RESUMO
Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by the same pathogen can 'prime' the immune response, resulting in improved survival upon reinfection. Here, we investigated the mechanistic basis and epidemiological consequences of innate immune priming in the fruit fly Drosophila melanogaster when infected with the gram-negative bacterial pathogen Providencia rettgeri. We find that priming in response to P. rettgeri infection is a long-lasting and sexually dimorphic response. We further explore the epidemiological consequences of immune priming and find it has the potential to curtail pathogen transmission by reducing pathogen shedding and spread. The enhanced survival of individuals previously exposed to a non-lethal bacterial inoculum coincided with a transient decrease in bacterial loads, and we provide strong evidence that the effect of priming requires the IMD-responsive antimicrobial-peptide Diptericin-B in the fat body. Further, we show that while Diptericin B is the main effector of bacterial clearance, it is not sufficient for immune priming, which requires regulation of IMD by peptidoglycan recognition proteins. This work underscores the plasticity and complexity of invertebrate responses to infection, providing novel experimental evidence for the effects of innate immune priming on population-level epidemiological outcomes.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Imunidade Inata , Providencia , Animais , Drosophila melanogaster/microbiologia , Drosophila melanogaster/imunologia , Providencia/imunologia , Proteínas de Drosophila/imunologia , Feminino , Masculino , Infecções por Enterobacteriaceae/imunologia , Infecções por Enterobacteriaceae/transmissão , Peptídeos AntimicrobianosRESUMO
BACKGROUND: Mitochondria participate in various cellular processes including energy metabolism, apoptosis, autophagy, production of reactive oxygen species, stress responses, inflammation and immunity. However, the role of mitochondrial metabolism in immune cells and tissues shaping the innate immune responses are not yet fully understood. We investigated the effects of tissue-specific mitochondrial perturbation on the immune responses at the organismal level. Genes for oxidative phosphorylation (OXPHOS) complexes cI-cV were knocked down in the fruit fly Drosophila melanogaster, targeting the two main immune tissues, the fat body and the immune cells (hemocytes). RESULTS: While OXPHOS perturbation in the fat body was detrimental, hemocyte-specific perturbation led to an enhanced immunocompetence. This was accompanied by the formation of melanized hemocyte aggregates (melanotic nodules), a sign of activation of cell-mediated innate immunity. Furthermore, the hemocyte-specific OXPHOS perturbation induced immune activation of hemocytes, resulting in an infection-like hemocyte profile and an enhanced immune response against parasitoid wasp infection. In addition, OXPHOS perturbation in hemocytes resulted in mitochondrial membrane depolarization and upregulation of genes associated with the mitochondrial unfolded protein response. CONCLUSIONS: Overall, we show that while the effects of mitochondrial perturbation on immune responses are highly tissue-specific, mild mitochondrial dysfunction can be beneficial in immune-challenged individuals and contributes to variation in infection outcomes among individuals.
Assuntos
Drosophila , Vespas , Animais , Humanos , Drosophila melanogaster/metabolismo , Vespas/genética , Mitocôndrias , Imunidade Inata , Hemócitos/metabolismoRESUMO
Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation between life span and the proportion of time cybrids spent moving while alive. Our results suggest that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.
Assuntos
Drosophila melanogaster , Mitocôndrias , Animais , Feminino , Drosophila melanogaster/fisiologia , Mitocôndrias/genética , Longevidade/genética , Genótipo , Fertilidade/genéticaRESUMO
Organismal health and survival depend on the ability to mount an effective immune response against infection. Yet immune defence may be energy-demanding, resulting in fitness costs if investment in immune function deprives other physiological processes of resources. While evidence of costly immunity resulting in reduced longevity and reproduction is common, the role of energy-producing mitochondria on the magnitude of these costs is unknown. Here, we employed Drosophila melanogaster cybrid lines, where several mitochondrial genotypes (mitotypes) were introgressed onto a single nuclear genetic background, to explicitly test the role of mitochondrial variation on the costs of immune stimulation. We exposed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen (stimulating immune deployment while avoiding pathology) or to a sterile control and measured lifespan, fecundity, and locomotor activity. We observed mitotype-specific costs of immune stimulation and identified a positive genetic correlation in immune-stimulated flies between lifespan and the proportion of time cybrids spent moving while alive. Our results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.
