Find research datasets worth reusing

opencc-by-4.0Jan 2021View details →

Characterization of the microbiome and immune response in corals with chronic Montipora white syndrome.

Complete code and data files for the Motipora White Syndrome paper. Run in Qiime2 2020.11, mostly on the command line.

opencc-zeroApr 2020View details →

Data from: Male rock lizards may compensate reproductive costs of an immune challenge affecting sexual signals

Sexual signals can be evolutionarily stable if they are condition dependent or costly to the signaler. One of these costs may be the trade-off between maintaining the immune system and the elaboration of ornaments. Experimental immune challenges in captivity show a reduction in the expression of sexual signals, but it is not clear whether these detrimental effects are important in nature and, more importantly, whether they have reproductive consequences. We designed a field experiment to challenge the immune system of wild male Carpetan rock lizards, Iberolacerta cyreni, with a bacterial antigen (LPS). The immune challenge decreased relative reflectance of UV structural and melanin-dependent sexual coloration in the throat and the lateral ocelli, whereas the carotenoid-dependent dorsal green coloration was not affected. Immune activation also decreased proportions of ergosterol and cholesta-5,7-dien-3-ol in femoral secretions. These results support a trade-off between the immune system and both visual and chemical sexual ornaments. Moreover, reproductive success of males, estimated with DNA microsatellites, depended on the expression of some color and chemical traits. However, the immune challenge did not cause overall differences in reproductive success, although it increased with body size/age in control but not in challenged males. This suggests the use of alternative reproductive strategies (e.g. forced matings) in challenged males, particularly in smaller ones. These males might consider that their survival probabilities are low and increase reproductive effort as a form of terminal investment in spite of their "low-quality" sexual signals and potential survival costs.

opencc-zeroMar 2020View details →

Experimental facilitation of heat loss affects work rate and innate immune function in a breeding passerine bird

The capacity to get rid of excess heat produced during hard work is a possible constraint on parental effort during reproduction (heat dissipation limit [HDL] theory). We released hard-working blue tits (Cyanistes caeruleus) from this constraint by experimentally removing ventral plumage. We then assessed if this changed their reproductive effort (feeding rate and nestling size) and levels of self-maintenance (change in body mass and innate immune function). Feather-clipped females reduced the number of feeding visits and increased levels of constitutive innate immunity compared to unclipped females but did not fledge smaller nestlings. Thus, they increased self-maintenance without compromising current reproductive output. In contrast, feather-clipping did not affect the number of feeding visits or innate immune function in males, despite increased heat loss rate. Our results show that analyses of physiological parameters, such as constitutive innate immune function, can be important when trying to understand sources of variation in investment in self-maintenance versus reproductive effort and that risk of overheating can influence innate immune function during reproduction.

opencc-zeroDec 2017View details →

Data from: Microevolutionary selection dynamics acting on immune genes of the green veined white butterfly, Pieris napi

Insects rely on their innate immune system to successfully mediate complex interactions with their microbiota, as well as the microbes present in the environment. Previous work has shown that components of the canonical immune gene repertoire evolve rapidly and have evolutionary characteristics originating from interactions with fast-evolving microorganisms. Although these interactions are likely to vary among populations, there is a poor understanding of the microevolutionary dynamics of immune genes, especially in non-Dipteran insects. Here we use the full set of canonical insect immune genes to investigate microevolutionary dynamics acting on these genes between and among populations by comparing three allopatric populations of the Green Veined White butterfly, Pieris napi (Lepidoptera, Pieridae). Immune genes showed increased genetic diversity compared to genes from the rest of the genome and various functional categories exhibited different types of signatures of selection, at different evolutionary scales, presenting a complex pattern of selection dynamics. Signatures of balancing selection were identified in 10 genes, and 17 genes appear to be under positive selection. Genes involved with the cellular arm of the immune response as well as the Toll pathway appear to be enriched among our outlier loci, regardless of functional category. This suggests that the targets of selection might focus upon an entire pathway, more than on functional subsets across pathways. Our microevolutionary results are similar to previously observed macroevolutionary patterns from diverse taxa, suggesting that either the immune system is robust to dramatic differences in life history and microbial communities, or that diverse microbes exert similar selection pressures.

opencc-zeroFeb 2020View details →

Immunization with full-length Plasmodium falciparum merozoite surface protein 1 is safe and elicits functional cytophilic antibodies in a randomized first-in-human trial

