Immune System Genes Research Articles

APOBEC3G Is a p53-Dependent Restriction Factor in Respiratory Syncytial Virus Infection of Human Cells Included in the p53/Immune Axis.

Identifying and understanding genetic factors that influence the propagation of the human respiratory syncytial virus (RSV) can lead to health benefits and possibly augment recent vaccine approaches. We previously identified a p53/immune axis in which the tumor suppressor p53 directly regulates the expression of immune system genes, including the seven members of the APOBEC3 family of DNA cytidine deaminases (A3), which are innate immune sentinels against viral infections. Here, we examined the potential p53 and A3 influence in RSV infection, as well as the overall p53-dependent cellular and p53/immune axis responses to infection. Using a paired p53 model system of p53+ and p53- human lung tumor cells, we found that RSV infection activates p53, leading to the altered p53-dependent expression of A3D, A3F, and A3G, along with p53 site-specific binding. Focusing on A3G because of its 10-fold-greater p53 responsiveness to RSV, the overexpression of A3G can reduce RSV viral replication and syncytial formation. We also observed that RSV-infected cells undergo p53-dependent apoptosis. The study was expanded to globally address at the transcriptional level the p53/immune axis response to RSV. Nearly 100 genes can be directly targeted by the p53/immune axis during RSV infection based on our p53BAER analysis (Binding And Expression Resource). Overall, we identify A3G as a potential p53-responsive restriction factor in RSV infection. These findings have significant implications for RSV clinical and therapeutic studies and other p53-influenced viral infections, including using p53 adjuvants to boost the response of A3 genes.

Effects of Dietary Sodium Propionate on Growth, Digestive Enzyme Activity, and Expression of Immune System Genes in Juveniles of Tropical Gar (Atractosteus tropicus)

We determined the effects of sodium propionate (SP) added to the diets of Atractosteus tropicus juveniles with respect to the growth, survival, digestive enzyme activity, and expression of genes that are associated with the immune system. Five treatments (0, 0.5, 1.0, 1.5, and 2.0%) were evaluated in triplicate on 180 fish (3.65 ± 0.12 g) distributed among 15 (70 L) tanks. The juveniles were fed five times a day with 5% feed in relation to the biomass of the organism. The treatment with 0.5% SP showed a final weight value of 25.7 ± 4.5 g, absolute weight of gain (AWG) of 21.93 ± 4.39 g, and specific growth rate (SGR) of 3.1 ± 0.26. Treatments with 1.5 and 2.0% SP showed the highest survival (91.6%). The control group (0%) showed a greater activity of lipases. There was a tendency that the highest activity of alkaline proteases and chymotrypsin occurred in the 0 and 0.5% treatments. The maximum relative expression of the genes ocln, muc2, and nod2 occurred in the 1.5% treatment. The inclusion of SP in the diet of A. tropicus juveniles could benefit the activity of some digestive enzymes as well as the expression of genes related to the function of the intestinal barrier, therefore benefitting the survival of the organisms.

New insights into ancestry and health of Polynesians and New Zealand Māori

We are now moving towards the new era of personalised medicine. In prospect, a DNA-tailored healthcare system will utilise genomic information from patients and populations for the prevention and treatment of diseases. This near-future medicine recognises that there is already evidence of genetic disparity between people of different ethnicity. Our own previous genetic surveys of human genomes have demonstrated abundant genetic variation in New Zealanders. These now include extensive new work on immune system genes. We have produced a comprehensive reference set of genotypes for clinically relevant antigens in transplantation (human leukocyte antigen, major histocompatibility complex class I chain-related gene A and killer cell immunoglobulin-like receptor) and transfusion (blood group and human platelet antigens) medicine in Māori and Polynesians. This report sets these data in context and highlights allelic variations and their implications for ancestry and health. It is hoped that this information may help to resolve some of the present inequalities in Māori and Pacific health status.

Gene-Centric Association Scans of Pleiotropic Immune-Mediated Disease Genes in the PATH Study Identify Novel Determinants of Factor VIII Inhibitor Risk in Hemophilia-A Patients and Confirm Race as an Independent Predictor