Assuntos
Drosophila melanogaster , Longevidade , Mitocôndrias , Animais , Drosophila melanogaster/imunologia , Drosophila melanogaster/genética , Drosophila melanogaster/microbiologia , Feminino , Mitocôndrias/genética , FertilidadeRESUMO
Host heterogeneity in disease transmission is widespread but precisely how different host traits drive this heterogeneity remains poorly understood. Part of the difficulty in linking individual variation to population-scale outcomes is that individual hosts can differ on multiple behavioral, physiological and immunological axes, which will together impact their transmission potential. Moreover, we lack well-characterized, empirical systems that enable the quantification of individual variation in key host traits, while also characterizing genetic or sex-based sources of such variation. Here we used Drosophila melanogaster and Drosophila C Virus as a host-pathogen model system to dissect the genetic and sex-specific sources of variation in multiple host traits that are central to pathogen transmission. Our findings show complex interactions between genetic background, sex, and female mating status accounting for a substantial proportion of variance in lifespan following infection, viral load, virus shedding, and viral load at death. Two notable findings include the interaction between genetic background and sex accounting for nearly 20% of the variance in viral load, and genetic background alone accounting for ~10% of the variance in viral shedding and in lifespan following infection. To understand how variation in these traits could generate heterogeneity in individual pathogen transmission potential, we combined measures of lifespan following infection, virus shedding, and previously published data on fly social aggregation. We found that the interaction between genetic background and sex explained ~12% of the variance in individual transmission potential. Our results highlight the importance of characterising the sources of variation in multiple host traits to understand the drivers of heterogeneity in disease transmission.
Assuntos
Drosophila melanogaster/genética , Drosophila melanogaster/virologia , Interações Hospedeiro-Patógeno , Vírus de Insetos/patogenicidade , Carga Viral , Eliminação de Partículas Virais , Animais , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Longevidade , Masculino , Fatores SexuaisRESUMO
The insect gut is frequently exposed to pathogenic threats and must not only clear these potential infections, but also tolerate relatively high microbe loads. In contrast to the mechanisms that eliminate pathogens, we currently know less about the mechanisms of disease tolerance. We investigated how well-described mechanisms that prevent, signal, control or repair damage during infection contribute to the phenotype of disease tolerance. We established enteric infections with the bacterial pathogen Pseudomonas entomophila in transgenic lines of Drosophila melanogaster fruit flies affecting dcy (a major component of the peritrophic matrix), upd3 (a cytokine-like molecule), irc (a negative regulator of reactive oxygen species) and egfr1 (epithelial growth factor receptor). Flies lacking dcy experienced the highest mortality, while loss of function of either irc or upd3 reduced tolerance in both sexes. The disruption of egfr1 resulted in a severe loss in tolerance in male flies but had no substantial effect on the ability of female flies to tolerate P. entomophila infection, despite carrying greater microbe loads than males. Together, our findings provide evidence for the role of damage limitation mechanisms in disease tolerance and highlight how sexual dimorphism in these mechanisms could generate sex differences in infection outcomes.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Bactérias/metabolismo , Drosophila , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/fisiologia , Receptores ErbB , Feminino , MasculinoRESUMO
Evolutionary theory predicts a late-life decline in the force of natural selection, possibly leading to late-life deregulations of the immune system. A potential outcome of such deregulations is the inability to produce specific immunity against target pathogens. We tested this possibility by infecting multiple Drosophila melanogaster lines (with bacterial pathogens) across age groups, where either individual or different combinations of Imd- and Toll-inducible antimicrobial peptides (AMPs) were deleted using CRISPR gene editing. We show a high degree of non-redundancy and pathogen-specificity of AMPs in young flies: in some cases, even a single AMP could confer complete resistance. However, ageing led to drastic reductions in such specificity to target pathogens, warranting the action of multiple AMPs across Imd and Toll pathways. Moreover, use of diverse AMPs either lacked survival benefits or even accompanied survival costs post-infection. These features were also sexually dimorphic: females required a larger repertoire of AMPs than males but extracted equivalent survival benefits. Finally, age-specific expansion of the AMP-repertoire was accompanied with ageing-induced downregulation of negative-regulators of the Imd pathway and damage to renal function post-infection, as features of poorly regulated immunity. Overall, we could highlight the potentially non-adaptive role of ageing in producing less-specific AMP responses, across sexes and pathogens.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Animais , Feminino , Masculino , Envelhecimento , Peptídeos Catiônicos Antimicrobianos/genética , Peptídeos Antimicrobianos , Drosophila melanogaster/genética , Imunidade InataRESUMO
Mitochondria are organelles that produce cellular energy in the form of ATP through oxidative phosphorylation, and this primary function is conserved among many taxa. Locomotion is a trait that is highly reliant on metabolic function and expected to be greatly affected by disruptions to mitochondrial performance. To this end, we aimed to examine how activity and sleep vary between Drosophila melanogaster strains with different geographic origins, how these patterns are affected by mitochondrial DNA (mtDNA) variation, and how breaking up co-evolved mito-nuclear gene combinations affect the studied activity traits. Our results demonstrate that Drosophila strains from different locations differ in sleep and activity, and that females are generally more active than males. By comparing activity and sleep of mtDNA variants introgressed onto a common nuclear background in cytoplasmic hybrid (cybrid) strains, we were able to quantify the among-line variance attributable to mitochondrial DNA, and we establish that mtDNA variation affects both activity and sleep, in a sex-specific manner. Altogether our study highlights the important role that mitochondrial genome variation plays on organismal physiology and behaviour.
