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opencc-zeroAug 2021View details →

Transcriptomics Reveal Specific Molecular Mechanisms Underlying Transgenerational Immunity in Manduca sexta

The traditional view of innate immunity in insects is that every exposure to a pathogen triggers an identical and appropriate immune response, and that prior exposures to pathogens do not confer any protective (i.e. adaptive) effect against subsequent exposure to the same pathogen. This view has been challenged by experiments demonstrating that encounters with sub-lethal doses of a pathogen can prime the insect's immune system and thus, have protective effects against future lethal doses. Immune priming has been reported across several insect species, including the red flour beetle, the honeycomb moth, the bumblebee, and the European honeybee, among others. Immune priming can also be trans-generational where the parent's pathogenic history influences the immune response of its offspring. Phenotypic evidence of transgenerational immune priming (TGIP) exists in the tobacco moth Manduca sexta where first instar progeny of mothers injected with the bacterium Serratia marcescens exhibited a significant increase of in-vivo bacterial clearance. To identify the gene expression changes underlying TGIP in Manduca sexta, we performed transcriptome-wide, trans-generational differential gene expression analysis on mothers and their offspring after mothers were exposed to S. marcescens. We are the first to perform transcriptome-wide analysis of the gene expression changes associated with TGIP in this ecologically relevant model organism. We show that maternal exposure to both heat-killed and live S. marcescens has strong and significant trans-generational impacts on gene expression patterns in their offspring, including up-regulation of peptidoglycan recognition protein, toll-like receptor 9, and the antimicrobial peptide cecropin.

opencc-zeroSep 2021View details →

A peripheral immune signature of labor induction

Approximately 1 in 4 pregnant women in the United States undergo labor induction. The onset and establishment of labor, particularly induced labor, is a complex and dynamic process influenced by multiple endocrine, inflammatory, and mechanical factors as well as obstetric and pharmacological interventions. The duration from labor induction to the onset of active labor remains unpredictable. Moreover, prolonged labor is associated with severe complications for the mother and her offspring, most importantly chorioamnionitis, uterine atony, and postpartum hemorrhage. While maternal immune system adaptations that are critical for the maintenance of a healthy pregnancy have been previously characterized, the role of the immune system during the establishment of labor is poorly understood. Understanding maternal immune adaptations during labor initiation can have important ramifications for predicting successful labor induction and labor complications in both induced and spontaneous types of labor. The aim of this study was to characterize labor-associated maternal immune system dynamics from labor induction to the start of active labor. Serial blood samples from fifteen participants were collected immediately prior to labor induction (baseline) and during the latent phase until the start of active labor. Using high-dimensional mass cytometry, a total of 1,059 single-cell immune features were extracted from each sample. A multivariate machine-learning method was employed to characterize the dynamic changes of the maternal immune system after labor induction until the establishment of active labor. A cross-validated linear sparse regression model (least absolute shrinkage and selection operator, LASSO) predicted the minutes since induction of labor with high accuracy (R = 0.86, p = 6.7e-15, RMSE = 277 min). Immune features most informative for the model included STAT5 signaling in central memory CD8+ T cells and pro-inflammatory STAT3 signaling responses across multiple adaptive and innate immune cell subsets. Our study reports a peripheral immune signature of labor induction, and provides important insights into biological mechanisms that may ultimately predict labor induction success as well as complications, thereby facilitating clinical decision-making to improve maternal and fetal well-being.

opencc-zeroSep 2021View details →

Large‐scale genome sampling reveals unique immunity and metabolic adaptations in bats

