Avian malaria alters the dynamics of blood feeding in Culex pipiens mosquitoes.

BACKGROUND: Some Plasmodium species have the ability to modify the behaviour of their mosquito vectors. This is thought to be an adaptive strategy that maximizes the parasite's transmission. METHODS: The effect of Plasmodium relictum infections on the blood feeding behaviour of Culex pipiens quinquefasciatus mosquitoes was monitored. RESULTS: Plasmodium infections did not alter the proportion of blood fed mosquitoes but they did affect the dynamics and the size of the blood meal. Sporozoite-infected mosquitoes completed their blood meal 1.3 times later than uninfected mosquitoes and ended up with smaller blood meals. CONCLUSION: The potential adaptive nature of this manipulation of mosquito behaviour is discussed in the light of previous studies on other malaria models.

Early Plasmodium-induced inflammation does not accelerate aging in mice.

Aging is associated with a decline of performance leading to reduced reproductive output and survival. While the antagonistic pleiotropy theory of aging has attracted considerable attention, the molecular/physiological functions underlying the early-life benefits/late-life costs paradigm remain elusive. We tested the hypothesis that while early activation of the inflammatory response confers benefits in terms of protection against infection, it also incurs costs in terms of reduced reproductive output at old age and shortened longevity. We infected mice with the malaria parasite Plasmodium yoelii and increased the inflammatory response using an anti-IL-10 receptor antibody treatment. We quantified the benefits and costs of the inflammatory response during the acute phase of the infection and at old age. In agreement with the antagonistic pleiotropy hypothesis, the inflammatory response provided an early-life benefit, since infected mice that were treated with anti-IL-10 receptor antibodies had reduced parasite density and anemia. However, at old age, mice in all treatment groups had similar levels of C-reactive protein, reproductive output, survival rate, and lifespan. Overall, our results do not support the hypothesis that the benefits of a robust response to malaria infection in early life incur longer term fitness costs.

Eco-immunology and bioinvasion: revisiting the evolution of increased competitive ability hypotheses.

Immunity is at the core of major theories related to invasion biology. Among them, the evolution of increased competitive ability (EICA) and EICA-refined hypotheses have been used as a reference work. They postulate that the release from pathogens often experienced during invasion should favour a reallocation of resources from (costly) immune defences to beneficial life-history traits associated with invasive potential. We review studies documenting immune changes during animal invasions. We describe the designs and approaches that have been applied and discuss some reasons that prevent drawing generalized conclusions regarding EICA hypotheses. We detail why a better assessment of invasion history and immune costs, including immunopathologies and parasite communities, could improve our understanding of the relationships between immunity and invasion success. Finally, we propose new perspectives to revisit the EICA hypotheses. We first emphasize the neutral and adaptive mechanisms involved in immune changes, as well as timing of the later. Such investigation will help decipher whether immune changes are a consequence of pre-adaptation, or the result of postintroduction adaptations to invasion front conditions. We next bring attention to new avenues of research that remain unexplored, namely age-dependent immunity and gut microbiota, potential key factors underlying adaptation to invasion front environment and modulating invasion success.

Host immune responses to experimental infection of Plasmodium relictum (lineage SGS1) in domestic canaries (Serinus canaria).