Assuntos
DNA Mitocondrial , Drosophila melanogaster , Trifosfato de Adenosina/metabolismo , Animais , DNA Mitocondrial/genética , Drosophila/genética , Drosophila melanogaster/genética , Feminino , Locomoção/genética , Masculino , Mitocôndrias/genética , Sono/genéticaRESUMO
Identifying how infection modifies host behaviours that determine social contact networks is important for understanding heterogeneity in infectious disease dynamics. Here, we investigate whether group social behaviour is modified during bacterial infection in fruit flies (Drosophila melanogaster) according to pathogen species, infectious dose, host genetic background and sex. In one experiment, we find that systemic infection with four different bacterial species results in a reduction in the mean pairwise distance within infected female flies, and that the extent of this change depends on pathogen species. However, susceptible flies did not show any evidence of avoidance in the presence of infected flies. In a separate experiment, we observed genetic- and sex-based variation in social aggregation within infected, same-sex groups, with infected female flies aggregating more closely than infected males. In general, our results confirm that bacterial infection induces changes in fruit fly behaviour across a range of pathogen species, but also highlight that these effects vary between fly genetic backgrounds and can be sex-specific. We discuss possible explanations for sex differences in social aggregation and their consequences for individual variation in pathogen transmission.
Assuntos
Infecções Bacterianas , Drosophila melanogaster , Animais , Drosophila , Drosophila melanogaster/genética , Feminino , Masculino , Comportamento SocialRESUMO
Host heterogeneity in pathogen transmission is widespread and presents a major hurdle to predicting and minimizing disease outbreaks. Using Drosophila melanogaster infected with Drosophila C virus as a model system, we integrated experimental measurements of social aggregation, virus shedding, and disease-induced mortality from different genetic lines and sexes into a disease modelling framework. The experimentally measured host heterogeneity produced substantial differences in simulated disease outbreaks, providing evidence for genetic and sex-specific effects on disease dynamics at a population level. While this was true for homogeneous populations of single sex/genetic line, the genetic background or sex of the index case did not alter outbreak dynamics in simulated, heterogeneous populations. Finally, to explore the relative effects of social aggregation, viral shedding and mortality, we compared simulations where we allowed these traits to vary, as measured experimentally, to simulations where we constrained variation in these traits to the population mean. In this context, variation in infectiousness, followed by social aggregation, was the most influential component of transmission. Overall, we show that host heterogeneity in three host traits dramatically affects population-level transmission, but the relative impact of this variation depends on both the susceptible population diversity and the distribution of population-level variation.
