Increased Host Mortality Research Articles

Epithelial-intrinsic IKKα expression regulates group 3 innate lymphoid cell responses and antibacterial immunity.

Innate lymphoid cells (ILCs) are critical for maintaining epithelial barrier integrity at mucosal surfaces; however, the tissue-specific factors that regulate ILC responses remain poorly characterized. Using mice with intestinal epithelial cell (IEC)-specific deletions in either inhibitor of κB kinase (IKK)α or IKKβ, two critical regulators of NFκB activation, we demonstrate that IEC-intrinsic IKKα expression selectively regulates group 3 ILC (ILC3)-dependent antibacterial immunity in the intestine. Although IKKβ(ΔIEC) mice efficiently controlled Citrobacter rodentium infection, IKKα(ΔIEC) mice exhibited severe intestinal inflammation, increased bacterial dissemination to peripheral organs, and increased host mortality. Consistent with weakened innate immunity to C. rodentium, IKKα(ΔIEC) mice displayed impaired IL-22 production by RORγt(+) ILC3s, and therapeutic delivery of rIL-22 or transfer of sort-purified IL-22-competent ILCs from control mice could protect IKKα(ΔIEC) mice from C. rodentium-induced morbidity. Defective ILC3 responses in IKKα(ΔIEC) mice were associated with overproduction of thymic stromal lymphopoietin (TSLP) by IECs, which negatively regulated IL-22 production by ILC3s and impaired innate immunity to C. rodentium. IEC-intrinsic IKKα expression was similarly critical for regulation of intestinal inflammation after chemically induced intestinal damage and colitis. Collectively, these data identify a previously unrecognized role for epithelial cell-intrinsic IKKα expression and TSLP in regulating ILC3 responses required to maintain intestinal barrier immunity.

Sphingomyelinase D inhibits store-operated Ca2+ entry in T lymphocytes by suppressing ORAI current

Infections caused by certain bacteria including Mycobacterium tuberculosis and Corynebacterium pseudotuberculosis provoke inflammatory responses characterized by the formation of granulomas with necrotic foci-so-called caseous necrosis. The granulomas of infected animals show prominent infiltration by T lymphocytes, and T cell depletion increases host mortality. Notorious zoonotic C. pseudotuberculosis secretes sphingomyelinase (SMase) D, a phospholipase that cleaves off the choline moiety of sphingomyelin, a phospholipid found primarily in the outer leaflet of host cell plasma membranes. Experimental C. pseudotuberculosis strains that lack SMase D are markedly less infectious and unable to spread in hosts, indicating that this enzyme is a crucial virulence factor for sustaining the caseous lymphadenitis infections caused by this microbe. However, the molecular mechanism by which SMase D helps bacteria evade the host's immune response remains unknown. Here, we find that SMase D inhibits store-operated Ca(2+) entry (SOCE) in human T cells and lowers the production of the SOCE-dependent cytokines interleukin-2, which is critical for T cell growth, proliferation, and differentiation, and tumor necrosis factor α, which is crucial for the formation and maintenance of granulomas in microbial infections. SMase D inhibits SOCE through a previously unknown mechanism, namely, suppression of Orai1 current, rather than through altering gating of voltage-gated K(+) channels. This finding suggests that, whereas certain genetic mutations abolish Orai1 activity causing severe combined immunodeficiency (SCID), bacteria have the ability to suppress Orai1 activity with SMase D to create an acquired, chronic SCID-like condition that allows persistent infection. Thus, in an example of how virulence factors can disrupt key membrane protein function by targeting phospholipids in host cell membranes, our study has uncovered a novel molecular mechanism that bacteria can use to thwart host immunity.

