Biology subjects

Graham, A. L.

Publications and source records attributed to Graham, A. L..

9 recordsLinked to original sources

bioRxiv2024

Density-dependent network structuring within and across wild animal systems

High population density should drive individuals to more frequently share space and interact, producing better-connected spatial and social networks [1-4]. Although this theory is fundamental to our understanding of disease dynamics [2,5-8], it remains unconfirmed how local density generally drives individuals positions within their networks, which reduces our ability to understand and predict density-dependent processes [4,9,10]. Here we provide the first general evidence that density drives greater network connectedness at fine spatiotemporal scales, at the scale of individuals within wild animal populations. We analysed 36 datasets of simultaneous spatial and social behaviour in >58,000 individual animals, spanning 30 species of fish, reptiles, birds, mammals, and insects. 80% of systems exhibited strong positive relationships between local density and network centrality. However, >80% of relationships were nonlinear and 75% became shallower at higher values, signifying that demographic and behavioural processes counteract densitys effects, thereby producing saturating trends [11-15]. Densitys effect was much stronger and less saturating for spatial than social networks, such that individuals become disproportionately spatially connected rather than socially at higher densities. Consequently, ecological processes that depend on spatial connections (e.g. indirect pathogen transmission, resource competition, and territory formation) are likely more density-dependent than those involving social interactions (e.g. direct pathogen transmission, aggression, and social learning). These findings reveal fundamental ecological rules governing societal structuring, with widespread implications. Identifying scaling rules based on processes that generalise across systems, such as these patterns of density dependence, might provide the ability to predict network structures in novel systems.

ecology↗

bioRxiv2023

Dose-dependent interaction of parasites with tiers of host defence generates "wormholes" that prolong infection at intermediate inoculum sizes

Immune responses are induced by parasite exposure and can in turn reduce parasite burden. Despite such apparently simple rules of engagement, key drivers of within-host dynamics, including dose-dependence of defence and infection duration, have proven difficult to predict. Here, we model how varied inoculating doses interact with host defences. Defence is multi-tiered, with 3 tiers invoked for all animals: barrier, innate, and adaptive. We model how these tiers interact with replicating and non-replicating parasites across six orders of magnitude of dose. We find that, in general, intermediate parasite doses generate infections of longest duration because they are sufficient in number to breach barrier defences, but insufficient to strongly induce subsequent tiers of defence. Deviation from the hypothesis of independent action, which postulates that each parasite has an independent probability of establishing infection, may therefore be widespread. Most interestingly, our model predicts local maxima of duration at two doses - one for each tier transition. While empirical evidence is consistent with nonlinear dose-dependencies, the profiles with multiple turning points that we predict will require finer-scale dose experiments than are usually undertaken. Our results help explain varied infection duration among differentially-exposed hosts and elucidate evolutionary pressures that shape both virulence and defence.

ecology↗

bioRxiv2023

Social association predicts immunological similarity in rewilded mice

Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individuals interaction with its environment. We tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including social associations, to immune phenotypes. We found that the more associated two individuals were, the more similar their immune phenotypes were. Social association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or worm infection status. These results highlight the importance of social networks for immune phenotype and reveal important immunological correlates of social life.

immunology↗

bioRxiv2022

Natural helminth infections reduce relative abundance of inflammation-inducing Prevotella in wild primates

Microbes living within the mammalian gastrointestinal tract affect the metabolization and extraction of dietary nutrients, immune function, colonization by pathogens, and risk of autoimmune disease. While most microbiome studies focus on sequences of the 16S gene shared by Bacteria and Archaea, these are not the only regular inhabitants of mammalian guts. Macroparasites such as helminths are nearly ubiquitous in wildlife, and a quarter of the worlds human population harbors helminths; these worms affect host physiology as they compete with microbiota over host resources while also affecting host immunity, and changing the host microbiome. Little is understood about how helminths interact with microbiomes to affect host disease states, and few studies have examined these interactions in natural systems in genetically diverse hosts experiencing coinfections and other stressors. We surveyed the microbiomes and helminth parasites of wild primates and found strong associations between helminths and microbes in the bacterial microbiome. Notably, we find that the presence of a strongyle we hypothesize to be hookworm is correlated strongly with decreased relative abundance of Prevotella species, a lineage associated with inflammatory bowel disease humans. This observed decline in Prevotella relative abundance, a genus implicated in several host autoimmune and inflammatory disorders, motivates future research on whether the mixed results of helminthic therapy (i.e., "infecting" patients with gastrointestinal nematodes to treat various diseases) stem from the mixed causes of inflammation, and whether inflammation specifically correlated with Prevotella-driven dysbiosis can be mediated through mechanisms mimicking how hookworms and other nematodes behave in the gastrointestinal ecosystem of their hosts. Our findings lend ground-truthed support to previous lab-based studies and limited/restricted human trials showing potential benefits, via microbial modulation, of nematode therapy in treating inflammatory bowel disease. Our study adds statistical weight to a link between helminths and a specific lineage of microbes associated with inflammation.