Assuntos
Surtos de Doenças , Drosophila melanogaster/virologia , Dinâmica Populacional , Animais , Genótipo , Fatores SexuaisRESUMO
When future reproductive potential is threatened, for example following infection, the terminal investment hypothesis predicts that individuals will respond by investing preferentially in current reproduction. Terminal investment involves reallocating resources to current reproductive effort, so it is likely to be influenced by the quantity and quality of resources acquired through diet. Dietary protein specifically has been shown to impact both immunity and reproduction in a range of organisms, but its impact on terminal investment is unclear. We challenged females from ten naturally derived fruit fly (Drosophila melanogaster) genotypes with the bacterial pathogen Pseudomonas aeruginosa. We then placed these on either a standard or isocaloric high-protein diet, and measured multiple components of reproductive investment. As oogenesis requires protein, and flies increase egg production with protein intake, we hypothesized that terminal investment would be easier to observe if protein was not already limiting. Oral exposure to the pathogen triggered an increase in reproductive investment. However, whereas flies feeding on a high-protein diet increased the number of eggs laid when exposed to P. aeruginosa, those fed the standard diet did not increase the number of eggs laid but increased egg-to-adult viability following infection. This suggests that the specific routes through which flies terminally invest are influenced by the protein content of the maternal diet. We discuss the importance of considering diet and natural routes of infection when measuring nonimmunological defences.
Assuntos
Dieta , Proteínas Alimentares/imunologia , Drosophila melanogaster/imunologia , Animais , Drosophila melanogaster/genética , Drosophila melanogaster/microbiologia , Feminino , Oogênese/fisiologia , Pseudomonas aeruginosa/fisiologia , Análise de SobrevidaRESUMO
Host behavioural changes following infection are common and could be important determinants of host behavioural competence to transmit pathogens. Identifying potential sources of variation in sickness behaviours is therefore central to our understanding of disease transmission. Here, we test how group social aggregation and individual locomotor activity vary between different genotypes of male and female fruit flies (Drosophila melanogaster) following septic infection with Drosophila C virus (DCV). We find genetic-based variation in both locomotor activity and social aggregation, but we did not detect an effect of DCV infection on fly activity or sleep patterns within the initial days following infection. However, DCV infection caused sex-specific effects on social aggregation, as male flies in most genetic backgrounds increased the distance to their nearest neighbour when infected. We discuss possible causes for these differences in the context of individual variation in immunity and their potential consequences for disease transmission.
Assuntos
Drosophila melanogaster , Viroses , Animais , Drosophila , Feminino , Locomoção , Masculino , Comportamento SocialRESUMO
Bacterial symbionts are widespread among metazoans and provide a range of beneficial functions. Wolbachia-mediated protection against viral infection has been extensively demonstrated in Drosophila. In mosquitoes that are artificially transinfected with Drosophila melanogaster Wolbachia (wMel), protection from both viral and bacterial infections has been demonstrated. However, no evidence for Wolbachia-mediated antibacterial protection has been demonstrated in Drosophila to date. Here, we show that the route of infection is key for Wolbachia-mediated antibacterial protection. Drosophila melanogaster carrying Wolbachia showed reduced mortality during enteric-but not systemic-infection with the opportunist pathogen Pseudomonas aeruginosaWolbachia-mediated protection was more pronounced in male flies and is associated with increased early expression of the antimicrobial peptide Attacin A, and also increased expression of a reactive oxygen species detoxification gene (Gst D8). These results highlight that the route of infection is important for symbiont-mediated protection from infection, that Wolbachia can protect hosts by eliciting a combination of resistance and disease tolerance mechanisms, and that these effects are sexually dimorphic. We discuss the importance of using ecologically relevant routes of infection to gain a better understanding of symbiont-mediated protection.