Leprosy and tuberculosis concomitant infection: A poorly understood, age-old relationship

Historically, archaeological evidence, post-mortem findings and retrospective analysis of leprosy institutions' data demonstrates a high observed incidence of concomitant infection with leprosy and tuberculosis (TB). However, reports of concomitant infection in the modern literature remain scarce, with estimates of annual new case detection rates of concomitant infection at approximately 0.02 cases per 100,000 population. Whilst the mechanism for this apparent decline in concomitant infections remains unclear, further research on this topic has remained relatively neglected. Modelling of the interaction of the two organisms has suggested that the apparent decline in observations of concomitant infection may be due to the protective effects of cross immunity, whilst more recently others have questioned whether it is a more harmful relationship, predisposing towards increased host mortality. We review recent evidence, comparing it to previously held understanding on the epidemiological relationship and our own experience of concomitant infection. From this discussion, we highlight several under-investigated areas, which may lead to improvements in the future delivery of leprosy management and services, as well as enhance understanding in other fields of infection management. These include, a) highlighting the need for greater understanding of host immunogenetics involved in concomitant infection, b) whether prolonged courses of high dose steroids pre-dispose to TB infection? and, c) whether there is a risk of rifampicin resistance developing in leprosy patients treated in the face of undiagnosed TB and other infections? Longitudinal work is still required to characterise these temporal relationships further and add to the current paucity of literature on this subject matter.

Indirect positive effects of a parasitic plant on host pollination and seed dispersal

Parasitic plants often have a strong fitness‐impact on their plant hosts through increased host mortality and reduced or complete suppression of reproduction. Tristerix corymbosus (Loranthaceae) is a hemiparasitic mistletoe that infects a wide range of host species along its distribution range. Among such species, Rhaphithamnus spinosus (Verbenaceae) is a frequent host with a flowering and fruiting season partially synchronized with mistletoe reproductive phenology. As parasitized hosts have, in principle, a larger flower display and fruit crop size than non‐parasitized hosts, we examined whether host and parasite reproductive synchrony make infected hosts more attractive for pollinators and seed dispersers than uninfected hosts. Our results showed that pollinator visit rates did not differ between parasitized and non‐parasitized hosts. Conversely, seed rain was higher in parasitized than non‐parasitized individuals. The number of seeds fallen under non‐parasitized plants was spatially associated with crop size, while parasitized plants did not show such association. Finally, the number of seedlings of R. spinosus was significantly larger near parasitized than non‐parasitized hosts. Our results suggest that the presence of the mistletoe might be responsible of the higher reproductive success showed by the parasitized fraction of R. spinosus. This effect, however, seems to be related to seed dispersal processes rather than pollination effects.

Influence of multiple infection and relatedness on virulence: disease dynamics in an experimental plant population and its castrating parasite.

The level of parasite virulence, i.e., the decrease in host's fitness due to a pathogen, is expected to depend on several parameters, such as the type of the disease (e.g., castrating or host-killing) and the prevalence of multiple infections. Although these parameters have been extensively studied theoretically, few empirical data are available to validate theoretical predictions. Using the anther smut castrating disease on Silene latifolia caused by Microbotryum lychnidis-dioicae, we studied the dynamics of multiple infections and of different components of virulence (host death, non-recovery and percentage of castrated stems) during the entire lifespan of the host in an experimental population. We monitored the number of fungal genotypes within plants and their relatedness across five years, using microsatellite markers, as well as the rates of recovery and host death in the population. The mean relatedness among genotypes within plants remained at a high level throughout the entire host lifespan despite the dynamics of the disease, with recurrent new infections. Recovery was lower for plants with multiple infections compared to plants infected by a single genotype. As expected for castrating parasites, M. lychnidis-dioicae did not increase host mortality. Mortality varied across years but was generally lower for plants that had been diseased the preceding year. This is one of the few studies to have empirically verified theoretical expectations for castrating parasites, and to show particularly i) that castrated hosts live longer, suggesting that parasites can redirect resources normally used in reproduction to increase host lifespan, lengthening their transmission phase, and ii) that multiple infections increase virulence, here in terms of non-recovery and host castration.