Comprising more than 1,400 species, bats possess adaptations unique among mammals including powered flight, unexpected longevity given small body size, and extraordinary immunity. Some of the molecular mechanisms underlying these unique adaptations includes DNA repair, metabolism and immunity. However, analyses have been limited to a few divergent lineages, reducing the scope of inferences on gene family evolution across the Order Chiroptera. We conducted an exhaustive comparative genomic study of 37 bat species encompassing a large number of lineages, with a particular emphasis on multi-gene family evolution across immune system and metabolic genes. Genomes were obtained from public repositories and one genome (Phyllostomus hastatus) was assembled de novo. In agreement with previous analyses, we found lineage-specific expansions of the APOBEC3 and MHC-I gene families, and loss of the proinflammatory PYHIN gene family. We inferred more than 1,000 gene losses unique to bats, including genes involved in the regulation of inflammasome pathways such as epithelial defense receptors, the natural killer gene complex and the interferon-gamma induced pathway. Gene set enrichment analyses revealed genes lost in bats are involved in defense response against pathogen-associated molecular patterns and damage-associated molecular patterns. Gene family evolution and selection analyses indicate bats have evolved fundamental functional differences compared to other mammals in both innate and adaptive immune system, with the potential to enhance anti-viral immune response while dampening inflammatory signaling. In addition, metabolic genes have experienced repeated expansions related to convergent shifts to plant-based diets. Our analyses support the hypothesis that, in tandem with flight, ancestral bats had evolved a unique set of immune adaptations whose functional implications remain to be explored.

opencc-zeroSep 2021View details →

Changes in body surface temperature play an under-appreciated role in the avian immune response

Fever and hypothermia are well characterized components of systemic inflammation. However, our knowledge of the mechanisms underlying such changes in body temperature is largely limited to rodent models and other mammalian species. In mammals, high dosages of an inflammatory agent (e.g., lipopolysaccharide, LPS) typically leads to hypothermia (decrease in body temperature below normothermic levels), which is largely driven by a reduction in thermogenesis, and not changes in peripheral vasomotion (i.e., changes in blood vessel tone). In birds, however, hypothermia occurs frequently, even at lower dosages, but the thermoeffector mechanisms associated with the response remain unknown. We immune-challenged zebra finches (Taeniopygia guttata) with LPS and monitored changes in subcutaneous temperature and energy balance (i.e., body mass, food intake), and assessed surface temperatures of, and heat loss across, the eye region, bill, and legs. We hypothesized that if birds employ similar thermoregulatory mechanisms to similarly-sized mammals, LPS-injected individuals would reduce subcutaneous body temperature and maintain constant surface temperatures when compared with saline-injected individuals. Instead, LPS-injected individuals showed a slight elevation in body temperature, and this response coincided with a reduction in peripheral heat loss, particularly across the legs, as opposed to changes in energy balance. However, we note that our interpretations should be taken with caution due to small sample sizes within each treatment. We suggest that peripheral vasomotion, allowing for heat retention, is an underappreciated component of the sickness-induced thermoregulatory response of small birds.

opencc-by-4.0Dec 2018View details →

Code and Data to recreate figures from: Activation of immune receptor Rx1 triggers distinct immune-responses culminating in cell death after four hours.

Code and Data to recreate figures from: Activation of immune receptor Rx1 triggers distinct immune-responses culminating in cell death after four hours. <a href="https://doi.org/10.1111/mpp.12776">https://doi.org/10.1111/mpp.12776</a>   These files are also on Github: https://github.com/MolPlantPathology/PMID-30537296-

opencc-zeroOct 2022View details →

m6A modifications regulate intestinal immunity and rotavirus infection

N6-methyladenosine (m6A) is an abundant mRNA modification and affects many biological processes. However, how m6A levels are regulated during physiological or pathological processes such as virus infections, and the in vivo function of m6A in the intestinal immune defense against virus infections are largely unknown. Here, we uncover a novel antiviral function of m6A modification during rotavirus (RV) infection in small bowel intestinal epithelial cells (IECs). We found that rotavirus infection induced global m6A modifications on mRNA transcripts by down-regulating the m6a eraser ALKBH5. Mice lacking the m6A writer enzymes METTL3 in IECs (Mettl3ΔIEC) were resistant to RV infection and showed increased expression of interferons (IFNs) and IFN-stimulated genes (ISGs). Using RNA-sequencing and m6A RNA immuno-precipitation (RIP)-sequencing, we identified IRF7, a master regulator of IFN responses, as one of the primary m6A targets during virus infection. In the absence of METTL3, IECs showed increased Irf7 mRNA stability and enhanced type I and III IFN expression. Deficiency in IRF7 attenuated the elevated expression of IFNs and ISGs and restored susceptibility to RV infection in Mettl3ΔIEC mice. Moreover, the global m6A modification on mRNA transcripts declined with age in mice, with a significant drop from 2 weeks to 3 weeks post birth, which likely has broad implications for the development of intestinal immune system against enteric viruses early in life. Collectively, we demonstrated a novel host m6A-IRF7-IFN antiviral signaling cascade that restricts rotavirus infection in vivo.