Understanding the complexity of host immune responses to parasite infection requires controlled experiments that can inform observational field studies. Birds and their malaria parasites provide a useful model for understanding host-parasite relationships, but this model lacks a well-described experimental context for how hosts respond immunologically to infection. Here, ten canaries (Serinus canaria) were infected with the avian malaria parasite Plasmodium relictum (lineage SGS1) in a controlled laboratory setting with ten uninfected (control) birds. A suite of immunological blood parameters, including the concentration of four white blood cell types, the concentration of the acute phase protein haptoglobin, and the bacteria-killing ability of blood plasma, were repeatedly measured over a 25-day period covering the acute phase of a primary infection by P. relictum. Three infected and one control bird died during the course of the experiment. A multivariate statistical analysis of the immune indices revealed significant differences between infected and uninfected individuals between 5 and 14 days postinfection (dpi). Group differences corresponded to reduced concentrations of lymphocytes (5 dpi), heterophils (8 dpi), and monocytes (11 and 14 dpi), and an increase in haptoglobin (14 dpi), in infected birds relative to uninfected controls, and no change in bacteria-killing. Upon re-running the analysis with only the surviving birds, immunological differences between infected and control birds shifted to between 11 and 18 dpi. However, there were no clear correlates relating immune parameters to the likelihood of surviving the infection. The results presented here demonstrate the dynamic and complex nature of avian immune function during the acute phase of malaria infection and provide a context for studies investigating immune function in wild birds.

Avian malaria: a new lease of life for an old experimental model to study the evolutionary ecology of Plasmodium.

Avian malaria has historically played an important role as a model in the study of human malaria, being a stimulus for the development of medical parasitology. Avian malaria has recently come back to the research scene as a unique animal model to understand the ecology and evolution of the disease, both in the field and in the laboratory. Avian malaria is highly prevalent in birds and mosquitoes around the world and is amenable to laboratory experimentation at each stage of the parasite's life cycle. Here, we take stock of 5 years of experimental laboratory research carried out using Plasmodium relictum SGS1, the most prevalent avian malaria lineage in Europe, and its natural vector, the mosquito Culex pipiens. For this purpose, we compile and analyse data obtained in our laboratory in 14 different experiments. We provide statistical relationships between different infection-related parameters, including parasitaemia, gametocytaemia, host morbidity (anaemia) and transmission rates to mosquitoes. This analysis provides a wide-ranging picture of the within-host and between-host parameters that may bear on malaria transmission and epidemiology.

Evolution of plastic transmission strategies in avian malaria.

Malaria parasites have been shown to adjust their life history traits to changing environmental conditions. Parasite relapses and recrudescences--marked increases in blood parasite numbers following a period when the parasite was either absent or present at very low levels in the blood, respectively--are expected to be part of such adaptive plastic strategies. Here, we first present a theoretical model that analyses the evolution of transmission strategies in fluctuating seasonal environments and we show that relapses may be adaptive if they are concomitant with the presence of mosquitoes in the vicinity of the host. We then experimentally test the hypothesis that Plasmodium parasites can respond to the presence of vectors. For this purpose, we repeatedly exposed birds infected by the avian malaria parasite Plasmodium relictum to the bites of uninfected females of its natural vector, the mosquito Culex pipiens, at three different stages of the infection: acute (∼ 34 days post infection), early chronic (∼ 122 dpi) and late chronic (∼ 291 dpi). We show that: (i) mosquito-exposed birds have significantly higher blood parasitaemia than control unexposed birds during the chronic stages of the infection and that (ii) this translates into significantly higher infection prevalence in the mosquito. Our results demonstrate the ability of Plasmodium relictum to maximize their transmission by adopting plastic life history strategies in response to the availability of insect vectors.

Impact of host nutritional status on infection dynamics and parasite virulence in a bird-malaria system.

Host resources can drive the optimal parasite exploitation strategy by offering a good or a poor environment to pathogens. Hosts living in resource-rich habitats might offer a favourable environment to developing parasites because they provide a wealth of resources. However, hosts living in resource-rich habitats might afford a higher investment into costly immune defences providing an effective barrier against infection. Understanding how parasites can adapt to hosts living in habitats of different quality is a major challenge in the light of the current human-driven environmental changes. We studied the role of nutritional resources as a source of phenotypic variation in host exploitation by the avian malaria parasite Plasmodium relictum. We investigated how the nutritional status of birds altered parasite within-host dynamics and virulence, and how the interaction between past and current environments experienced by the parasite accounts for the variation in the infection dynamics. Experimentally infected canaries were allocated to control or supplemented diets. Plasmodium parasites experiencing the two different environments were subsequently transmitted in a full-factorial design to new hosts reared under similar control or supplemented diets. Food supplementation was effective since supplemented hosts gained body mass during a 15-day period that preceded the infection. Host nutrition had strong effects on infection dynamics and parasite virulence. Overall, parasites were more successful in control nonsupplemented birds, reaching larger population sizes and producing more sexual (transmissible) stages. However, supplemented hosts paid a higher cost of infection, and when keeping parasitaemia constant, they had lower haematocrit than control hosts. Parasites grown on control hosts were better able to exploit the subsequent hosts since they reached higher parasitaemia than parasites originating from supplemented hosts. They were also more virulent since they induced higher mass and haematocrit loss. Our study highlights that parasite virulence can be shaped by the host nutritional status and that parasite can adapt to the environment provided by their hosts, possibly through genetic selection.

