Host-pathogen Systems Research Articles

Using a Bayesian network to clarify areas requiring research in a host-pathogen system.

Bayesian network analyses can be used to interactively change the strength of effect of variables in a model to explore complex relationships in new ways. In doing so, they allow one to identify influential nodes that are not well studied empirically so that future research can be prioritized. We identified relationships in host and pathogen biology to examine disease-driven declines of amphibians associated with amphibian chytrid fungus (Batrachochytrium dendrobatidis). We constructed a Bayesian network consisting of behavioral, genetic, physiological, and environmental variables that influence disease and used them to predict host population trends. We varied the impacts of specific variables in the model to reveal factors with the most influence on host population trend. The behavior of the nodes (the way in which the variables probabilistically responded to changes in states of the parents, which are the nodes or variables that directly influenced them in the graphical model) was consistent with published results. The frog population had a 49% probability of decline when all states were set at their original values, and this probability increased when body temperatures were cold, the immune system was not suppressing infection, and the ambient environment was conducive to growth of B. dendrobatidis. These findings suggest the construction of our model reflected the complex relationships characteristic of host-pathogen interactions. Changes to climatic variables alone did not strongly influence the probability of population decline, which suggests that climate interacts with other factors such as the capacity of the frog immune system to suppress disease. Changes to the adaptive immune system and disease reservoirs had a large effect on the population trend, but there was little empirical information available for model construction. Our model inputs can be used as a base to examine other systems, and our results show that such analyses are useful tools for reviewing existing literature, identifying links poorly supported by evidence, and understanding complexities in emerging infectious-disease systems.

Impacts of Beech Bark Disease and Climate Change on American Beech

American beech (Fagus grandifolia Ehrh.) is a dominant component of forest tree cover over a large portion of eastern North America and this deciduous, mast-bearing tree species plays a key role in these forest ecosystems. Beech bark disease (BBD) is a scale insect-fungus complex that has caused the decline and death of afflicted beech trees. This disease has become a common feature in North American forest landscapes. Resistance to BBD is at the level of the beech scale (Cryptococcus fagisuga Lind.). Beech scale attack predisposes the tree to subsequent infection by Neonectria fungi. The impact of this tree disease has been shown to be significant, particularly in beech dominated forests. Scale-free trees (resistant to BBD) have been reported to range from only 1% to 3% in infested stands, with estimates ranging from 80–95% for overall infestation (for all beech within the current North American range). In addition to BBD, overall beech health will be directly impacted by climate change, if one specifically considers the expected fluctuations in precipitation leading to both drought periods and flooding. Beech is particularly sensitive to both extremes and is less resilient than other broad leaf tree species. Although the increase in global temperatures will likely shift the current range of the American beech, milder winters and less snowpack will favor propagation and survival of the beech scale. This review aims to present the current outlook for American beech in light of climate change. The natural history of the American beech and the onslaught of BBD during the last century will be covered, followed by the potential effects of a changing climate on BBD-infested forests. Evidence from models of European beech (Fagus sylvatica) and other host-pathogen systems will supplement data directly gathered to evaluate BBD in American beech. We present the case that although climate change is likely to be a confounding factor in the continued loss of American beech, increasing our understanding of possible mechanisms of resistance and environmental factors that may influence susceptibility of American beech to BBD can inform proactive management strategies.

Climate change and human infectious diseases: A synthesis of research findings from global and spatio-temporal perspectives

The life cycles and transmission of most infectious agents are inextricably linked with climate. In spite of a growing level of interest and progress in determining climate change effects on infectious disease, the debate on the potential health outcomes remains polarizing, which is partly attributable to the varying effects of climate change, different types of pathogen-host systems, and spatio-temporal scales. We summarize the published evidence and show that over the past few decades, the reported negative or uncertain responses of infectious diseases to climate change has been growing. A feature of the research tendency is the focus on temperature and insect-borne diseases at the local and decadal scale. Geographically, regions experiencing higher temperature anomalies have been given more research attention; unfortunately, the Earth's most vulnerable regions to climate variability and extreme events have been less studied. From local to global scales, agreements on the response of infectious diseases to climate change tend to converge. So far, an abundance of findings have been based on statistical methods, with the number of mechanistic studies slowly growing. Research gaps and trends identified in this study should be addressed in the future.

