant effect of encystment location on tolerance, with head-infected tadpoles having poorer tolerance to infection than tail-infected tadpoles. Variance partitioning suggests that, among infected tadpoles, behaviour contributed more to tolerance than resistance. These results suggest that, in addition to using behaviour to resist parasites, H. femoralis tadpoles also use behaviour to enhance infection tolerance by deflecting infections posteriorly, away from their vital sensory organs. These findings highlight the need to assess how widespread and important behaviour is to the tolerance of infections.     

寄生植物对寄主的选择和影响

寄生植物对寄主的选择性与寄主营养物质的含量、合成的次生物质和硬度有关．多寄主存在的条件下,有利于寄生植物的生长发育．通过改变寄主光合产物的流向和影响寄主叶片的气孔调节,寄生植物对寄主生理和形态产生显著的影响．寄生植物的存在使植物群落的生物量、组成多样性和动态发生改变．大量研究显示．寄生植物对寄主的选择和影响与植食性动物对取食植物的选择和影响有很多相似之处．气候变化对寄生植物与寄主关系影响的研究还刚刚起步,寄生植物对寄主选择和影响的研究对有害寄生植物的防除和有益寄生植物的利用有重要的价值,应该重视和加强．     

The decay of similarity with geographical distance in parasite communities of vertebrate hosts

Aim The rate at which similarity in species composition decays with increasing distance was investigated among communities of parasitic helminths in different populations of the same host species. Rates of distance decay in similarity of parasite communities were compared between populations of fish and mammal hosts, which differ with respect to their vagility and potential to disperse parasite species over large distances. Location Data on helminth communities were compiled for several populations of three mammalian host species (Ondatra zibethicus, Procyon lotor and Canis latrans) and three fish host species (Perca flavescens, Catostomus commersoni and Esox lucius) from continental North America. Methods Distances between localities and similarity in the composition of helminth communities, the latter computed using the Jaccard index, were calculated for all possible pairs of host populations within each host species. Similarity values were then regressed against distance to see if they decayed at exponential rates, as reported for plant communities; the significance of the regressions was assessed using randomization tests. Results The number of hosts examined per population did not correlate with the number of helminth species found per population, and thus sampling effort is unlikely to have confounded the results. In four (two mammals and two fish) of the six host species, similarity in helminth communities decayed exponentially with distance. When the log of similarity is plotted against untransformed distance, the slopes obtained for the two fish species are lower than those obtained for the two mammalian host species. Main conclusions Similarity in the composition of parasite communities appears to decay exponentially with increasing distance in some host species, but not in all host species. The rate of decay is not necessarily associated with the vagility of the host. Although distance decay of similarity is generally occurring, it seems that other ecological processes, related either to the host or its habitat, can obscure it.     

A metapopulation model for malaria with transmission-blocking partial immunity in hosts

A metapopulation malaria model is proposed using SI and SIRS models for the vectors and hosts, respectively. Recovered hosts are partially immune to the disease and while they cannot directly become infectious again, they can still transmit the parasite to vectors. The basic reproduction number R₀{\mathcal{R}_0} is shown to govern the local stability of the disease free equilibrium but not the global behavior of the system because of the potential occurrence of a backward bifurcation. Using type reproduction numbers, we identify the reservoirs of infection and evaluate the effect of control measures. Applications to the spread to non-endemic areas and the interaction between rural and urban areas are given.     

寄生植物对寄主的选择和影响

寄生植物对寄主的选择性与寄主营养物质的含量、合成的次生物质和硬度有关.多寄主存在的条件下,有利于寄生植物的生长发育.通过改变寄主光合产物的流向和影响寄主叶片的气孔调节,寄生植物对寄主生理和形态产生显著的影响.寄生植物的存在使植物群落的生物量、组成多样性和动态发生改变.大量研究显示,寄生植物对寄主的选择和影响与植食性动物对取食植物的选择和影响有很多相似之处.气候变化对寄生植物与寄主关系影响的研究还刚刚起步,寄生植物对寄主选择和影响的研究对有害寄生植物的防除和有益寄生植物的利用有重要的价值,应该重视和加强.     

