Laboratory mice have provided invaluable insight into mammalian immune systems. Yet the immune phenotypes of mice bred and maintained in conventional laboratory conditions often differ from the ...immune phenotypes of wild mammals. Recent work to naturalize the environmental experience of inbred laboratory mice-to take them where the wild things are (to borrow a phrase from Maurice Sendak), via approaches such as construction of exposure histories, provision of fecal transplants or surrogate mothering by wild mice, and rewilding-is poised to expand understanding, complementing genetic and phylogenetic research on how natural selection has shaped mammalian immune systems while improving the translational potential of mouse research.
Coinfection of a host by multiple parasite species has important epidemiological and clinical implications. However, the direction and magnitude of effects vary considerably among systems, and, until ...now, there has been no general framework within which to explain this variation. Community ecology has great potential for application to such problems in biomedicine. Here, metaanalysis of data from 54 experiments on laboratory mice reveals that basic ecological rules govern the outcome of coinfection across a broad spectrum of parasite taxa. Specifically, resource-based ("bottom-up") and predator-based ("top-down") control mechanisms combined to determine microparasite population size in helminth-coinfected hosts. Coinfection imposed bottom-up control (resulting in decreased microparasite density) when a helminth that causes anemia was paired with a microparasite species that requires host red blood cells. At the same time, coinfection impaired top-down control of microparasites by the immune system: the greater the helminth-induced suppression of the inflammatory cytokine interferon (IFN)-γ, the greater the increase in microparasite density. These results suggest that microparasite population growth will be most explosive when underlying helminths do not impose resource limitations but do strongly modulate IFN-γ responses. Surprisingly simple rules and an ecological framework within which to analyze biomedical data thus emerge from analysis of this dataset. Through such an interdisciplinary lens, predicting the outcome of coinfection may become tractable.
serosim is an open-source R package designed to aid inference from serological studies, by simulating data arising from user-specified vaccine and antibody kinetics processes using a random effects ...model. Serological data are used to assess population immunity by directly measuring individuals' antibody titers. They uncover locations and/or populations which are susceptible and provide evidence of past infection or vaccination to help inform public health measures and surveillance. Both serological data and new analytical techniques used to interpret them are increasingly widespread. This creates a need for tools to simulate serological studies and the processes underlying observed titer values, as this will enable researchers to identify best practices for serological study design, and provide a standardized framework to evaluate the performance of different inference methods. serosim allows users to specify and adjust model inputs representing underlying processes responsible for generating the observed titer values like time-varying patterns of infection and vaccination, population demography, immunity and antibody kinetics, and serological sampling design in order to best represent the population and disease system(s) of interest. This package will be useful for planning sampling design of future serological studies, understanding determinants of observed serological data, and validating the accuracy and power of new statistical methods.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mimulus guttatus and M. nasutus are an evolutionary and ecological model sister species pair differentiated by ecology, mating system, and partial reproductive isolation. Despite extensive research ...on this system, the history of divergence and differentiation in this sister pair is unclear. We present and analyze a population genomic data set which shows that M. nasutus budded from a central Californian M. guttatus population within the last 200 to 500 thousand years. In this time, the M. nasutus genome has accrued genomic signatures of the transition to predominant selfing, including an elevated proportion of nonsynonymous variants, an accumulation of premature stop codons, and extended levels of linkage disequilibrium. Despite clear biological differentiation, we document genomic signatures of ongoing, bidirectional introgression. We observe a negative relationship between the recombination rate and divergence between M. nasutus and sympatric M. guttatus samples, suggesting that selection acts against M. nasutus ancestry in M. guttatus.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Plant biologists have long recognized that host defence against parasites and pathogens can be divided into two conceptually different components: the ability to limit parasite burden (resistance) ...and the ability to limit the harm caused by a given burden (tolerance). Together these two components determine how well a host is protected against the effects of parasitism. This distinction is useful because it recognizes that hosts that are best at controlling parasite burdens are not necessarily the healthiest. Moreover, resistance and tolerance can be expected to have different effects on the epidemiology of infectious diseases and host-parasite coevolution. However, studies of defence in animals have to date focused on resistance, whereas the possibility of tolerance and its implications have been largely overlooked. The aim of our review is to (i) describe the statistical framework for analysis of tolerance developed in plant science and how this can be applied to animals, (ii) review evidence of genetic and environmental variation for tolerance in animals, and studies indicating which mechanisms could contribute to this variation, and (iii) outline avenues for future research on this topic.