Urbanization and the dynamics of RNA viruses in Mallards (Anas platyrhynchos)

Urbanization is intensifying worldwide, and affects the epidemiology of infectious diseases. However, the effect of urbanization on natural host-pathogen systems remains poorly understood. Urban ducks occupy an interesting niche in that they directly interact with both humans and wild migratory birds, and either directly or indirectly with food production birds. Here we have collected samples from Mallards (Anas platyrhynchos) residing in a pond in central Uppsala, Sweden, from January 2013 to January 2014. This artificial pond is kept ice-free during the winter months, and is a popular location where the ducks are fed, resulting in a resident population of ducks year-round. Nine hundred and seventy seven (977) fecal samples were screened for RNA viruses including: influenza A virus (IAV), avian paramyxovirus 1, avian coronavirus (CoV), and avian astrovirus (AstroV). This intra-annual dataset illustrates that these RNA viruses exhibit similar annual patterns to IAV, suggesting similar ecological factors are at play. Furthermore, in comparison to wild ducks, autumnal prevalence of IAV and CoV are lower in this urban population. We also demonstrate that AstroV might be a larger burden to urban ducks than IAV, and should be better assessed to demonstrate the degree to which wild birds contribute to the epidemiology of these viruses. The presence of economically relevant viruses in urban Mallards highlights the importance of elucidating the ecology of wildlife pathogens in urban environments, which will become increasingly important for managing disease risks to wildlife, food production animals, and humans.

Evidence for microbial local adaptation in nature.

Local adaptation is an outcome of divergent selection on microbial populations and has been linked to the immense genetic diversity of microbes observed in nature. Because it is difficult to study microbes in their natural habitats, most tests of microbial local adaptation have been performed in model laboratory systems; as a result, microbiologists have limited understanding of local adaptation among natural microbial populations. In this review, we summarize the evidence for microbial local adaptation in nature. Local adaptation has been most frequently studied, and most frequently found, in host-pathogen systems. We argue that more research is needed to understand the prevalence of local adaptation in free-living microbial populations. However, researchers will need to overcome a variety of logistical and conceptual challenges when studying natural microbial local adaptation, including a lack of solid understanding of many microbes' natural histories. We propose strategies to facilitate future natural history research on divergent selection. We also summarize laboratory experimental work investigating the ecological and evolutionary processes leading to local adaptation. Microbiologists' ongoing challenge is to integrate the valuable knowledge gained from laboratory experiments into well-designed field experiments. Such integration will help us understand the prevalence of, and circumstances leading to, local adaptation among microorganisms.

Modeling Rabbit Responses to Single and Multiple Aerosol Exposures of Bacillus anthracis Spores.

Survival models are developed to predict response and time-to-response for mortality in rabbits following exposures to single or multiple aerosol doses of Bacillus anthracis spores. Hazard function models were developed for a multiple-dose data set to predict the probability of death through specifying functions of dose response and the time between exposure and the time-to-death (TTD). Among the models developed, the best-fitting survival model (baseline model) is an exponential dose-response model with a Weibull TTD distribution. Alternative models assessed use different underlying dose-response functions and use the assumption that, in a multiple-dose scenario, earlier doses affect the hazard functions of each subsequent dose. In addition, published mechanistic models are analyzed and compared with models developed in this article. None of the alternative models that were assessed provided a statistically significant improvement in fit over the baseline model. The general approach utilizes simple empirical data analysis to develop parsimonious models with limited reliance on mechanistic assumptions. The baseline model predicts TTDs consistent with reported results from three independent high-dose rabbit data sets. More accurate survival models depend upon future development of dose-response data sets specifically designed to assess potential multiple-dose effects on response and time-to-response. The process used in this article to develop the best-fitting survival model for exposure of rabbits to multiple aerosol doses of B. anthracis spores should have broad applicability to other host-pathogen systems and dosing schedules because the empirical modeling approach is based upon pathogen-specific empirically-derived parameters.

