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Steinel, N.

Publications and source records attributed to Steinel, N..

6 recordsLinked to original sources

Dietary copper exposure decreases splenic MMC coverage but does not cause splenic disorganization or damage.

Exposure to copper, one of the prevalent contaminants in aquatic environments, has wide-ranging adverse immunological effects. However, it is unclear if copper induced immune changes are due to alterations in lymphoid tissues or the result of direct immune cell toxicity. Therefore, to understand the mechanistic action of copper immunomodulation, we utilized an emerging immunotoxicologic model, threespine stickleback fish (Gasterosteus aculeatus). We exposed stickleback fish to dietary copper for a period of 14 days and examined its effect on the spleen, including histopathologic changes in splenic architecture and resident melanomacrophage centers (MMC) populations. We found that dietary copper exposure decreases splenic MMC coverage, suggesting copper is suppressing this phagocyte population. We found no histopathological differences between control and copper groups. Quantification of splenic compartments demonstrated that there is no significant difference in red or white pulp between the control and copper groups, suggesting that reduced MMC coverage is not due to the expansion of other splenic regions. Overall, results from this study suggest that copper toxicity leads to melanomacrophage suppression without damaging or altering the splenic secondary immune tissue structure. Future studies should examine the effect of copper on melanomacrophage viability, development, and function to better understand the mechanism behind MMC reduction. Impact statementThis study demonstrates that dietary copper reduces splenic MMCs but does not cause histopathological damage or alter other compartments of spleen, including the red and white pulp, suggesting that copper-induced immune modulation is the result of direct melanomacrophage toxicity and not due to secondary immune tissue damage. MMC assays could be a useful tool for monitoring heavy metal and other contaminant exposures in aquatic organisms.

immunology↗

Among-population variation in the threespine stickleback ( Gasterosteus aculeatus ) liver metabolome: effects of ancestry and environment

Untargeted metabolomics offers a powerful lens for quantifying high-dimensional phenotypic variation within and among species in nature, but has yet to be widely adopted in evolutionary ecology. Some important initial questions are whether metabolome composition differs among populations, and to what extent such variation is genetic or plastic. Here, we use untargeted liquid chromatography tandem mass spectrometry to characterize the relative abundance of 5,939 molecular features of the threespine stickleback (Gasterosteus aculeatus) liver metabolome. Native lake populations differ in metabolome composition, reflecting effects of sex, size, geography, and population ecotype (benthic versus limnetic). Stickleback from these lakes were translocated to found new populations in nine recently fishless lakes, permuting fish ecotypes across benthic and limnetic lake habitats. Several generations later, metabolomes in these experimental populations reflect effects both of their genetic ancestry (e.g., taurocholic acid, a cholane steroid bile acid, was elevated in limnetic-ancestries), as well as their present habitat (e.g., acylcarnitines). Additionally, ecotypes transplanted into a habitat to which they were maladapted exhibited a distinctive metabolomic profile. We conclude that stickleback exhibit both heritable and plastic among-population differences in liver metabolome, which could represent an important phenotypic basis of rapid evolution, population divergence, and perhaps local adaptation.

Molecular Biology↗

An intestinal cell atlas and organoid model for the threespine stickleback

The intestine plays a crucial role in physiology, nutrition, and immune function, but intestinal anatomy and cell types have yet to be fully characterized in many fish species, the most diverse group of vertebrates. To address this gap, we characterized the structure and composition of the intestine of threespine stickleback (Gasterosteus aculeatus), an emerging model teleost in biological research. Using histology, myeloperoxidase staining, single-cell RNA sequencing, and RNA in situ hybridization, we defined major intestinal epithelial, immune, stromal, and stem/progenitor populations. Goblet cells were abundant in proximal and hindgut, while myeloperoxidase-positive granulocytes were evenly distributed throughout the intestine. To facilitate future experimental studies of stickleback intestinal function, we also developed the first intestinal organoid culture from stickleback and show that these cultures recapitulate epithelial architecture and retain expression of canonical intestinal epithelial markers. This organoid platform enables future functional studies of mucosal immunity, host-microbe interactions, and intestinal physiology in stickleback and related teleosts. Together, our integrated approach provides a comprehensive cell atlas and a novel experimental model for studying digestive and immune functions in threespine stickleback.

Cell Biology↗

Destabilized host-parasite dynamics in newly founded populations

When species disperse into previously unoccupied habitats, new populations encounter unfamiliar species interactions such as altered parasite loads. Theory predicts that newly founded populations should exhibit destabilized eco-evolutionary fluctuations in infection rates and immune traits. However, to understand founder effects biologists typically rely on retrospective studies of range expansions, missing early-generation infection dynamics. To remedy this, we experimentally founded whole-lake populations of threespine stickleback. Infection rates were temporally stable in native source lakes. In contrast, newly founded populations exhibit destabilized host-parasite dynamics: high starting infection rates led to increases in a heritable immune trait (peritoneal fibrosis), suppressing infection rates. The resulting temporal auto-correlation between infection and immunity suggest that newly founded populations can exhibit rapid host-parasite eco-evolutionary dynamics.

evolutionary biology↗

Host sex and genotype modify the gut microbiome response to helminth infection

The microbial community can be altered by direct/indirect interactions with parasites infecting host. Direct interactions can arise from physical/chemical contact with the parasite. Indirect interactions can involve parasite-induced changes in host immunity. If so, this would represent a case of genetic polymorphism in one species controlling an ecological interaction between other species. Here, we report a test of this expectation: we experimentally exposed Gasterosteus aculeatus to their naturally co-evolved parasite, Schistocephalus solidus. The host microbiome differed in response to parasite exposure, and between infected and uninfected fish. The microbial response to infection differed between host sexes, and also varied between variants at autosomal quantitative trait loci (QTL). These results indicate that host genotype regulates the indirect effect of infection on a vertebrate gut microbiome. Our results also raise the possibility that this sex-bias may be related to sex-specific microbial responses to the presence (or, absence) of helminthes. Therefore, helminth-based therapeutics as possible treatments for inflammatory bowel diseases might need to take account of these interactions, potentially requiring therapies tailored to host sex or genotype.

microbiology↗

The role of gene expression in the recent evolution of resistance in a model host parasite system

Damage by parasites is a perpetual challenge for hosts, often leading to the evolution of elaborate mechanisms of avoidance, immunity, or tolerance. Host resistance can evolve via changes in immune protein coding and/or expression. Heritable population differences in gene expression following infection can reveal mechanisms of immune evolution. We compared gene expression in infected and uninfected threespine stickleback (Gasterosteus aculeatus) from two natural populations that differ in their resistance to a native cestode parasite, Schistocephalus solidus. Genes in both the innate and adaptive immune system were differentially expressed as a function of host population, infection status, and their interaction. These genes were enriched for loci controlling immune functions that we independently verified differ between host populations, or in response to infection. For instance, populations differ strongly in reactive oxygen (ROS) production, and we observed corresponding differences in expression of ROS-affecting loci. Differentially expressed genes also were involved in fibroblast activation, B-cell activation, and leukocyte trafficking. Coexpression network analysis identified two distinct immune processes contributing to stickleback resistance; several modules of genes are correlated with parasite survival while a different set of modules are correlated with suppression of cestode growth. Comparison of networks between populations showed resistant fish have a dynamic expression profile while susceptible fish are static. In summary, recent evolutionary divergence between two vertebrate populations has generated population-specific gene expression responses to parasite infection, which reveal a few immune modules likely to separately affect cestode establishment, and growth.

evolutionary biology↗