Metapopulation Dynamics of the Mistletoe and Its Host in Savanna Areas with Different Fire Occurrence

Mistletoes are aerial hemiparasitic plants which occupy patches of favorable habitat (host trees) surrounded by unfavorable habitat and may be possibly modeled as a metapopulation. A metapopulation is defined as a subdivided population that persists due to the balance between colonization and extinction in discrete habitat patches. Our aim was to evaluate the dynamics of the mistletoe Psittacanthus robustus and its host Vochysia thyrsoidea in three Brazilian savanna areas using a metapopulation approach. We also evaluated how the differences in terms of fire occurrence affected the dynamic of those populations (two areas burned during the study and one was fire protected). We monitored the populations at six-month intervals. P. robustus population structure and dynamics met the expected criteria for a metapopulation: i) the suitable habitats for the mistletoe occur in discrete patches; (ii) local populations went extinct during the study and (iii) colonization of previously non-occupied patches occurred. The ratio of occupied patches decreased in all areas with time. Local mistletoe populations went extinct due to two different causes: patch extinction in area with no fire and fire killing in the burned areas. In a burned area, the largest decrease of occupied patch ratios occurred due to a fire event that killed the parasites without, however, killing the host trees. The greatest mortality of V. thyrsoidea occurred in the area without fire. In this area, all the dead trees supported mistletoe individuals and no mortality was observed for parasite-free trees. Because P. robustus is a fire sensitive species and V. thyrsoidea is fire tolerant, P. robustus seems to increase host mortality, but its effect is lessened by periodic burning that reduces the parasite loads.

Innate lymphoid cells promote airway epithelial repair through the amphiregulin-EGFR pathway (P3250)

Abstract Innate lymphoid cells (ILCs) are a recently described group of immune cells that regulate immunity and inflammation at barrier surfaces. While recent studies have implicated Group 2 ILCs as initiators of pathologic Type 2 airway inflammation, the tissue-protective roles of ILCs in the respiratory tract remain poorly understood. Using genome-wide transcriptional profiling, we identify that naïve lung-resident group 2 ILCs express multiple genes associated with tissue repair pathways, including the epidermal growth factor family member amphiregulin. Amphiregulin was increased in a model of influenza virus-induced lung injury and ILC depletion during infection resulted in decreased amphiregulin expression, reduced lung function and impaired airway remodeling. IL-33 promoted expression of amphiregulin in lung ILCs and administration of amphiregulin effectively restored airway tissue remodeling in ILC-depleted mice, suggesting that ILC-intrinsic amphiregulin is a central mediator of epithelial repair. Supporting this, chemical or genetic inhibition of the EGFR-amphiregulin pathway resulted in severely impaired lung function and a failure to restore airway tissue homeostasis, leading to increased host mortality. Taken together, these data indicate a critical role for group 2 ILCs in mediating lung tissue homeostasis though an IL-33-amphiregulin-EGFR axis and suggest that ILCs serve as a key link between the signaling pathways of Type 2 inflammation and tissue repair.

Heme Oxygenase Inhibition Enhances Neutrophil Migration Into the Bronchoalveolar Spaces and Improves the Outcome of Murine Pneumonia-Induced Sepsis

A reduction of the neutrophil migration into the site of infection during cecal ligation and puncture-induced sepsis increases host mortality. Inhibition of heme oxygenase (HO) prevents this neutrophil paralysis and improves host survival in the cecal ligation and puncture model. Taking into account that almost 50% of all sepsis cases are a consequence of pneumonia, we designed the present study to determine the role of HO in an experimental model of pneumonia-induced sepsis. The objective of this study was to evaluate whether the inhibition of HO improves the outcome and pathophysiologic changes of sepsis induced by an intratracheal instillation of Klebsiella pneumoniae. The pretreatment of mice subjected to pneumonia-induced sepsis with ZnDPBG (zinc deuteroporphyrin 2,4-bis glycol), a nonspecific HO inhibitor, increased the number of neutrophils in the bronchoalveolar spaces, reduced the bacterial load at the site of infection, and prevented the upregulation of CD11b and the downregulation of CXCR2 on blood neutrophils. Moreover, the pretreatment with ZnDPBG decreased alveolar collapse, attenuating the deleterious changes in pulmonary mechanics and gas exchanges and, as a consequence, improved the survival rate of mice from 0% to ∼20%. These results show that heme oxygenase is involved in the pathophysiology of pneumonia-induced sepsis and suggest that HO inhibitors could be helpful for the management of this disease.