Species decline under nitrogen fertilization increases community-level competence of fungal diseases.

The artificial fertilization of soils can alter the structure of natural plant communities and exacerbate pathogen emergence and transmission. Although the direct effects of fertilization on disease resistance in plants have received some research attention, its indirect effects of altered community structure on the severity of fungal disease infection remain largely uninvestigated. We designed manipulation experiments in natural assemblages of Tibetan alpine meadow vegetation along a nitrogen-fertilization gradient over 5 years to compare the relative importance of direct and indirect effects of fertilization on foliar fungal infections at the community level. We found that species with lower proneness to pathogens were more likely to be extirpated following fertilization, such that community-level competence of disease, and thus community pathogen load, increased with the intensity of fertilization. The amount of nitrogen added (direct effect) and community disease competence (indirect effect) provided the most parsimonious combination of parameters explaining the variation in disease severity. Our experiment provides a mechanistic explanation for the dilution effect in fertilized, natural assemblages in a highly specific pathogen-host system, and thus insights into the consequences of human ecosystem modifications on the dynamics of infectious diseases.

Environmental Persistence Influences Infection Dynamics for a Butterfly Pathogen

Many pathogens, including those infecting insects, are transmitted via dormant stages shed into the environment, where they must persist until encountering a susceptible host. Understanding how abiotic conditions influence environmental persistence and how these factors influence pathogen spread are crucial for predicting patterns of infection risk. Here, we explored the consequences of environmental transmission for infection dynamics of a debilitating protozoan parasite (Ophryocystis elektroscirrha) that infects monarch butterflies (Danaus plexippus). We first conducted an experiment to observe the persistence of protozoan spores exposed to natural conditions. Experimental results showed that, contrary to our expectations, pathogen doses maintained high infectivity even after 16 days in the environment, although pathogens did yield infections with lower parasite loads after environmental exposure. Because pathogen longevity exceeded the time span of our experiment, we developed a mechanistic model to better explore environmental persistence for this host-pathogen system. Model analysis showed that, in general, longer spore persistence led to higher infection prevalence and slightly smaller monarch population sizes. The model indicated that typical parasite doses shed onto milkweed plants must remain viable for a minimum of 3 weeks for prevalence to increase during the summer-breeding season, and for 11 weeks or longer to match levels of infection commonly reported from the wild, assuming moderate values for parasite shedding rate. Our findings showed that transmission stages of this butterfly pathogen are long-lived and indicated that this is a necessary condition for the protozoan to persist in local monarch populations. This study provides a modeling framework for future work examining the dynamics of an ecologically important pathogen in an iconic insect.

Comparative interactomics for virus-human protein-protein interactions: DNA viruses versus RNA viruses.

Viruses are obligatory intracellular pathogens and completely depend on their hosts for survival and reproduction. The strategies adopted by viruses to exploit host cell processes and to evade host immune systems during infections may differ largely with the type of the viral genetic material. An improved understanding of these viral infection mechanisms is only possible through a better understanding of the pathogen–host interactions (PHIs) that enable viruses to enter into the host cells and manipulate the cellular mechanisms to their own advantage. Experimentally‐verified protein–protein interaction (PPI) data of pathogen–host systems only became available at large scale within the last decade. In this study, we comparatively analyzed the current PHI networks belonging to DNA and RNA viruses and their human host, to get insights into the infection strategies used by these viral groups. We investigated the functional properties of human proteins in the PHI networks, to observe and compare the attack strategies of DNA and RNA viruses. We observed that DNA viruses are able to attack both human cellular and metabolic processes simultaneously during infections. On the other hand, RNA viruses preferentially interact with human proteins functioning in specific cellular processes as well as in intracellular transport and localization within the cell. Observing virus‐targeted human proteins, we propose heterogeneous nuclear ribonucleoproteins and transporter proteins as potential antiviral therapeutic targets. The observed common and specific infection mechanisms in terms of viral strategies to attack human proteins may provide crucial information for further design of broad and specific next‐generation antiviral therapeutics.