This file contains the original data underpinning the article in npj vaccines, in which we describe a phase 1 safety and immunogenicty study on the malaria vaccine candidate MSP1 in humans. The abstract of the article follows: A vaccine remains a priority in the global fight against malaria. Here, we report on a single-center, randomized, double-blind, placebo and adjuvant-controlled, dose escalation phase 1a safety and immunogenicity clinical trial of full-length Plasmodium falciparum merozoite surface protein 1 (MSP1) in combination with GLA-SE adjuvant. 32 healthy volunteers were vaccinated at least three times with MSP1 plus adjuvant, adjuvant alone or placebo (24:4:4) to evaluate the safety and immunogenicity. MSP1 was safe, well tolerated and immunogenic, with all vaccinees sero-converting independent of the dose. The MSP1-specific IgG and IgM titers persisted above levels found in malaria semi-immune humans for at least six months after the last immunization. The antibodies were variant- and strain-transcending and stimulated respiratory activity in granulocytes. Furthermore, full-length MSP1 induced memory T-cells. Our findings encourage challenge studies as the next step to evaluate the efficacy of full-length MSP1 as a vaccine candidate against falciparum malaria (EudraCT 2016-002463-33).

opencc-zeroSep 2019View details →

Data from: Immune stability predicts tuberculosis infection risk in a wild mammal

Immunity is one of the most variable phenotypic traits in animals; however, some individuals may show less fluctuation in immune traits, resulting in stable patterns of immune variation over time. It is currently unknown whether immune variation has consequences for infectious disease risk. In this study, we identified moderately stable immune traits in wild African buffalo and asked whether the stability of these traits affected bovine tuberculosis (TB) infection risk. We found that adaptive immune traits such as the level of IFN-γ released after white blood cell stimulation, the number of circulating lymphocytes, and the level of antibodies against bovine adenovirus-3 were moderately repeatable (i.e. stable) over time, whereas parameters related to innate immunity either had low repeatability (circulating eosinophil numbers) or were not repeatable (e.g. neutrophil numbers, plasma bacteria killing capacity). Intriguingly, individuals with more repeatable IFN-γ and lymphocyte levels were at a significantly higher risk of acquiring TB infection. In stark contrast, average IFN-γ and lymphocyte levels were poor predictors of TB risk, indicating that immune variability rather than absolute response level better captured variation in disease susceptibility. This work highlights the important and under-appreciated role of immune variability as a predictor of infection risk.

opencc-zeroNov 2019View details →

Comparing raccoon MHC diversity in native and introduced ranges: evidence for the importance of functional immune diversity for adaptation and survival in novel environments.

The adaptive potential of invasive species is related to the genetic diversity of the invader, which is influenced by genetic drift and natural selection. Typically, the genetic diversity of invaders is studied with neutral genetic markers, however, the expectation of reduced diversity has not been consistently supported by empirical studies. Here, we describe and interpret genetic diversity at both neutral microsatellite loci and the immune related MHC-DRB locus of native and invasive populations of raccoon to better understand of how drift and selection impact patterns of genetic diversity during the invasion process. We found that despite the loss of many MHC alleles in comparison with native populations, functional MHC supertypes are preserved in the invasive region. In the native raccoon population the number of supertypes within individuals was higher than expected under a neutral model. The high level of individual functional divergence may facilitate the adaptation to local conditions in the invasive range. These results suggest that selection is driving divergent allele combinations despite drift causing allelic loss. In the invasive populations, we also detected increased population structure at microsatellites compared to the MHC locus, further suggesting that balancing selection is acting on adaptively important regions of the raccoon genome. Finally, we found that alleles known to exhibit resistance to rabies in the native range, Prlo-DRB*4, Prlo-DRB*16 and Prlo-DRB*102, were the most common alleles in the European populations, suggesting directional selection is acting on this locus. Our research shows empirical support for the importance of functional immune diversity for adaptation and survival in novel environments.

opencc-zeroDec 2016View details →

Data from: Experimental evolution of insect immune memory versus pathogen resistance