Food availability and competition do not modulate the costs of Plasmodium infection in dominant male canaries.

Understanding the different factors that may influence parasite virulence is of fundamental interest to ecologists and evolutionary biologists. It has recently been demonstrated that parasite virulence may occur partly through manipulation of host competitive ability. Differences in competitive ability associated with the social status (dominant or subordinate) of a host may determine the extent of this competition-mediated parasite virulence. We proposed that differences between subordinate and dominant birds in the physiological costs of infection may change depending on the level of competition in social groups. We observed flocks of domestic canaries to determine dominant or subordinate birds, and modified competition by providing restricted (high competition) or ad libitum food (low competition). Entire flocks were then infected with either the avian malaria parasite, Plasmodium relictum or a control. Contrary to our predictions we found that the level of competition had no effect on the outcome of infection for dominant or subordinate birds. We found that dominant birds appeared to suffer greater infection mediated morbidity in both dietary treatments, with a higher and more sustained reduction in haematocrit, and higher parasitaemia, than subordinates. Our results show that dominance status in birds can certainly alter parasite virulence, though the links between food availability, competition, nutrition and virulence are likely to be complex and multifaceted.

Both infected and uninfected mosquitoes are attracted toward malaria infected birds.

BACKGROUND: The biting behaviour of mosquitoes is crucial for the transmission of malaria parasites. This study focuses on the feeding behaviour of Culex pipiens mosquitoes with regard to the infection status by the avian malaria parasite Plasmodium relictum (lineage SGS1). METHODS: Uninfected and sporozoite-infected mosquitoes were provided with a choice between an uninfected bird and a bird undergoing a chronic P. relictum infection. Mosquito choice is assessed by microsatellite typing of the ingested blood. RESULTS: Chronically infected birds are more attractive to mosquitoes. This choice is not altered by the infection status of the mosquitoes: both infected and uninfected mosquitoes have similar host choice behaviours and are more attracted towards infected birds. CONCLUSIONS: These results support some, but not all predictions derived from the hypothesis that malaria parasites can manipulate the behaviour of their mosquito vectors to enhance their transmission. The possible mechanisms driving this manipulation, the evolutionary dynamics leading to the modification of the biting behaviour of mosquitoes by Plasmodium sp. as well as the implications for malaria epidemiology are discussed.

Immunity and the emergence of virulent pathogens.

The emergence/re-emergence of infectious diseases has been one of the major concerns for human and wildlife health. In spite of the medical and veterinary progresses as to prevent and cure infectious diseases, during the last decades we have witnessed the emergence/re-emergence of virulent pathogens that pose a threat to humans and wildlife. Many factors that might drive the emergence of these novel pathogens have been identified and several reviews have been published on this topic in the last years. Among the most cited and recognized drivers of pathogen emergence are climate change, habitat destruction, increased contact with reservoirs, etc. These factors mostly refer to environmental determinants of emergence. However, the immune system of the host is probably the most important environmental trait parasites have to cope with. Here, we wish to discuss how immune-mediated selection might affect the emergence/re-emergence of infectious diseases and drive the evolution of disease severity. Vaccination, natural (age-associated) and acquired immunodeficiencies, organ transplantation, environmental contamination with chemicals that disrupt immune functions form populations of hosts that might exert specific immune-mediated selection on a range of pathogens, shaping their virulence and evolution, and favoring their spread to other populations of hosts.