Unexpected Consequences of Culling on the Eradication of Wildlife Diseases: The Role of Virulence Evolution

The removal of individuals from an infected population (culling) is a common strategy used to eradicate wildlife diseases. The manipulation of host density can impose strong selective pressures on pathogen virulence by changing the ecological conditions, thus affecting the effectiveness of eradication programs. We present an analysis of the effect of virulence evolution on culling by extending a susceptible-infected model to the case of competing strains with superinfection. To assess both short- and long-term effects, we first carried out the analysis on an ecological timescale, with a two-strain competition model; then we explore the dynamics of a continuum of pathogenic strains on evolutionary timescales using a quantitative genetics approach (when infection and evolutionary processes occur on comparable timescales) and a game-theoretic approach (when evolutionary processes occur on a slower scale). We demonstrate that the competition among pathogenic variants in the presence of superinfection affects outcome of culling campaigns, since increased host mortality may select for less virulent strains able to establish in sparser populations. This can lead to the counterintuitive result that disease abundance and prevalence may even increase with culling, thus making the eradication of infections considerably less likely. This is particularly relevant in the case of zoonoses where higher prevalence and abundance of pathogens in wild reservoirs may increase the risk of spillover in livestock and humans.

Prevalence of infection as a predictor of multiple genotype infection frequency in parasites with multiple‐host life cycle

In nature, parasites commonly share hosts with other conspecific parasite genotypes. While adult parasites typically show aggregated distribution in their final hosts, aggregation of clonal parasite genotypes in intermediate hosts, such as those of trematodes in molluscs, is not generally known. However, infection of a host by multiple parasite genotypes has significant implications for evolution of virulence and host-parasite coevolution. Aggregated distribution of the clonal stages can increase host mortality and reduce larval output of each infecting genotype through interclonal competition, and therefore have significant implications for parasite epidemiology. The aim of this study was (i) to find out how common multiple genotype infections (MGIs) are in aquatic snails serving as intermediate hosts for different trematode species; (ii) to find out whether the prevalence of infection could be used to predict MGI frequencies and (iii) to use the relationship to infer whether MGIs aggregate in molluscan hosts. We determined the prevalence of trematode (Diplostomum pseudospathaceum) infections and the frequency of MGIs in snail (Lymnaea stagnalis) host populations as well as compiled corresponding literature data from a range of snail-trematode systems. We used Bayesian simulations to explore the relationship between prevalence of infection and MGI frequency in these data, and tested whether genotypes aggregate in snails by comparing the simulated relations with null model (Poisson and demographic Poisson) expectations. Our results show that MGIs are common in aquatic snails with up to 90% of the infected snails carrying MGIs. Parasite prevalence is a good predictor of MGI frequencies at a range of prevailing natural prevalences of infection (0-50%). The frequency of MGIs was higher than expected by both null models, indicating parasite aggregation at genotype level. These findings are in sharp contrast with the absence of multiple infections in snails at level of trematode species, suggesting that co-infections by multiple species and multiple genotypes of one species are controlled by different biological processes. Aggregation of MGIs in snail hosts appears to be widespread across different snail-trematode systems.

Wolbachia in a major African crop pest increases susceptibility to viral disease rather than protects

Wolbachia are common vertically transmitted endosymbiotic bacteria found in < 70% of insect species. They have generated considerable recent interest due to the capacity of some strains to protect their insect hosts against viruses and the potential for this to reduce vector competence of a range of human diseases, including dengue. In contrast, here we provide data from field populations of a major crop pest, African armyworm (Spodoptera exempta), which show that the prevalence and intensity of infection with a nucleopolydrovirus (SpexNPV) is positively associated with infection with three strains of Wolbachia. We also use laboratory bioassays to demonstrate that infection with one of these strains, a male-killer, increases host mortality due to SpexNPV by 6-14 times. These findings suggest that rather than protecting their lepidopteran host from viral infection, Wolbachia instead make them more susceptible. This finding potentially has implications for the biological control of other insect crop pests.

Commensal Bacteria Calibrate the Activation Threshold of Innate Antiviral Immunity

Signals from commensal bacteria can influence immune cell development and susceptibility to infectious or inflammatory diseases. However, the mechanisms by which commensal bacteria regulate protective immunity after exposure to systemic pathogens remain poorly understood. Here, we demonstrate that antibiotic-treated (ABX) mice exhibit impaired innate and adaptive antiviral immune responses and substantially delayed viral clearance after exposure to systemic LCMV or mucosal influenza virus. Furthermore, ABX mice exhibited severe bronchiole epithelial degeneration and increased host mortality after influenza virus infection. Genome-wide transcriptional profiling of macrophages isolated from ABX mice revealed decreased expression of genes associated with antiviral immunity. Moreover, macrophages from ABX mice exhibited defective responses to type I and type II IFNs and impaired capacity to limit viral replication. Collectively, these data indicate that commensal-derived signals provide tonic immune stimulation that establishes the activation threshold of the innateimmune system required for optimal antiviral immunity.