Under strong pathogen pressure, insects often evolve resistance to infection. Many insects are also protected via immune memory ('immune priming'), whereby sub-lethal exposure to a pathogen enhances survival after secondary infection. Theory predicts that immune memory should evolve when the pathogen is highly virulent, or when pathogen exposure is relatively rare. However, there are no empirical tests of these hypotheses, and the adaptive benefits of immune memory relative to direct resistance against a pathogen are poorly understood. To determine the selective pressures and ecological conditions that shape immune evolution, we imposed strong pathogen selection on flour beetle (Tribolium castaneum) populations, infecting them with Bacillus thuringiensis (Bt) for 11 generations. Populations injected first with heat-killed and then live Bt each generation evolved high basal resistance against multiple Bt strains. In contrast, populations injected only with a high dose of live Bt evolved a less effective but strain-specific priming response. Control populations injected with heat-killed Bt did not evolve priming; and in the ancestor, priming was effective only against a low Bt dose. Intriguingly, one replicate population first evolved priming and subsequently evolved basal resistance, suggesting the potential for dynamic evolution of different immune strategies. Our work is the first report showing that pathogens can select for rapid modulation of insect priming ability, allowing hosts to evolve divergent immune strategies (generalized resistance vs. specific immune memory) with potentially distinct mechanisms.

opencc-zeroDec 2016View details →

Data from: Drought and immunity determine the intensity of West Nile virus epidemics and climate change impacts

The effect of global climate change on infectious disease remains hotly debated because multiple extrinsic and intrinsic drivers interact to influence transmission dynamics in nonlinear ways. The dominant drivers of widespread pathogens, like West Nile virus, can be challenging to identify due to regional variability in vector and host ecology, with past studies producing disparate findings. Here, we used analyses at national and state scales to examine a suite of climatic and intrinsic drivers of continental-scale West Nile virus epidemics, including an empirically derived mechanistic relationship between temperature and transmission potential that accounts for spatial variability in vectors. We found that drought was the primary climatic driver of increased West Nile virus epidemics, rather than within-season or winter temperatures, or precipitation independently. Local-scale data from one region suggested drought increased epidemics via changes in mosquito infection prevalence rather than mosquito abundance. In addition, human acquired immunity following regional epidemics limited subsequent transmission in many states. We show that over the next 30 years, increased drought severity from climate change could triple West Nile virus cases, but only in regions with low human immunity. These results illustrate how changes in drought severity can alter the transmission dynamics of vector-borne diseases.

opencc-zeroDec 2017View details →

Data from: Incomplete host immunity favors the evolution of virulence in an emergent pathogen

Immune memory evolved to protect hosts from reinfection, but incomplete responses that allow future reinfection might inadvertently select for more harmful pathogens. We present empirical and modeling evidence that incomplete immunity promotes the evolution of higher virulence in a natural host-pathogen system. We performed sequential infections of house finches with Mycoplasma gallisepticum strains of varying virulence. Virulent bacterial strains generated stronger host protection against reinfection than less virulent strains, and thus excluded less virulent strains from infecting previously-exposed hosts. In a two-strain model, the resulting fitness advantage selected for an almost two-fold increase in pathogen virulence. Thus, the same immune systems that protect hosts from infection can concomitantly drive the evolution of more harmful pathogens in nature.

opencc-zeroDec 2016View details →

Data from: Costs of immunity and their role in the range expansion of the house sparrow in Kenya

There are at least two reasons to study traits that mediate successful range expansions. First, dispersers will found new populations and thus impact the distribution and evolution of species. Second, organisms moving into new areas will influence the fate of resident communities, directly competing with or indirectly affecting residents by spreading non-native or spilling-back native parasites. The success of invaders in new areas is likely mediated by a counterbalancing of costly traits. In new areas where threats are comparatively rare, individuals that grow rapidly and breed prolifically should be at an advantage. High investment in defenses should thus be disfavored. In the present study, we compared the energetic, nutritional and collateral damage costs of an inflammatory response among Kenyan house sparrow (Passer domesticus) populations of different ages, asking whether costs were related to traits of individuals from three different capture sites. Kenya is among the world's most recent range expansions for this species, and we recently found that the expression of Toll-like receptors (TLRs), leukocyte receptors that instigate inflammatory responses when bound to microbial elements, was related to the range expansion across the country. Here, we found (contrary to our expectations) that energetic and nutritional costs of inflammation were higher, but damage costs were lower, in range-edge compared with core birds. Moreover, at the individual level, TLR-4 expression was negatively related to commodity costs (energy and a critical amino acid) of inflammation. Our data thus suggest that costs of inflammation, perhaps mediated by TLR expression, might mitigate successful range expansions.