Immune evasion, immunopathology and the regulation of the immune system.

Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths) that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

Patterns of phenoloxidase activity in insecticide resistant and susceptible mosquitoes differ between laboratory-selected and wild-caught individuals.

BACKGROUND: Insecticide resistance has the potential to alter vector immune competence and consequently affect the transmission of diseases. METHODS: Using both laboratory isogenic strains and field-caught Culex pipiens mosquitoes, we investigated the effects of insecticide resistance on an important component of the mosquito immune system: the phenoloxidase (PO) activity. As infection risk varies dramatically with the age and sex of mosquitoes, allocation to PO immunity was quantified across different stages of the mosquito life cycle. RESULTS: Our results were consistent in showing that larvae have a higher PO activity than adults, females have a higher PO activity than males, and PO activity declines with adult age. We obtained, however, a marked discrepancy between laboratory and field-collected mosquitoes on the effect of insecticide resistance on PO activity. In the laboratory selected strains we found evidence of strong interactions between insecticide resistance and the age and sex of mosquitoes. In particular, 7 and 14 day old esterase-resistant adult females and acetylcholine-esterase resistant males had significantly higher PO activities than their susceptible counterparts. No such effects were, however, apparent in field-caught mosquitoes. CONCLUSIONS: Combined, the field and laboratory-based approaches employed in this study provide a powerful test of the effect of insecticide resistance on PO-mediated immunity. The use of laboratory-selected insecticide-resistant strains is still the most widely used method to investigate the pleiotropic effects of insecticide resistance. Our results suggest that the outcome of these laboratory-selected mosquitoes must be interpreted with caution and, whenever possible, compared with mosquitoes captured from the field.

Malaria infection increases bird attractiveness to uninfected mosquitoes.

The epidemiology of vector-borne pathogens is largely determined by the host-choice behaviour of their vectors. Here, we investigate whether a Plasmodium infection renders the host more attractive to host-seeking mosquitoes. For this purpose, we work on a novel experimental system: the avian malaria parasite Plasmodium relictum, and its natural vector, the mosquito Culex pipiens. We provide uninfected mosquitoes with a choice between an uninfected bird and a bird undergoing either an acute or a chronic Plasmodium infection. Mosquito choice is assessed by microsatellite typing of the ingested blood. We show that chronically infected birds attract significantly more vectors than either uninfected or acutely infected birds. Our results suggest that malaria parasites manipulate the behaviour of uninfected vectors to increase their transmission. We discuss the underlying mechanisms driving this behavioural manipulation, as well as the broader implications of these effects for the epidemiology of malaria.

Experimental inhibition of nitric oxide increases Plasmodium relictum (lineage SGS1) parasitaemia.

Malaria is a widespread vector-borne disease infecting a wide range of terrestrial vertebrates including reptiles, birds and mammals. In addition to being one of the most deadly infectious diseases for humans, malaria is a threat to wildlife. The host immune system represents the main defence against malaria parasites. Identifying the immune effectors involved in malaria resistance has therefore become a major focus of research. However, this has mostly involved humans and animal models (rodents) and how the immune system regulates malaria progression in non-model organisms has been largely ignored. The aim of the present study was to investigate the role of nitric oxide (NO) as an immune effector contributing to the control of the acute phase of infection with the avian malaria agent Plasmodium relictum. We used experimental infections of domestic canaries in conjunction with the inhibition of the enzyme inducible nitric oxide synthase (iNOS) to assess the protective function of NO during the infection, and the physiological costs paid by the host in the absence of an effective NO response. Our results show that birds treated with the iNOS inhibitor suffered from a higher parasitaemia, but did not pay a higher cost of infection (anaemia). While these findings confirm that NO contributes to the resistance to avian malaria during the acute phase of the infection, they also suggest that parasitaemia and costs of infection can be decoupled.