Given vaccine dose shortages and logistical challenges, various deployment strategies are being proposed to increase population immunity levels to severe acute respiratory syndrome coronavirus 2 ...(SARS-CoV-2). Two critical issues arise: How timing of delivery of the second dose will affect infection dynamics and how it will affect prospects for the evolution of viral immune escape via a buildup of partially immune individuals. Both hinge on the robustness of the immune response elicited by a single dose as compared with natural and two-dose immunity. Building on an existing immuno-epidemiological model, we find that in the short term, focusing on one dose generally decreases infections, but that longer-term outcomes depend on this relative immune robustness. We then explore three scenarios of selection and find that a one-dose policy may increase the potential for antigenic evolution under certain conditions of partial population immunity. We highlight the critical need to test viral loads and quantify immune responses after one vaccine dose and to ramp up vaccination efforts globally.
The vertebrate gut teems with a large, diverse, and dynamic bacterial community that has pervasive effects on gut physiology, metabolism, and immunity. Under natural conditions, these microbes share ...their habitat with a similarly dynamic community of eukaryotes (helminths, protozoa, and fungi), many of which are well-known parasites. Both parasites and the prokaryotic microbiota can dramatically alter the physical and immune landscape of the gut, creating ample opportunities for them to interact. Such interactions may critically alter infection outcomes and affect overall host health and disease. For instance, parasite infection can change how a host interacts with its bacterial flora, either driving or protecting against dysbiosis and inflammatory disease. Conversely, the microbiota can alter a parasite's colonization success, replication, and virulence, shifting it along the parasitism-mutualism spectrum. The mechanisms and consequences of these interactions are just starting to be elucidated in an emergent transdisciplinary area at the boundary of microbiology and parasitology. However, heterogeneity in experimental designs, host and parasite species, and a largely phenomenological and taxonomic approach to synthesizing the literature have meant that common themes across studies remain elusive. Here, we use an ecological perspective to review the literature on interactions between the prokaryotic microbiota and eukaryotic parasites in the vertebrate gut. Using knowledge about parasite biology and ecology, we discuss mechanisms by which they may interact with gut microbes, the consequences of such interactions for host health, and how understanding parasite-microbiota interactions may lead to novel approaches in disease control.
Zoonotic spillover, which is the transmission of a pathogen from a vertebrate animal to a human, presents a global public health burden but is a poorly understood phenomenon. Zoonotic spillover ...requires several factors to align, including the ecological, epidemiological and behavioural determinants of pathogen exposure, and the within-human factors that affect susceptibility to infection. In this Opinion article, we propose a synthetic framework for animal-to-human transmission that integrates the relevant mechanisms. This framework reveals that all zoonotic pathogens must overcome a hierarchical series of barriers to cause spillover infections in humans. Understanding how these barriers are functionally and quantitatively linked, and how they interact in space and time, will substantially improve our ability to predict or prevent spillover events. This work provides a foundation for transdisciplinary investigation of spillover and synthetic theory on zoonotic transmission.
Genetic and environmental factors shape host susceptibility to infection, but how and how rapidly environmental variation might alter the susceptibility of mammalian genotypes remains unknown. Here, ...we investigate the impacts of seminatural environments upon the nematode susceptibility profiles of inbred C57BL/6 mice. We hypothesized that natural exposure to microbes might directly (e.g., via trophic interactions) or indirectly (e.g., via microbe-induced immune responses) alter the hatching, growth, and survival of nematodes in mice housed outdoors. We found that while C57BL/6 mice are resistant to high doses of nematode (Trichuris muris) eggs under clean laboratory conditions, exposure to outdoor environments significantly increased their susceptibility to infection, as evidenced by increased worm burdens and worm biomass. Indeed, mice kept outdoors harbored as many worms as signal transducer and activator of transcription 6 (STAT6) knockout mice, which are genetically deficient in the type 2 immune response essential for clearing nematodes. Using 16S ribosomal RNA sequencing of fecal samples, we discovered enhanced microbial diversity and specific bacterial taxa predictive of nematode burden in outdoor mice. We also observed decreased type 2 and increased type 1 immune responses in lamina propria and mesenteric lymph node (MLN) cells from infected mice residing outdoors. Importantly, in our experimental design, different groups of mice received nematode eggs either before or after moving outdoors. This contrasting timing of rewilding revealed that enhanced hatching of worms was not sufficient to explain the increased worm burdens; instead, microbial enhancement and type 1 immune facilitation of worm growth and survival, as hypothesized, were also necessary to explain our results. These findings demonstrate that environment can rapidly and significantly shape gut microbial communities and mucosal responses to nematode infections, leading to variation in parasite expulsion rates among genetically similar hosts.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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