Vector-Borne Pathogen and Host Evolution in a Structured Immuno-Epidemiological System.

Vector-borne disease transmission is a common dissemination mode used by many pathogens to spread in a host population. Similar to directly transmitted diseases, the within-host interaction of a vector-borne pathogen and a host's immune system influences the pathogen's transmission potential between hosts via vectors. Yet there are few theoretical studies on virulence-transmission trade-offs and evolution in vector-borne pathogen-host systems. Here, we consider an immuno-epidemiological model that links the within-host dynamics to between-host circulation of a vector-borne disease. On the immunological scale, the model mimics antibody-pathogen dynamics for arbovirus diseases, such as Rift Valley fever and West Nile virus. The within-host dynamics govern transmission and host mortality and recovery in an age-since-infection structured host-vector-borne pathogen epidemic model. By considering multiple pathogen strains and multiple competing host populations differing in their within-host replication rate and immune response parameters, respectively, we derive evolutionary optimization principles for both pathogen and host. Invasion analysis shows that the [Formula: see text] maximization principle holds for the vector-borne pathogen. For the host, we prove that evolution favors minimizing case fatality ratio (CFR). These results are utilized to compute host and pathogen evolutionary trajectories and to determine how model parameters affect evolution outcomes. We find that increasing the vector inoculum size increases the pathogen [Formula: see text], but can either increase or decrease the pathogen virulence (the host CFR), suggesting that vector inoculum size can contribute to virulence of vector-borne diseases in distinct ways.

Pandora formicae, a specialist ant pathogenic fungus: New insights into biology and taxonomy

Among fungi from the order Entomophthorales (Entomophthoromycota), there are many specialized, obligatory insect-killing pathogens. Pandora formicae (Humber & Bałazy) Humber is a rare example of an entomophthoralean fungus adapted to exclusively infect social insects: wood ants from the genus Formica. There is limited information available on P. formicae; many important aspects of this host-pathogen system remain hitherto unknown, and the taxonomical status of the fungus is unclear. Our study fills out some main gaps in the life history of P. formicae, such as seasonal prevalence and overwintering strategy. Field studies of infection prevalence show a disease peak in late summer and early autumn. Typical thick-walled entomophthoralean resting spores of P. formicae are documented and described for the first time. The proportion of cadavers with resting spores increased from late summer throughout autumn, suggesting that these spores are the main overwintering fungal structures. In addition, the phylogenetic status of Pandora formicae is outlined. Finally, we review the available taxonomical literature and conclude that the name P. formicae should be used rather than the name P. myrmecophaga for ant-infecting fungi displaying described morphological features.

Tick-born encephalitis risk assessment based on satellite data

Tick-borne encephalitis (TBE) belongs among the dangerous vector-borne diseases. The number of TBE incidences has been permanently increasing in various geographical regions, including the Czech Republic. The presence of ticks and related diseases is driven by host-pathogen systems. The systems are rather complex and susceptible to environmental conditions represented in the first place by land cover/land use categories. The presented study looks for a possible relation between the types of forest vegetation specified in the Landsat 5 satellite data and relative TBE morbidity. First, supervised classification of forest areas into five vegetation classes predefined by a botanist was tested. Due to the spectral similarity of the classes, the resulting classification accuracy of Landsat scenes covering the entire area of the Czech Republic was quite low. Thus, an unsupervised approach was applied using nine spectral classes. Relative TBE morbidity data collected over 10 years for 206 administrative units covering the entire country presented field data that were correlated with the spectral classes. The TBE risk index (IRE) of a given spectral class was introduced at each satellite scene. To create a map of the TBE risk for the entire country, all IRE values were accumulated and divided into six risk categories. The disadvantages of the proposed method, especially regarding the accuracy of the final product with a nationwide cover age, are discussed. In addition, the correlation between the relative TBE morbidity and other environmental parameters, such as annual precipitation, average temperature, and number of hunted game were calculated, but they did not reveal any significant relationship.