opencc-zeroJun 2019View details →

Data from: Risk alleles for tuberculosis infection associate with reduced immune reactivity in a wild mammalian host

Integrating biological processes across scales remains a central challenge in disease ecology. Genetic variation drives differences in host immune responses, which, along with environmental factors, generates temporal and spatial infection patterns in natural populations that epidemiologists seek to predict and control. However, genetics and immunology are typically studied in model systems, whereas population-level patterns of infection status and susceptibility are uniquely observable in nature. Despite obvious causal connections, organizational scales from genes to host outcomes to population patterns are rarely linked explicitly. Here we identify two loci near genes involved in macrophage (phagocyte) activation and pathogen degradation that additively increase risk of bovine tuberculosis infection by up to 9-fold in wild African buffalo. Furthermore, we observe genotype-specific variation in IL-12 production indicative of variation in macrophage activation. Here we provide measurable differences in infection resistance at multiple scales by characterizing the genetic and inflammatory variation driving patterns of infection in a wild mammal.

opencc-by-4.0Jul 2024View details →

PINK1 deficiency rewires early immune responses in a mouse model of Parkinson's disease triggered by intestinal infection

Parkinson’s disease is characterized by a period of non-motor symptoms, including gastrointestinal dysfunction, preceding motor deficits by decades. This long prodrome is suggestive of peripheral immunity involvement in the initiation of disease. We previously developed a model system in PINK1 KO mice displaying PD-like motor symptoms at late stages following intestinal infections. Herein, we map the initiating immune events at the site of infection in this model. Using single-cell RNAseq, we demonstrate that peripheral myeloid cells are the earliest highly dysregulated immune cell type in PINK1 KO infected mice followed by an aberrant T cell response shortly after. We elucidate an increased propensity for antigen presentation mediated by myeloid-CD8+ T cell interaction. PINK1 KO activated myeloid cells acquire a proinflammatory profile inducing cytotoxic T cell responses. Together, our study provides the first evidence that PINK1 is a key regulator of immune functions in the gut underlying early PD-related disease mechanisms.

Identification of immune-related candidate biomarkers in plasma of patients with sporadic vestibular schwannoma

Vestibular schwannoma (VS) is an intracranial tumor arising from neoplastic Schwann cells, and typically presenting with hearing loss. The traditional belief that hearing deficit is caused by physical expansion of the VS, compressing the auditory nerve, does not explain the common clinical finding that patients with small tumors can have profound hearing loss, suggesting that tumor-secreted factors could influence hearing ability in VS patients. We conducted profiling of patients' plasma for 66 immune-related factors in patients with sporadic VS (N>170) and identified and validated candidate biomarkers associated with tumor size (S100B) and hearing (MCP-3). We further identified a 9-biomarker panel (TNR-R2, MIF, CD30, MCP-3, IL-2R, BLC, TWEAK, eotaxin, S100B) with outstanding discriminatory ability for VS. These findings revealed possible therapeutic targets for VS, providing a unique diagnostic tool that may predict hearing change and tumor growth in VS patients, and may inform the timing of tumor resection to preserve hearing.

Corticosterone and immune responses to dehydration in squamate reptiles

Many environments present some degree of seasonal water limitations; organisms that live in such environments must be adapted to survive periods without permanent water access. Often this involves the ability to tolerate dehydration, which can have adverse physiological effects and is typically considered a physiological stressor. While having many functions, the hormone corticosterone (CORT) is often released in response to stressors, yet increasing plasma CORT while dehydrated could be considered maladaptive, especially for species that experience predictable bouts of dehydration and have related coping mechanisms. Elevating CORT could reduce immunocompetence and have other negative physiological effects. Thus, such species likely have CORT and immune responses adapted to experiencing seasonal droughts. We evaluated how dehydration affects CORT and immune function in eight squamate species that naturally experience varied water limitation. We tested whether hydric state affected plasma CORT concentrations and aspects of immunocompetence (lysis, agglutination, bacterial killing ability, and white blood cell counts) differently among species based on how seasonally water limited they are and whether this is constrained by phylogeny. The species represented four familial pairs, with one species of each pair inhabiting environments with frequent access to water and one naturally experiencing extended periods (>30 days) with no access to standing water. The effects of dehydration on CORT and immunity varied among species. Increases in CORT were generally not associated with reduced immunocompetence, indicating CORT and immunity might be decoupled in some species. Interspecies variations in responses to dehydration were more clearly grouped by phylogeny than habitat type.