Density-dependent effects on parasite growth and parasite-induced host immunodepression in the larval helminth Pomphorhynchus laevis.

Larval helminths exploit the physiology of their intermediate hosts: first, as a resource for energy and space and second by altering the immune system activity to ensure their survival. Whereas the growth pattern under parasite competition has been investigated, the effect of multiple infections on the level of parasite-induced immunodepression in a trophically transmitted helminth has been neglected. In this study, amphipods Gammarus pulex were infected in the laboratory by the acanthocephalan Pomphorhynchus laevis to investigate how parasite density in the intermediate host affected (i) cystacanth growth and (ii) the level of parasite-induced alterations of the host immune defences, two traits strongly linked to host exploitation. The study highlights that sharing a host is costly. As parasite intensity increases, competition for resources translates into a reduction in cystacanth volume. Immune manipulation is also modulated by density. Interestingly, immunodepression is higher in double-infected hosts compared to hosts with a single infection, suggesting an opportunity for cooperative immune manipulation. However, in higher multiple infections, parasites do not further down-regulate the host immune response, possibly to avoid additional costs that may outweigh the benefits of immunodepression.

Variation between populations and local adaptation in acanthocephalan-induced parasite manipulation.

Many trophically transmitted parasites manipulate their intermediate host phenotype, resulting in higher transmission to the final host. However, it is not known if manipulation is a fixed adaptation of the parasite or a dynamic process upon which selection still acts. In particular, local adaptation has never been tested in manipulating parasites. In this study, using experimental infections between six populations of the acanthocephalan parasite Pomphorhynchus laevis and its amphipod host Gammarus pulex, we investigated whether a manipulative parasite may be locally adapted to its host. We compared adaptation patterns for infectivity and manipulative ability. We first found a negative effect of all parasite infections on host survival. Both parasite and host origins influenced infection success. We found a tendency for higher infectivity in sympatric versus allopatric combinations, but detailed analyses revealed significant differences for two populations only. Conversely, no pattern of local adaptation was found for behavioral manipulation, but manipulation ability varied among parasite origins. This suggests that parasites may adapt their investment in behavioral manipulation according to some of their host's characteristics. In addition, all naturally infected host populations were less sensitive to parasite manipulation compared to a naive host population, suggesting that hosts may evolve a general resistance to manipulation.

Parasite virulence when the infection reduces the host immune response.

Parasite infections often induce a reduction in host immune response either because of a direct manipulation of the immune system by the parasite or because of energy depletion. Although infection-induced immunodepression can favour the establishment of the parasite within the host, a too severe immunodepression may increase the risk of infection with opportunistic pathogens, stopping the period over which the parasite can be transmitted to other hosts. Here, we explore how the risk of contracting opportunistic diseases affects the survival of the amphipod Gammarus pulex infected by the acanthocephalan Pomphorhynchus laevis. Previous work with this system has shown that upon infection, G. pulex has a substantially reduced immune response. Non-infected and P. laevis-infected hosts were maintained either in control or in micro-organism-enriched water, so as to vary the risk of encountering opportunistic pathogens. As predicted, we found that host mortality was exacerbated when infected gammarids were maintained in micro-organism-enriched water compared with clean, control water; whereas for non-infected gammarids, living in micro-organism-enriched water only moderately increased the risk of mortality. These results show that the virulence of parasites that reduce the host immune response is an environmentally sensitive trait that depends on the concomitant risk for the host of contracting opportunistic diseases. This extra source of host mortality probably represents a cost for P. laevis, and we tentatively predict that the optimal level of parasite exploitation should depend on environmental conditions.

Patterns of aging in the long-lived wandering albatross.