Cleaner fish become hosts: a novel form of parasite transmission

Adult bucephalid trematodes (Digenea) generally only occur in piscivorous fish. Within labrid fishes they are very rare, however, we have found them in labrid cleaner fish that feed on the ectoparasites of fish. We surveyed 969 labrid fishes from the tropical Pacific and found bucephalids only in cleaners (Labroides dimidiatus, L. bicolor, and Bodianus axillaris) and none in piscivores. The prevalences of bucephalids in L. dimidiatus at Lizard Island, Heron Island, Orpheus Island (all on the Great Barrier Reef), New Caledonia, and Moorea (French Polynesia) were 51, 47, 67, 56, and 67%, respectively. All of the L. bicolor examined from Moorea were infected. Bucephalids were highly prevalent in all size classes of L. dimidiatus from Lizard Island. Bucephalids were found in a 1.6-cm long juvenile L. dimidiatus, in which, piscivory is highly unlikely. We examined the literature on the worldwide bucephalid fauna in labrids and all hosts were found to be cleaners (Symphodus tinca, S. mediterraneus, L. dimidiatus, L. bicolor, and Bodianus axillaris) except Notolabrus parilus, whose ecology is unknown. We suggest that cleaners eat bucephalid metacercariae directly from the exterior surface of client fish during cleaning interactions. This is the first evidence of digeneans in the diet of L. dimidiatus, and the first study to show this novel form of parasite transmission where infective stages are eaten as a result of cleaning behaviour. Cleaning-mediated parasite transmission may result in behavioural modification of second intermediate hosts because clients and parasites both benefit from transmission. If the infection is costly to cleaners and acquired during cheating behaviour, then this parasite might regulate mutualism. Alternatively, if infective stages are targeted, infection by these bucephalids may be a negative consequence of an honest foraging strategy.Communicated by: P. F. Sale     

Native fish avoid parasite spillback from multiple exotic hosts: consequences of host density and parasite competency

Disease-mediated impacts of exotic species on their native counterparts are often ignored when parasite-free individuals are translocated. However, native parasites are frequently acquired by exotic species, thus providing a mechanism through which native host-parasite dynamics may be altered. In Argentina, multiple exotic salmonids are host to the native fish acanthocephalan parasite Acanthocephalus tumescens. Field evidence suggests that rainbow trout, Oncorhynchus mykiss, may be a major contributor to the native parasite’s population. We used a combination of experimental infections (cystacanth—juvenile worm transmission from amphipod to fish; post-cyclic—adult worm transmission between definitive fish hosts) and dynamic population modelling to determine the extent to which exotic salmonid hosts may alter A. tumescens infections in native freshwater fish. Experimental cystacanth infections demonstrated that although A. tumescens establishes equally well in native and exotic hosts, parasite growth and maturity is superior in exotic O. mykiss. Experimental post-cyclic infections also showed greater establishment success of A. tumescens in O. mykiss, though post-cyclic transmission did not result in greater parasite size or maturity. Dynamic population modelling, however, suggested that exotic salmonids may have a very limited influence on the A. tumescens population overall, due to the majority of A. tumescens individuals being maintained by more abundant native hosts. This research highlights the importance of considering both a host’s relative density and its competency for parasites when evaluating whether exotic species can modify native host-parasite dynamics.     

Different transmission strategies of a parasite in male and female hosts

We investigated whether a parasite with two routes of transmission responds to the different transmission opportunities offered by male and female hosts by using different transmission strategies in the two sexes. The parasite Ascogregarina culicis, which infects the mosquito Aedes aegypti, can be transmitted as its host’s pupa transforms into an adult or when a female lays its eggs. As the latter transmission route is missing in males, we expected, and found, that the parasite releases a greater proportion of its infectious forms during emergence when it is within a male than when it infects a female. The transmission route, which influences the parasite’s dispersal and the evolution of its virulence, was also affected by the dose of infection and the parasite’s previous transmission route. Our results emphasize the complexity underlying the development of parasites and show their ability to tune their strategy to their environment.     