Relevance of Indirect Transmission for Wildlife Disease Surveillance.

Epidemiological models of infectious diseases are essential tools in support of risk assessment, surveillance design, and contingency planning in public and animal health. Direct pathogen transmission from host to host is an essential process of each host–pathogen system and respective epidemiological modeling concepts. It is widely accepted that numerous diseases involve indirect transmission (IT) through pathogens shed by infectious hosts to their environment. However, epidemiological models largely do not represent pathogen persistence outside the host explicitly. We hypothesize that this simplification might bias management-related model predictions for disease agents that can persist outside their host for a certain time span. We adapted an individual-based, spatially explicit epidemiological model that can mimic both transmission processes. One version explicitly simulated indirect pathogen transmission through a contaminated environment. The second version simulated direct host-to-host transmission only. We aligned the model variants by the transmission potential per infectious host (i.e., basic reproductive number R0) and the spatial transmission kernel of the infection to allow unbiased comparison of predictions. The quantitative model results are provided for the example of surveillance plans for early detection of foot-and-mouth disease in wild boar, a social host. We applied systematic sampling strategies on the serological status of randomly selected host individuals in both models. We compared between the model variants the time to detection and the area affected prior to detection, measures that strongly influence mitigation costs. Moreover, the ideal sampling strategy to detect the infection in a given time frame was compared between both models. We found the simplified, direct transmission model to underestimate necessary sample size by up to one order of magnitude but to overestimate the area put under control measures. Thus, the model predictions underestimated surveillance efforts but overestimated mitigation costs. We discuss parameterization of IT models and related knowledge gaps. We conclude that the explicit incorporation of IT mechanisms in epidemiological modeling may reward by adapting surveillance and mitigation efforts.

Secretomic Analysis of Host-Pathogen Interactions Reveals That Elongation Factor-Tu Is a Potential Adherence Factor of Helicobacter pylori during Pathogenesis.

The secreted proteins of bacteria are usually accompanied by virulence factors, which can cause inflammation and damage host cells. Identifying the secretomes arising from the interactions of bacteria and host cells could therefore increase understanding of the mechanisms during initial pathogenesis. The present study used a host-pathogen coculture system of Helicobacter pylori and monocytes (THP-1 cells) to investigate the secreted proteins associated with initial H. pylori pathogenesis. The secreted proteins from the conditioned media from H. pylori, THP-1 cells, and the coculture were collected and analyzed using SDS-PAGE and LC-MS/MS. Results indicated the presence of 15 overexpressed bands in the coculture. Thirty-one proteins were identified-11 were derived from THP-1 cells and 20 were derived from H. pylori. A potential adherence factor from H. pylori, elongation factor-Tu (EF-Tu), was selected for investigation of its biological function. Results from confocal microscopic and flow cytometric analyses indicated the contribution of EF-Tu to the binding ability of H. pylori in THP-1. The data demonstrated that fluorescence of EF-Tu on THP-1 cells increased after the addition of the H. pylori-conditioned medium. This study reports a novel secretory adherence factor in H. pylori, EF-Tu, and further elucidates mechanisms of H. pylori adaptation for host-pathogen interaction during pathogenesis.

The genetic basis of local adaptation for pathogenic fungi in agricultural ecosystems.