How does an animal age in natural conditions? Given the multifaceted nature of senescence, identifying the effects of age on physiology and behavior remains challenging. We investigated the effects of age on a broad array of phenotypic traits in a wild, long-lived animal, the wandering albatross. We studied foraging behavior using satellite tracking and activity loggers in males and females (age 6-48+ years), and monitored reproductive performance and nine markers of baseline physiology known to reflect senescence in vertebrates (humoral immunity, oxidative stress, antioxidant defenses, and hormone levels). Age strongly affected foraging behavior and reproductive performance, but not baseline physiology. Consistent with results of mammal and human studies, age affected males and females differently. Overall, our findings demonstrate that age, sex, and foraging ability interact in shaping aging patterns in natural conditions. Specifically, we found an unexpected pattern of spatial segregation by age; old males foraged in remote Antarctica waters, whereas young and middle-aged males never foraged south of the Polar Front. Old males traveled a greater distance but were less active at the sea surface, and returned from sea with elevated levels of stress hormone (corticosterone), mirroring a low foraging efficiency. In contrast to findings in captive animals and short-lived birds, and consistent with disposable soma theory, we found no detectable age-related deterioration of baseline physiology in albatrosses. We propose that foraging efficiency (i.e., the ability of individuals to extract energy from their environment) might play a central role in shaping aging patterns in natural conditions.

Variation and covariation in infectivity, virulence and immunodepression in the host-parasite association Gammarus pulex-Pomphorhynchus laevis.

Parasites often manipulate host immunity for their own benefit, either by exacerbating or suppressing the immune response and this may directly affect the expression of parasite virulence. However, genetic variation in immunodepression, which is a prerequisite to its evolution, and the relationship between immunodepression and virulence, have rarely been studied. Here, we investigated the variation among sibships of the acanthocephalan parasite, Pomphorhynchus laevis, in infecting and in immunodepressing its amphipod host, Gammarus pulex. We also assessed the covariation between infectivity, parasite-induced immune depression and host mortality (parasite virulence). We found that infectivity, the intensity of immunodepression and virulence were variable among parasite sibships. Infectivity and the level of immunodepression were not correlated across parasite sibships. Whereas infectivity was unrelated to host mortality, we found that gammarids that were exposed to the parasite sibships that immunodepressed their hosts the most survived better. This positive covariation between host survival and immunodepression suggests that gammarids exposed to the less immunodepressive parasites could suffer from damage imposed by a higher activity of the phenoloxidase.

Immune depression induced by acanthocephalan parasites in their intermediate crustacean host: consequences for the risk of super-infection and links with host behavioural manipulation.

Parasite survival in hosts mainly depends on the capacity to circumvent the host immune response. Acanthocephalan infections in gammarids are linked with decreased activity of the prophenoloxidase (ProPO) system, suggesting an active immunosuppression process. Nevertheless, experimental evidence for this hypothesis is lacking: whether these parasites affect several immune pathways is unknown and the consequences of such immune change have not been investigated. In particular, the consequences for other pathogens are not known; neither are the links with other parasite-induced manipulations of the host. Firstly, using experimental infections of Pomphorhynchus laevis we confirmed that the lower immune activity in parasitised Gammarus pulex is induced by the parasite infection. Second, using natural infections of three different parasites, P. laevis, Pomphorhynchus tereticollis and Polymorphus minutus, we showed that acanthocephalan infection was associated with reduction of the activity of the ProPO system and the haemocyte concentration (two major parameters of crustacean immunity) suggesting that immune depression is a phenomenon affecting several immunological activities. This was confirmed by the fact that acanthocephalan infection (whatever the parasite species) was linked to a lower efficiency to eliminate a bacterial infection. The result suggests a cost of parasite immune depression. Finally, acanthocephalans are also known to induce behavioural alterations in the intermediate host which favour their transmission to definitive hosts. We did not find any correlation between behavioural and immunological alterations in both experimentally and naturally-infected gammarids. Overall, this study suggests that whilst immune depression might be beneficial to acanthocephalan survival within the intermediate gammarid host, it might also be costly if it increases host mortality to additional infections before transmission of the parasite.