Network position of hosts in food webs and their parasite diversity

Parasites are ubiquitous in ecological communities but it is only recently that they have been routinely included in food web studies. Using recently published data and the tool of network analysis, we elucidate features associated with the pattern of parasitism in ecological communities. First we show here that parasitism is non‐random in food webs. Second we demonstrate that parasite diversity, the number of parasite species harboured by a host species, is related to the network position of a host species. Specifically, a host species with high parasite diversity tends to have a wide diet range, occupy a network position close to many prey species, or occupy a network position that can better accumulate resources from species at lower trophic levels. Lastly our results also suggest that a host species with higher vulnerability to predators, being at a network position close to many predatory species, or being involved in many different food chains, tends to be important in parasite transmission.     

Evasion of phagotrophic predation by protist hosts and innate immunity of metazoan hosts by Legionella pneumophila

Legionella pneumophila is a ubiquitous environmental bacterium that has evolved to infect and proliferate within amoebae and other protists. It is thought that accidental inhalation of contaminated water particles by humans is what has enabled this pathogen to proliferate within alveolar macrophages and cause pneumonia. However, the highly evolved macrophages are equipped with more sophisticated innate defence mechanisms than are protists, such as the evolution of phagotrophic feeding into phagocytosis with more evolved innate defence processes. Not surprisingly, the majority of proteins involved in phagosome biogenesis (~80%) have origins in the phagotrophy stage of evolution. There are a plethora of highly evolved cellular and innate metazoan processes, not represented in protist biology, that are modulated by L. pneumophila, including TLR2 signalling, NF‐κB, apoptotic and inflammatory processes, histone modification, caspases, and the NLRC–Naip5 inflammasomes. Importantly, L. pneumophila infects haemocytes of the invertebrate Galleria mellonella, kill G. mellonella larvae, and proliferate in and kill Drosophila adult flies and Caenorhabditis elegans. Although coevolution with protist hosts has provided a substantial blueprint for L. pneumophila to infect macrophages, we discuss the further evolutionary aspects of coevolution of L. pneumophila and its adaptation to modulate various highly evolved innate metazoan processes prior to becoming a human pathogen.     

Distance decay of similarity among parasite communities of three marine invertebrate hosts

The similarity in species composition between two communities generally decays as a function of increasing distance between them. Parasite communities in vertebrate definitive hosts follow this pattern but the respective relationship in intermediate invertebrate hosts of parasites with complex life cycles is unknown. In intermediate hosts, parasite communities are affected not only by the varying vagility of their definitive hosts (dispersing infective propagules) but also by the necessary coincidence of all their hosts in environmentally suitable localities. As intermediate hosts often hardly move they do not contribute to parasite dispersal. Hence, their parasite assemblages may decrease faster in similarity with increasing distance than those in highly mobile vertebrate definitive hosts. We use published field survey data to investigate distance decay of similarity in trematode communities from three prominent coastal molluscs of the Eastern North-Atlantic: the gastropods Littorina littorea and Hydrobia ulvae, and the bivalve Cerastoderma edule. We found that the similarity of trematode communities in all three hosts decayed with distance, independently of local sampling effort, and whether or not the parasites used the mollusc as first or second intermediate host in their life cycle. In H. ulvae, the halving distance (i.e. the distance that halves the similarity from its initial similarity at 1 km distance) for the trematode species using birds as definitive hosts was approximately two to three times larger than for species using fish. The initial similarities (estimated at 1 km distance) among trematode communities were relatively higher, whereas mean halving distances were lower, compared to published values for parasite communities in vertebrate hosts. We conclude that the vagility of definitive hosts accounts for a high similarity at the local scale, while the strong decay of similarity across regions is a consequence of the low probability that all necessary hosts and suitable environmental conditions coincide on a large scale.     