Local adaptation plays a key role in the evolutionary trajectory of host-pathogen interactions. However, the genetic architecture of local adaptation in host-pathogen systems is poorly understood. Fungal plant pathogens in agricultural ecosystems provide highly tractable models to quantify phenotypes and map traits to corresponding genomic loci. The outcome of crop-pathogen interactions is thought to be governed largely by gene-for-gene interactions. However, recent studies showed that virulence can be governed by quantitative trait loci and that many abiotic factors contribute to the outcome of the interaction. After introducing concepts of local adaptation and presenting examples from wild plant pathosystems, we focus this review on a major pathogen of wheat, Zymoseptoria tritici, to show how a multitude of traits can affect local adaptation. Zymoseptoria tritici adapted to different thermal environments across its distribution range, indicating that thermal adaptation may limit effective dispersal to different climates. The application of fungicides led to the rapid evolution of multiple, independent resistant populations. The degree of colony melanization showed strong pleiotropic effects with other traits, including trade-offs with colony growth rates and fungicide sensitivity. The success of the pathogen on its host can be assessed quantitatively by counting pathogen reproductive structures and measuring host damage based on necrotic lesions. Interestingly, these two traits can be weakly correlated and depend both on host and pathogen genotypes. Quantitative trait mapping studies showed that the genetic architecture of locally adapted traits varies from single loci with large effects to many loci with small individual effects. We discuss how local adaptation could hinder or accelerate the development of epidemics in agricultural ecosystems.

Manipulating virulence factor availability can have complex consequences for infections.

Given the rise of bacterial resistance against antibiotics, we urgently need alternative strategies to fight infections. Some propose we should disarm rather than kill bacteria, through targeted disruption of their virulence factors. It is assumed that this approach (i) induces weak selection for resistance because it should only minimally impact bacterial fitness, and (ii) is specific, only interfering with the virulence factor in question. Given that pathogenicity emerges from complex interactions between pathogens, hosts and their environment, such assumptions may be unrealistic. To address this issue in a test case, we conducted experiments with the opportunistic human pathogen Pseudomonas aeruginosa, where we manipulated the availability of a virulence factor, the iron‐scavenging pyoverdine, within the insect host Galleria mellonella. We observed that pyoverdine availability was not stringently predictive of virulence and affected bacterial fitness in nonlinear ways. We show that this complexity could partly arise because pyoverdine availability affects host responses and alters the expression of regulatorily linked virulence factors. Our results reveal that virulence factor manipulation feeds back on pathogen and host behaviour, which in turn affects virulence. Our findings highlight that realizing effective and evolutionarily robust antivirulence therapies will ultimately require deeper engagement with the intrinsic complexity of host–pathogen systems.

Distinct immune responses and virus shedding in pigs following aerosol, intra-nasal and contact infection with pandemic swine influenza A virus, A(H1N1)09.

Influenza virus infection in pigs is a major farming problem, causing considerable economic loss and posing a zoonotic threat. In addition the pig is an excellent model for understanding immunity to influenza viruses as this is a natural host pathogen system. Experimentally, influenza virus is delivered to pigs intra-nasally, by intra-tracheal instillation or by aerosol, but there is little data comparing the outcome of different methods. We evaluated the shedding pattern, cytokine responses in nasal swabs and immune responses following delivery of low or high dose swine influenza pdmH1N1 virus to the respiratory tract of pigs intra-nasally or by aerosol and compared them to those induced in naturally infected contact pigs. Our data shows that natural infection by contact induces remarkably high innate and adaptive immune response, although the animals were exposed to a very low virus dose. In contacts, the kinetics of virus shedding were slow and prolonged and more similar to the low dose directly infected animals. In contrast the cytokine profile in nasal swabs, antibody and cellular immune responses of contacts more closely resemble immune responses in high dose directly inoculated animals. Consideration of these differences is important for studies of disease pathogenesis and assessment of vaccine protective efficacy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13567-016-0390-5) contains supplementary material, which is available to authorized users.