Assuntos
Infecções Bacterianas/microbiologia , Drosophila melanogaster/microbiologia , Simbiose , Wolbachia/fisiologia , Animais , Resistência à Doença , Proteínas de Drosophila/fisiologia , MasculinoRESUMO
The distinction between pathogen elimination and damage limitation during infection is beginning to change perspectives on infectious disease control, and has recently led to the development of novel therapies that focus on reducing the illness caused by pathogens (''damage limitation'')rather than reducing pathogen burdens directly (''pathogen elimination''). While beneficial at the individual host level, the population consequences of these interventions remain unclear. To address this issue,we present a simple conceptual framework for damage limitation during infection that distinguishes between therapies that are either host-centric (pro-tolerance) or pathogen-centric (anti-virulence). We then draw on recent developments from the evolutionary ecology of disease tolerance to highlight some potential epidemiological and evolutionary responses of pathogens to medical interventions that target the symptoms of infection. Just as pathogens are known to evolve in response to antimicrobial and vaccination therapies, we caution that claims of ''evolution-proof'' anti-virulence interventions may be premature, and further, that in infections where virulence and transmission are linked, reducing illness without reducing pathogen burden could have non-trivial epidemiological and evolutionary consequences that require careful examination.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Drogas em Investigação/uso terapêutico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Modelos Estatísticos , Carga Viral/efeitos dos fármacos , Viroses/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêutico , Aspirina/uso terapêutico , Aderência Bacteriana/efeitos dos fármacos , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Toxinas Bacterianas/antagonistas & inibidores , Toxinas Bacterianas/biossíntese , Evolução Biológica , Contagem de Colônia Microbiana , Humanos , Ibuprofeno/uso terapêutico , Tolerância Imunológica/efeitos dos fármacos , Percepção de Quorum/efeitos dos fármacos , Percepção de Quorum/fisiologia , Virulência/efeitos dos fármacos , Fatores de Virulência/antagonistas & inibidores , Fatores de Virulência/biossíntese , Viroses/imunologia , Viroses/virologiaRESUMO
Variation in individual-level disease transmission is well documented, but the underlying causes of this variation are challenging to disentangle in natural epidemics. In general, within-host replication is critical in determining the extent to which infected hosts shed transmission propagules, but which factors cause variation in this relationship are poorly understood. Here, using a plant host, Plantago lanceolata, and the powdery mildew fungus Podosphaera plantaginis, we quantify how the distinct stages of within-host spread (autoinfection), spore release, and successful transmission to new hosts (alloinfection) are influenced by host genotype, pathogen genotype, and the coinfection status of the host. We find that within-host spread alone fails to predict transmission rates, as this relationship is modified by genetic variation in hosts and pathogens. Their contributions change throughout the course of the epidemic. Host genotype and coinfection had particularly pronounced effects on the dynamics of spore release from infected hosts. Confidently predicting disease spread from local levels of individual transmission, therefore, requires a more nuanced understanding of genotype-specific infection outcomes. This knowledge is key to better understanding the drivers of epidemiological dynamics and the resulting evolutionary trajectories of infectious disease.
Assuntos
Ascomicetos/genética , Coinfecção , Doenças das Plantas/genética , Plantago/genética , Plantago/microbiologia , Ascomicetos/fisiologia , Coinfecção/microbiologia , Doenças Transmissíveis/microbiologia , Doenças Transmissíveis/transmissão , Variação Genética , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/microbiologia , Esporos Fúngicos/fisiologiaRESUMO
CRISPR-Cas is a form of adaptive sequence-specific immunity in microbes. This system offers unique opportunities for the study of coevolution between bacteria and their viral pathogens, bacteriophages. A full understanding of the coevolutionary dynamics of CRISPR-Cas requires knowing the magnitude of the cost of resisting infection. Here, using the gram-positive bacterium Streptococcus thermophilus and its associated virulent phage 2972, a well-established model system harbouring at least two type II functional CRISPR-Cas systems, we obtained different fitness measures based on growth assays in isolation or in pairwise competition. We measured the fitness cost associated with different components of this adaptive immune system: the cost of Cas protein expression, the constitutive cost of increasing immune memory through additional spacers, and the conditional costs of immunity during phage exposure. We found that Cas protein expression is particularly costly, as Cas-deficient mutants achieved higher competitive abilities than the wild-type strain with functional Cas proteins. Increasing immune memory by acquiring up to four phage-derived spacers was not associated with fitness costs. In addition, the activation of the CRISPR-Cas system during phage exposure induces significant but small fitness costs. Together these results suggest that the costs of the CRISPR-Cas system arise mainly due to the maintenance of the defence system. We discuss the implications of these results for the evolution of CRISPR-Cas-mediated immunity.
Assuntos
Imunidade Adaptativa , Bacteriófagos/fisiologia , Sistemas CRISPR-Cas , Streptococcus thermophilus/fisiologia , Streptococcus thermophilus/virologia , Evolução Molecular , Aptidão Genética , Memória Imunológica , Streptococcus thermophilus/genética , Streptococcus thermophilus/imunologiaRESUMO
The environmental conditions experienced by hosts are known to affect their mean parasite transmission potential. How different conditions may affect the variance of transmission potential has received less attention, but is an important question for disease management, especially if specific ecological contexts are more likely to foster a few extremely infectious hosts. Using the obligate-killing bacterium Pasteuria ramosa and its crustacean host Daphnia magna, we analysed how host nutrition affected the variance of individual parasite loads, and, therefore, transmission potential. Under low food, individual parasite loads showed similar mean and variance, following a Poisson distribution. By contrast, among well-nourished hosts, parasite loads were right-skewed and overdispersed, following a negative binomial distribution. Abundant food may, therefore, yield individuals causing potentially more transmission than the population average. Measuring both the mean and variance of individual parasite loads in controlled experimental infections may offer a useful way of revealing risk factors for potential highly infectious hosts.