opencc-by-4.0Nov 2022View details →

Dataset related to article "Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases"

This record contains data related to article “Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases” The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p &lt; 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of &gt;1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80-98, p &lt; 0.0001). Moreover, in the seroconverted patients, a daily dose of &gt;1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of &gt;1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease. .

opencc-zeroJan 2023View details →

FasL microgels induce immune acceptance of islet allografts in nonhuman primates

Islet transplantation to treat insulin-dependent diabetes is greatly limited by the need for maintenance immunosuppression. We report a strategy through which cotransplantation of allogeneic islets and streptavidin (SA)–FasL–presenting microgels to the omentum under transient rapamycin monotherapy resulted in robust glycemic control, sustained C-peptide levels, and graft survival in diabetic nonhuman primates for >6 months. Surgical extraction of the graft resulted in prompt hyperglycemia. In contrast, animals receiving microgels without SA-FasL under the same rapamycin regimen rejected islet grafts acutely. Graft survival was associated with increased number of FoxP3 + cells in the graft site with no significant changes in T cell systemic frequencies or responses to donor and third-party antigens, indicating localized tolerance. Recipients of SA-FasL microgels exhibited normal liver and kidney metabolic function, demonstrating safety. This localized immunomodulatory strategy succeeded with unmodified islets and does not require long-term immunosuppression, showing translational potential in β cell replacement for treating type 1 diabetes.

opencc-by-4.0Jul 2021View details →

Supplementary Data for: Intraspecific diversity in the wild tomato species Solanum chilense in initial immune responses towards a glucan elicitor

This repository contains: Read count data for the RNASeq as reported in the paper ) All scripts used for the RNASeq analysis   ) a table describing DEGs with known homologous gene   ) a table describing DEGs with known homologous genes ) All data underlying the graphs related to the quantification of defence responses and plotting the result, sorted by figure.

Single-cell heterogeneity of EGFR and CKD4 co-amplification is linked to immune infiltration in glioblastoma

This upload contains RDS objects of preprocessed publicly available scRNAseq data, required to run scRNAseq analyses in the manuscript "Single cell heterogeneity of EGFR and CDK4 co-amplification is linked to immune infiltration in glioblastoma". The corresponding GitHub repo <a href="https://github.com/Michorlab/GBM_OR_immune">https://github.com/Michorlab/GBM_OR_immune</a> contains code to analyze the data here, as well as plots and tables generated on the basis of this data.

Data and code for "The immune regulation and epidemiological consequences of specific immune priming in Drosophila"

Raw data and R code used to analyse and generate all figures in the above manuscript.

opencc-by-4.0Oct 2022View details →

Immune Thrombocytopenia: Background rates literature review and visualization

Immune Thrombocytopenia: Background rates literature review and forest plots for visualization

Genetic variation in cis-regulatory domains suggests cell type-specific regulatory mechanisms in immunity

1- workflow for data analysis and figures generation

Data for manuscript Trans-generational immune priming against American Foulbrood does not affect the performance of honeybee colonies

Data used in analysis for manuscript Trans-generational immune priming against American Foulbrood does not affect the performance of honeybee colonies

opencc-by-4.0Mar 2023View details →

Pleiotropy promotes the evolution of inducible immune responses in a model of host-pathogen coevolution

The archives uploaded here include the code used to perform the evolutionary simulations as described in Pleiotropy promotes the evolution of inducible immune responses in a model of host-pathogen coevolution authors: Martin,R. Tate, A. as well as the data that was used in the generation of the figures for that paper. Code requires the Julia programming language and necessary packages to run.

opencc-zeroFeb 2023View details →

Data from: Use of an exotic host plant shifts immunity, chemical defense, and viral burden in wild populations of a specialist insect herbivore