Data from: Mouse gingival single cell transcriptomic atlas identified a novel fibroblast subpopulation activated to guide oral barrier immunity in periodontitis

Periodontitis, one of the most common non-communicable diseases, is characterized by chronic oral inflammation and uncontrolled tooth supporting alveolar bone resorption. Its underlying mechanism to initiate aberrant oral barrier immunity has yet to be delineated. Here, we report a unique fibroblast subpopulation activated to guide oral inflammation (AG fibroblasts) identified in a single-cell RNA sequencing gingival cell atlas constructed from the mouse periodontitis models. AG fibroblasts localized beneath the gingival epithelium and in the cervical periodontal ligament responded to the ligature placement and to the discrete topical application of Toll-like receptor stimulants to mouse maxillary tissue. The upregulated chemokines and ligands of AG fibroblasts linked to the putative receptors of neutrophils in the early stages of periodontitis. In the established chronic inflammation, neutrophils together with AG fibroblasts appeared to induce type 3 innate lymphoid cells (ILC3s) that were the primary source of interleukin-17 cytokines. The comparative analysis of Rag2-/- and Rag2gc-/- mice suggested that ILC3 contributed to the cervical alveolar bone resorption interfacing the gingival inflammation. We propose that the AG fibroblast–neutrophil–ILC3 axis as a previously unrecognized mechanism which could be involved in the complex interplay between oral barrier immune cells contributing to pathological inflammation in periodontitis.

opencc-by-4.0Nov 2023View details →

Genetic variants regulating the immune response improve the prediction of COVID-19 severity provided by clinical variables

Data set generated to evaluate the association between SNPs from genes related to SARS-CoV-2 pathogenesis and their clinical outcome.

Data from: Larval diet and temperature alter mosquito immunity and development: using body size and developmental traits to track carry-over effects on longevity

Background: Estimating arbovirus transmission potential requires a mechanistic understanding of how environmental factors influence the expression of adult mosquito traits. While preimaginal exposure to environmental factors can have profound effects on adult traits, tracking and predicting these effects remains challenging. Methods: Using Aedes albopictus and a structural equation modelling approach, we explored how larval nutrition and temperature jointly affect development rate and success, body size, and whether these metrics capture carry-over effects on adult longevity. Additionally, we investigated how larval diet and temperature affect the baseline expression of ten immune genes. Results: We found that larval development success was primarily determined by diet, while temperature and diet both affected development rate, pupal wet weight, and wing length. Effects of diet on both morphometric measures and their relationships to adult longevity were asymmetrical, with wing length having a positive association and pupal weight a negative association. Larval diet indirectly affected adult longevity, and the time to pupation was negatively correlated with longevity. The expression of eight immune genes from Toll, JAK-STAT, and Imd pathways was enhanced in mosquitoes with higher nutrition. Conclusions: Our results highlight deficiencies from using a single body size measure to capture carry-over effects on adult traits. Further studies of larval development rate under varying environmental conditions and its potential for tracking carry-over effects on vectorial capacity are warranted.

opengpl-3.0-or-laterNov 2023View details →

Multiomics analyses reveal a Type III-associated immune response in immunotherapy-induced toxicity in melanoma and identifies potential new therapeutic targets

Immune checkpoint inhibitors (ICIs) are standard-of-care for the treatment of advanced melanoma, but their use is limited by immune-related adverse events (irAEs). Proteomic analyses and multiplex cytokine/chemokine assays from serum at baseline and at irAEs onset in melanoma patients indicated aberrant T-cell activity with differential expression of Type I and III immune signatures. This was in line with an increase in the proportions of monocytes and decrease of IL-17A-producing CD4+ T-cells in the peripheral blood using single cell RNA sequencing. Multiplex immunohistochemistry and spatial transcriptomics on ICI-induced skin rash and colitis showed an increase in the proportion of CD4+ T-cells with IL-17A expression.   Anti-IL-17A mAbs were administered in two patients with myocarditis, colitis and skin rash with resolution of the irAE. This study highlights the potential role of Type III CD4+ T-cells in irAEs development and provides proof-of-principle evidence for a corresponding clinical trial using anti-IL17A for treating irAEs. Code to generate the figures are located at https://github.com/pcheng84/AE_analysis/