ecology↗

bioRxiv2021

Optimal immune specificity at the intersection of host life history and parasite epidemiology

Epidemiology and life history are commonly hypothesized to influence host immune strategy, and the pairwise relationships between immune strategy and each factor have been extensively investigated. But the interaction of these two is rarely considered, despite evidence that this interaction might produce emergent effects on optimal immune strategy. Here we investigate the confluence of epidemiology and life history as it affects immune strategy through a demographically-framed model of sensitivity and specificity in parasite recognition and response. We find that variation in several different life history traits associated with both reproduction and longevity alters optimal immune strategies - but the direction and magnitude of these effects depends on how epidemiological risks vary across life. Drawing on published life history data, we also find that our predictions apply across chordate taxa. Our results shed light on the complex interactions shaping immune strategy and may prove valuable in interpreting empirical results in ecoimmunology.

ecology↗

bioRxiv2020

Experimental parasite community perturbation reveals associations between Sin Nombre virus and gastrointestinal nematodes in a rodent reservoir host

Individuals are often co-infected with several parasite species, yet measuring within-host interactions remains difficult in the wild. Consequently, such interactions impacts on host fitness and epidemiology are often unknown. We used anthelmintic drugs to experimentally reduce nematode infection and measured the effects on both nematodes and the important zoonosis Sin Nombre virus (SNV) in its primary wild reservoir (Peromyscus spp.). Treatment significantly reduced nematode infection, but increased SNV seroprevalence. Furthermore, mice that were co-infected with both nematodes and SNV were in better condition and survived as much as four times longer than mice infected with either parasite alone. These results highlight the importance of investigating multiple parasites for understanding interindividual variation and epidemiological dynamics in reservoir populations with zoonotic transmission potential.

ecology↗

bioRxiv2019

Housing laboratory mice in a natural environment uncovers genetic and environmental contributions to immune variation.

The relative contributions of genetic and environmental factors to variation in immune responses are still poorly understood. Here, we performed a deep phenotypic analysis of immunological parameters of laboratory mice released into an outdoor enclosure, carrying susceptibility genes (Nod2 and Atg16l1) implicated in the development of inflammatory bowel diseases. Variations of immune cell populations were largely driven by environment, whereas cytokine production in response to stimulation was affected more by genetic mutations. Multi-omic models identified transcriptional signatures associated with differences in T cell populations. Subnetworks associated with responses against Clostridium perfringens, Candida albicans and Bacteroides vulgatus were also coupled with rewilding. Hence, exposing laboratory mice carrying different genetic mutations to a natural environment uncovered important contributors to immune variation. One sentence summaryNatural environment exposure in laboratory mice primarily promotes variation in population frequencies of immune cells, whereas cytokine responses to stimulation are affected more by genetic susceptibility to inflammatory bowel disease.

immunology↗

bioRxiv2019

Altered immunity of laboratory mice in the natural environment is associated with fungal colonization

The immune systems of free-living mammals such as humans and wild mice display a heightened degree of activation compared with laboratory mice maintained under artificial conditions. Here, we demonstrate that releasing inbred laboratory mice into an outdoor enclosure to mimic life in a natural environment alters the state of immunity. In addition to enhancing the differentiation of T cell populations previously associated with pathogen exposure, we found that outdoor release of mice led to an increase in circulating granulocytes. However, rewilded mice were not infected by pathogens previously implicated in immune activation. Rather, changes to the immune system were associated with an altered composition of the microbiota, and fungi isolated from rewilded mice were sufficient to increase circulating granulocytes. These findings establish an experimental procedure to investigate the impact of the natural environment on immune development and identify a role for sustained fungal exposure in determining granulocyte numbers.

immunology↗

bioRxiv2019

Within-host dynamics of virulent viruses in bat reservoirs for emerging zoonotic disease

Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-replicating viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.

ecology↗