Distribution of schistosome infections in molluscan hosts at different levels of parasite prevalence

Biomphalaria glabrata snails infected with Schistosoma mansoni were collected during consecutive seasons from a site in Brazil known to have a very high percentage of infected snails. Schistosoma mansoni cercariae from single snails were used to infect individual mice, and the recovered adult worms were genetically assessed using a mtVNTR marker. The number of unique parasite genotypes found per snail was compared to expected abundance values, based on the infection prevalence at the site, to determine the distribution of S. mansoni infections within the snail population. The observed distributions and those from previous studies were used to examine the relationship between schistosome prevalence and aggregation across a wide range of prevalence values. Our analysis showed that prevalence was inversely related to the degree of parasite overdispersion, and at high prevalence, S. mansoni infections were randomly distributed among snails.     

Two threats at once: encounters with predator cues alter host life-history and morphological responses to parasite spores

Parasites and predators are ubiquitous threats in every ecosystem. Host and prey species, respectively, have evolved effective protective mechanisms which are assumed to involve costs. In this study, we analyzed potential interactions between both threats. We exposed waterfleas (Daphnia longicephala) simultaneously to parasite spores (the yeast Metschnikowia) and cues from predatory notonectids (Notonecta glauca). In response to the parasite, D. longicephala had a delayed maturation time and produced less and smaller offspring, even though the parasite developed no spores. This suggests that hosts can successfully fight off the parasite invoking defensive costs. Some of these effects were altered or even reversed by the presence of predator cues. For example, time to maturity was further delayed when the Daphnia were exposed to both threats than under parasite stress alone. In addition, more offspring were produced in the presence of both threats, although parasites alone reduced their number. However, there was no effect of parasite exposure on the expression of morphological defenses. Our results imply that the impact of parasites on host species depends strongly on the presence of further threats. Similar types of experimental approaches may enhance our understanding of the effects of multiple stressors in natural systems.     

Tumor cells with B7.1 and transmembrane anchored staphylococcal enterotoxin A generate effective antitumor immunity

Staphylococcus enterotoxin A (SEA) stimulates T cells bearing certain TCR beta-chain variable regions, when bound to MHC-II molecules, and is a potent inducer of CTL activity and cytokines production. To decrease toxicity of SEA to the normal MHC-II(+) cells and to localize the immune response induced by SEA to the tumor site, my colleague previously genetically fused SEA with B7.1 transmembrane region (named as SEAtm) to make SEA express on the surface of tumor cells and tumor cells modified with SEAtm could induce efficient antitumor immunity in vitro. The tumor cell vaccines modified with multiple immune activators frequently elicited stronger antitumor immune responses than single-modified vaccines. In this study, we modified the tumor cell vaccine with B7.1 and SEAtm to improve efficiency in the application of SEA. First, SEAtm gene was subcloned from recombinant plasmid pLXSNSEP by PCR and murine B7.1 gene was cloned from splenocytes derived from C57BL/6 mice by RT-PCR. Then, the eukaryotic co-expression vector of SEA and murine B7.1 gene was constructed and named as pcDNA-BIS. B16 cell lines stably expressing SEA and/or B7.1 were established by screening with G418 after transfection and inactivated for the preparation of tumor cell vaccines to treat mice bearing established B16 tumors. The results indicated that the dual-modified tumor cell vaccine B16/B7.1+SEAtm (B16-BIS) elicited significantly stronger antitumor immune responses in vivo when compared with the single-modified tumor cell vaccines B16/B7.1 (B16-B7.1) and B16/SEAtm (B16-SEAtm), and supported the feasibility and effectiveness of the dual-modified tumor cell vaccine with superantigen and co-stimulatory molecule.