Defense against natural enemies constitutes an important driver of herbivore host range evolution in the wild. Populations of the Baltimore checkerspot butterfly, Euphydryas phaeton (Nymphalidae), have recently incorporated an exotic plant, Plantago lanceolata (Plantaginaceae), into their dietary range. To understand the tritrophic consequences of utilizing this exotic host plant, we examined immune performance, chemical defense, and interactions with a natural entomopathogen (Junonia coenia densovirus, Parvoviridae) across wild populations of this specialist herbivore. We measured three immune parameters, sequestration of defensive iridoid glycosides (IGs), and viral infection load in field-collected caterpillars using either P. lanceolata or a native plant, Chelone glabra (Plantaginaceae). We found that larvae using the exotic plant exhibited reduced immunocompetence, compositional differences in IG sequestration, and higher in situ viral burdens compared to those using the native plant. On both host plants, high IG sequestration was associated with reduced hemocyte concentration in the larval hemolymph, providing the first evidence of incompatibility between sequestered chemical defenses and the immune response (i.e., the "vulnerable host" hypothesis) from a field-based study. However, despite this negative relationship between IG sequestration and cellular immunity, caterpillars with greater sequestration harbored lower viral loads. While survival of virus-infected individuals decreased with increasing viral burden, it ultimately did not differ between the exotic and native plants. These results provide evidence that (1) phytochemical sequestration may contribute to defense against pathogens even when immunity is compromised, and (2) herbivore persistence on exotic plant species may be facilitated by sequestration and its role in defense against natural enemies.

opencc-zeroMar 2023View details →

Data for: Immune genotypes, immune responses, and survival in a wild bird population

Individuals vary in their immune genotype, inbreeding coefficient f, immune responses, survival to adulthood, and adult longevity. However, whether immune genes predict survival or longevity, whether such relationships are mediated through immune responses, and how f affects immune genotype remain unclear. We use a wild song sparrow (Melospiza melodia) population in which survival to adulthood, adult longevity, and f were measured precisely, and in which immune responses have previously been assessed. We investigate four toll-like receptors (TLR) and the major histocompatibility complex (MHC) class IIB exon 2 genes. We test: a) whether immune genes predict fitness (survival to adulthood or adult longevity); b) whether immune genes predict immune response; c) whether immune response predicts fitness; and d) whether fitness, immune responses, or immune genotypes are correlated with f. We find that survival to adulthood is not associated with immune gene variation, but adult longevity is decreased by high MHC allele diversity (especially in birds that were relatively outbred), and by the presence of a specific MHC supertype. Immune responses were affected by specific immune genotypes. Survival to adulthood and adult longevity were not predicted by immune response, implying caution in the use of immune response as a predictor for fitness. We also found no relationship between f and immune genotype. This finding indicates that immune gene associations with longevity and immune response are not artefacts of f, and suggests that pathogen-mediated selection at functional loci can slow the loss of genetic variation arising from genetic drift and small population size.

opencc-by-4.0Mar 2023View details →

Immune Checkpoint Inhibitor, Nivolumab, Combined with Chemotherapy Improved the Survival of Unresectable Ad-vanced and Metastatic Esophageal Squamous Cell Carcinoma: a real world experience

Figure S1 the detail of treatments. Blue arrow means this patient was still alive at the latest date of follow up. Hollow circle means this patient die. The others were lose follow up at the latest date of follow up. Figure S2 progression free survival (PFS) of patients received immunotherapy, including 5 nivolumab and chemotherapy and 1 dual immune check point inhibitor, on different PD-L1 tumor cells (TC) expression. (A) divided by PD-L1 TC <1% or ≧1%. (B)divided by PD-L1 TC <10% or ≧10%.

opencc-zeroMar 2023View details →

Data for: Low protease activity in B cell follicles promotes retention of intact antigens after immunization

The structural integrity of vaccine antigens is critical to the generation of protective antibody responses, but the impact of protease activity on vaccination in vivo is poorly understood. We characterized protease activity in lymph nodes and found that antigens were rapidly degraded in the subcapsular sinus, paracortex, and interfollicular regions, whereas low protease activity and antigen degradation rates were detected in the vicinity of follicular dendritic cells (FDCs). Correlated with these findings, immunization regimens designed to target antigen to FDCs led to germinal centers dominantly targeting intact antigen, whereas traditional immunizations led to much weaker responses that equally targeted the intact immunogen and antigen breakdown products. Thus, spatially compartmentalized antigen proteolysis affects humoral immunity and can be exploited.