A natural Anopheles-associated Penicillium chrysogenum enhances mosquito susceptibility to Plasmodium infection.

Whereas studies have extensively examined the ability of bacteria to influence Plasmodium infection in the mosquito, the tripartite interactions between non-entomopathogenic fungi, mosquitoes, and Plasmodium parasites remain largely uncharacterized. Here we report the isolation of a common mosquito-associated ascomycete fungus, Penicillium chrysogenum, from the midgut of field-caught Anopheles mosquitoes. Although the presence of Pe. chrysogenum in the Anopheles gambiae midgut does not affect mosquito survival, it renders the mosquito significantly more susceptible to Plasmodium infection through a secreted heat-stable factor. We further provide evidence that the mechanism of the fungus-mediated modulation of mosquito susceptibility to Plasmodium involves an upregulation of the insect’s ornithine decarboxylase gene, which sequesters arginine for polyamine biosynthesis. Arginine plays an important role in the mosquito’s anti-Plasmodium defense as a substrate of nitric oxide production, and its availability therefore has a direct impact on the mosquito’s susceptibility to the parasite. While this type of immunomodulatory mechanism has already been demonstrated in other host-pathogen interaction systems, this is the first report of a mosquito-associated fungus that can suppress the mosquito’s innate immune system in a way that would favor Plasmodium infection and possibly malaria transmission.

Aging promotes acquisition of naive-like CD8+ memory T cell traits and enhanced functionalities.

Protective T cell memory is an acquired trait that is contingent upon the preservation of its constituents and therefore vulnerable to the potentially deleterious effects of organismal aging. Here, however, we have found that long-term T cell memory in a natural murine host-pathogen system can substantially improve over time. Comprehensive molecular, phenotypic, and functional profiling of aging antiviral CD8+ memory T cells (CD8+ TM) revealed a pervasive remodeling process that promotes the gradual acquisition of distinct molecular signatures, of increasingly homogeneous phenotypes, and of diversified functionalities that combine to confer a CD8+ TM-autonomous capacity for enhanced recall responses and immune protection. Notably, the process of CD8+ TM aging is characterized by a progressive harmonization of memory and naive T cell traits, is broadly amenable to experimental acceleration or retardation, and serves as a constitutional component for the "rebound model" of memory T cell maturation. By casting CD8+ TM populations within the temporal framework of their slowly evolving properties, this model establishes a simple ontogenetic perspective on the principal organization of CD8+ T cell memory that may directly inform the development of improved diagnostic, prophylactic, and therapeutic modalities.

Do not feed the wildlife: associations between garbage use, aggression, and disease in banded mongooses (Mungos mungo).

SummaryUrbanization and other human modifications of the landscape may indirectly affect disease dynamics by altering host behavior in ways that influence pathogen transmission. Few opportunities arise to investigate behaviorally mediated effects of human habitat modification in natural host–pathogen systems, but we provide a potential example of this phenomenon in banded mongooses (Mungos mungo), a social mammal. Our banded mongoose study population in Botswana is endemically infected with a novel Mycobacterium tuberculosis complex pathogen, M. mungi, that primarily invades the mongoose host through the nasal planum and breaks in the skin. In this system, several study troops have access to human garbage sites and other modified landscapes for foraging. Banded mongooses in our study site (N = 4 troops, ~130 individuals) had significantly higher within‐troop aggression levels when foraging in garbage compared to other foraging habitats. Second, monthly rates of aggression were a significant predictor of monthly number of injuries in troops. Finally, injured individuals had a 75% incidence of clinical tuberculosis (TB) compared to a 0% incidence in visibly uninjured mongooses during the study period. Our data suggest that mongoose troops that forage in garbage may be at greater risk of acquiring TB by incurring injuries that may allow for pathogen invasion. Our study suggests the need to consider the indirect effects of garbage on behavior and wildlife health when developing waste management approaches in human‐modified areas.