Differences in the ecology ofBartonellainfections ofApodemus flavicollisandMyodes glareolusin a boreal forest

The epidemiology of Bartonella species infecting Apodemus flavicollis and Myodes glareolus in a forest in Eastern Poland was followed for 2 years using mark-recapture. Infections could be acquired in any month, but prevalence, and probability of infection, peaked in the summer. There were significant differences in the pattern of infections between the two species. Both hosts were primarily infected as juveniles, but the probability of infection was highest for A. flavicollis, which, evidence suggests, experienced longer-lasting infections with a wider range of Bartonella genotypes. There was no evidence of increased host mortality associated with Bartonella, although the infection did affect the probability of recapture. Animals could become re-infected, generally by different Bartonella genotypes. Several longer lasting, poorly resolved infections of A. flavicollis involved more than 1 genotype, and may have resulted from sequential infections. Of 22 Bartonella gltA genotypes collected, only 2 (both B. grahamii) were shared between mice and voles; all others were specific either to A. flavicollis or to M. glareolus, and had their nearest relatives infecting Microtus species in neighbouring fields. This heterogeneity in the patterns of Bartonella infections in wild rodents emphasizes the need to consider variation between both, host species and Bartonella genotypes in ecological and epidemiological studies.

Cell-Selective Inhibition of NF-κB Signaling Improves Therapeutic Index in a Melanoma Chemotherapy Model

The transcription factor NF-κB promotes survival of cancer cells exposed to doxorubicin and other chemotherapeutic agents. IκB kinase is essential for chemotherapy-induced NF-κB activation and considered a prime target for anticancer treatment. An IκB kinase inhibitor sensitized human melanoma xenografts in mice to killing by doxorubicin, yet also exacerbated treatment toxicity in the host animals. Using mouse models that simulate cell-selective targeting, we found that impaired NF-κB activation in melanoma and host myeloid cells accounts for the therapeutic and the adverse effects, respectively. Ablation of tumor-intrinsic NF-κB activity resulted in apoptosis-driven tumor regression following doxorubicin treatment. By contrast, chemotherapy in mice with myeloid-specific loss of NF-κB activation led to a massive intratumoral recruitment of interleukin-1β-producing neutrophils and necrotic tumor lesions, a condition associated with increased host mortality but not accompanied by tumor regression. Therefore, a molecular target-based therapy may be steered toward different clinical outcomes depending on the drug's cell-specific effects. Our findings show that the IκB kinase–NF-κB signaling pathway is important for both promoting treatment resistance and preventing host toxicity in cancer chemotherapy; however, the two functions are exerted by distinct cell type–specific mechanisms and can therefore be selectively targeted to achieve an improved therapeutic outcome.

How can immunopathology shape the evolution of parasite virulence?

Immunopathology (immune-mediated pathology) is a ubiquitous cause of disease during infection, but how will parasite exploitation strategies evolve in its presence? Immunopathology can act to increase parasite fitness if it increases transmission rate, but can equally act to decrease parasite fitness if it increases host mortality. The focus here is on understanding how immunopathology, mediated through different immune mechanisms, can influence parasite fitness and how experimental manipulations of the immune system can be carried out to examine this. A better understanding of how parasite fitness scales with, or responds to, immunopathology is crucial to understanding the nature of selection acting on parasite virulence traits and will allow more informed predictions to be made regarding the trajectory of parasite virulence evolution.