Assuntos
Daphnia/microbiologia , Infecções por Bactérias Gram-Positivas/transmissão , Estado Nutricional/fisiologia , Pasteuria/patogenicidade , Animais , Carga Bacteriana , Distribuição Binomial , Chlorella vulgaris/fisiologia , Daphnia/fisiologia , Feminino , Alimentos , Interações Hospedeiro-Parasita , Funções Verossimilhança , Distribuição de Poisson , Esporos Bacterianos/patogenicidadeRESUMO
Disease tolerance describes an infected host's ability to maintain health independently of the ability to clear microbe loads. The Jak/Stat pathway plays a pivotal role in humoral innate immunity by detecting tissue damage and triggering cellular renewal, making it a candidate tolerance mechanism. Here, we find that in Drosophila melanogaster infected with Pseudomonas entomophila disrupting ROS-producing dual oxidase (duox) or the negative regulator of Jak/Stat Socs36E, render male flies less tolerant. Another negative regulator of Jak/Stat, G9a - which has previously been associated with variable tolerance of viral infections - did not affect the rate of mortality with increasing microbe loads compared to flies with functional G9a, suggesting it does not affect tolerance of bacterial infection as in viral infection. Our findings highlight that ROS production and Jak/Stat signalling influence the ability of flies to tolerate bacterial infection sex-specifically and may therefore contribute to sexually dimorphic infection outcomes in Drosophila.
Assuntos
Proteínas de Drosophila , Drosophila , Masculino , Animais , Drosophila melanogaster , Transdução de Sinais , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Janus Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição STAT/metabolismoRESUMO
Genetic variation for resistance and disease tolerance has been described in a range of species. In Drosophila melanogaster, genetic variation in mortality following systemic Drosophila C virus (DCV) infection is driven by large-effect polymorphisms in the restriction factor pastrel (pst). However, it is unclear if pst contributes to disease tolerance. We investigated systemic DCV challenges spanning nine orders of magnitude, in males and females of 10 Drosophila Genetic Reference Panel lines carrying either a susceptible (S) or resistant (R) pst allele. We find among-line variation in fly survival, viral load and disease tolerance measured both as the ability to maintain survival (mortality tolerance) and reproduction (fecundity tolerance). We further uncover novel effects of pst on host vigour, as flies carrying the R allele exhibited higher survival and fecundity even in the absence of infection. Finally, we found significant genetic variation in the expression of the JAK-STAT ligand upd3 and the epigenetic regulator of JAK-STAT G9a. However, while G9a has been previously shown to mediate tolerance of DCV infection, we found no correlation between the expression of either upd3 or G9a on fly tolerance or resistance. Our work highlights the importance of both resistance and tolerance in viral defence.
Assuntos
Drosophila melanogaster , Drosophila , Feminino , Masculino , Animais , Carga Viral , Drosophila melanogaster/genética , Alelos , Polimorfismo GenéticoRESUMO
Epidemiology in host meta-populations depends on parasite ability to disperse between, establish and persist in distinct sub-populations of hosts. We studied the genetic factors determining the short-term establishment, and long-term maintenance, of pathogens introduced by infected hosts (i.e. carriers) into recipient populations. We used experimental populations of the freshwater ciliate Paramecium caudatum and its bacterial parasite Holospora undulata. Parasite short-term spread (approximately one horizontal transmission cycle) was affected mainly by carrier genotype, and its interactions with parasite and recipient genotypes. By contrast, parasite longer term spread (2-3 horizontal transmission cycles) was mostly determined by parasite isolate. Importantly, measures of parasite short-term success (reproductive number, R) were not good predictors for longer term prevalence, probably because of the specific interactions between host and parasite genotypes. Analogous to variation in vectorial capacity and super-spreader occurrence, two crucial components of epidemiology, we show that carrier genotype can also affect disease spread within meta-populations.