Challenges of metamorphosis in invertebrate hosts: maintaining parasite resistance across life‐history stages

1. Insects lack the acquired immune system of vertebrates, but there is some evidence that insect immunity can be primed against an encountered pathogen to mitigate the intensity of future infections within a life stage.2. Many invertebrates have multiple life‐history stages separated by complete metamorphosis, but different life stages can often be infected by the same pathogens, and the potential loss of immune priming during metamorphosis could therefore have detrimental effects on the host. Evidence that invertebrate immune priming can persist through metamorphosis is still missing, and consequently it is unclear how host–parasite interactions change across different life‐history stages in the context of infection history.3. By experimentally manipulating the infection history of the flour beetle Tribolium confusum, we show that intestinal gregarine parasite infections during the larval stage reduced parasite load in adults, demonstrating that a host‐controlled mechanism for parasite resistance can persist through complete metamorphosis in insects.4. Infections reduced larval developmental rates and increased host mortality but only during the crucial metamorphic stage, indicating that parasites impact multiple life stages. In general, our results demonstrate that invertebrates can show surprisingly robust immune priming despite dramatic physiological changes and protect hosts across completely different life‐history stages.

Bacterial Phenotype Variants in Group B Streptococcal Toxic Shock Syndrome1

We conducted genetic and functional analyses of isolates from a patient with group B streptococcal (GBS) necrotizing fasciitis and toxic shock syndrome. Tissue cultures simultaneously showed colonies with high hemolysis (HH) and low hemolysis (LH). Conversely, the HH and LH variants exhibited low capsule (LC) and high capsule (HC) expression, respectively. Molecular analysis demonstrated that the 2 GBS variants were of the same clonal origin. Genetic analysis found a 3-bp deletion in the covR gene of the HH/LC variant. Functionally, this isolate was associated with an increased growth rate in vitro and with higher interleukin-8 induction. However, in whole blood, opsonophagocytic and intracellular killing assays, the LH/HC phenotype demonstrated higher resistance to host phagocytic killing. In a murine model, LH/HC resulted in higher levels of bacteremia and increased host mortality rate. These findings demonstrate differences in GBS isolates of the same clonal origin but varying phenotypes.

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.

Virulence-transmission trade-offs and population divergence in virulence in a naturally occurring butterfly parasite

Why do parasites harm their hosts? Conventional wisdom holds that because parasites depend on their hosts for survival and transmission, they should evolve to become benign, yet many parasites cause harm. Theory predicts that parasites could evolve virulence (i.e., parasite-induced reductions in host fitness) by balancing the transmission benefits of parasite replication with the costs of host death. This idea has led researchers to predict how human interventions-such as vaccines-may alter virulence evolution, yet empirical support is critically lacking. We studied a protozoan parasite of monarch butterflies and found that higher levels of within-host replication resulted in both higher virulence and greater transmission, thus lending support to the idea that selection for parasite transmission can favor parasite genotypes that cause substantial harm. Parasite fitness was maximized at an intermediate level of parasite replication, beyond which the cost of increased host mortality outweighed the benefit of increased transmission. A separate experiment confirmed genetic relationships between parasite replication and virulence, and showed that parasite genotypes from two monarch populations caused different virulence. These results show that selection on parasite transmission can explain why parasites harm their hosts, and suggest that constraints imposed by host ecology can lead to population divergence in parasite virulence.

Host condition as a constraint for parasite reproduction

Environmental stress has been suggested to increase host susceptibility to infections and reduce host ability to resist parasite growth and reproduction, thus benefiting parasites. This prediction stems from expected costs of immune defence; hosts in poor condition should have less resources to be allocated to immune function. However, the alternative hypothesis for response to environmental stress is that hosts in poor condition provide less resources for parasites and/or suffer higher mortality, leading to reduced parasite growth, reproduction and survival. We contrasted these alternative hypotheses in a trematode–snail (Diplostomum spathaceum–Lymnaea stagnalis) system by asking: (1) how host condition affects parasite reproduction (amount and quality of produced transmission stages) and (2) how host condition affects the survival of infected host individuals. We experimentally manipulated host condition by starving the snails, and found that parasites produced fewer and poorer quality transmission stages in stressed hosts. Furthermore, starvation increased snail mortality. These findings indicate that in well‐established trematode infections, reduced ability of immune allocation has no effect on host exploitation by parasites. Instead, deteriorating resources for the snail host can directly limit the amount of resources available for the parasite. This, together with increased host mortality, may have negative effects on parasite populations in the wild.