Hemophilia-A (HA) is caused by heterogeneous loss-of-function factor (F) VIII gene ( F8) mutations and deficiencies in plasma FVIII coagulant activity (FVIII:C) that impair intrinsic pathway coagulation amplification. The standard-of-care for severe HA patients is regular infusions of therapeutic FVIII proteins (tFVIIIs) but ~25-30% of all such subjects develop neutralizing anti-tFVIII-antibodies called “FVIII inhibitors (FEIs)” that leave them refractory to treatment and necessitate use of alternative therapies that are less safe and effective, and extremely expensive. We used the ImmunoChip genotyping platform and subjects in the Personalized Alternative Therapies for Hemophilia (PATH) study to scan immune-mediated disease (IMD) genes for novel and/or replicated genomic sequence variations associated with FEI risk while accounting for non-independence of data due to genetic relatedness and F8 mutational heterogeneity. The “enrollment-FEI-status” of 450 North American PATH study subjects-which include 446 that self-identified as being only either black-African (n=204) or white-European (n=242), and four that self-identified as being both white-European and either black-African (n=3) or Asian (n=1)-was the dependent variable. The F8 mutation data and a genetic relatedness matrix were incorporated into a binary linear mixed model of genetic association with the novel FEI outcome of enrollment-FEI-status based on whether or not FEIs of any titer (AT) developed-Yes (AT:FEIs+) versus No (AT:FEI-)-regardless of their “historical-FEI-status', i.e., whether or not they had ever developed FEIs of AT prior to study entry. We adopted a gene-centric association strategy to scan as ”candidates“ a subset of 101 genes-of the ~2,000 total immune system genes that are interrogated by the naturally occurring sequence variations able to be genotyped simultaneously on the ImmunoChip-which comprise what we refer to herein as ”pleiotropic-IMD-genes“ because they have been implicated previously in the development of either (i) two or more autoimmune diseases (n=80) or (ii) at least one autoimmune disease if they were also implicated in FEI risk previously (n=25). (Note that four of the pleiotropic-IMD-genes previously implicated in FEI risk were also in the 80 genes implicated previously in the development of multiple autoimmune diseases such that we scanned 101 distinct pleiotropic-IMD-genes for association with FEI development in the PATH study.) Enrollment-FEI-status was significantly associated with SNPs in NOS2A ( Figure 1) and B3GNT2 ( Figure 2), which are involved directly and indirectly, respectively, in anti-microbial-/-tumoral-immunity. Among the pleiotropic-IMD-genes previously implicated in FEI risk, we identified strong associations with SNPs in CTLA4 (p=2.2E-5). We also quantified the influence of the different F8 mutation types on FEI risk for the first time and demonstrated that the F8-mutation-effect underlies ~15% of the total heritability of FEI development. The additive genetic heritability together with the SNPs in the pleiotropic-IMD-genes were found to account for >50% of the patient-specific variability in FEI risk. Finally, race was shown to be a significant determinant of FEI risk independent of the effects of F8 mutation types and non- F8-genetics.

Pathogenicity of microsclerotia from Metarhizium robertsii against Aedes aegypti larvae and antimicrobial peptides expression by mosquitoes during fungal-host interaction

Aedes aegypti is a vector of various disease-causing arboviruses. Chemical insecticide-based methods for mosquito control have increased resistance in different parts of the world. Thus, alternative control agents such as the entomopathogenic fungi are excellent candidates to control mosquitoes as part of an ecofriendly strategy. There is evidence of the potential of entomopathogenic fungal conidia and blastospores for biological control of eggs, larval and adult stages, as well as the pathogenicity of fungal microsclerotia against adults and eggs. However, there are no studies on the pathogenicity of microsclerotia against either aquatic insects or insects that develop part of their life cycle in the water, such as the A. aegypti larvae. In this study, we assayed the production of microsclerotia and their pathogenicity against A. aegypti larvae of two isolates of Metarhizium robertsii, i.e., CEP 423 isolated in La Plata, Argentina, and the model ARSEF 2575. Both isolates significantly reduced the survival of A. aegypti exposed to their microsclerotia. The fungus-larva interaction resulted in a delayed response in the host. This was evidenced by the expression of some humoral immune system genes such as defensins and cecropin on the 9th day post-infection, when the fungal infection was consolidated as a successful process that culminates in larvae mortality. In conclusion, M. robertsii microsclerotia are promising propagules to be applied as biological control agents against mosquitoes since they produce pathogenic conidia against A. aegypti larvae.

Severe combined immunodeficiency with a homozygous c.464T>C (p.Leu155Pro) mutation in the RAG2 gene in a country without neonatal screening: Report of two clinical cases

Introduction: Severe combined immunodeficiency (SCID) is a disorder belonging to the broad spectrum of inborn errors of immunity (IEI), characterized by a predisposition to develop recurrent, severe, difficult-to-treat opportunistic infections. This disorder is associated with abnormalities in genes of the adaptive immune system and should be suspected in patients with infections during the first months of life, mainly due to fungal pathogens and intracellular agents. Case Presentation: Two cases of SCID diagnosed at the General Hospital with Specialties "Juan María de Salvatierra” in Baja California Sur (BCS), México in 2022 are described. The first patient presented persistent candidiasis stomatitis with no response to oral treatment. The second patient presented mycotic dermatitis and oropharyngeal candidiasis compatible with Candida albicans and multiple episodes of multi-treated airway infection with partial remission. The diagnosis was completed with a genetic panel that showed a mutation in RAG2 homozygous variant c.464T>C (p.Leu155Pro) in both patients. Conclusions: SCID should be considered in patients with recurrent and difficult-to-treat infectious diseases in the first months of life. For its timely detection, implementing neonatal screening quantifying of T-cell receptor excision circles (TRECs) is recommended. This method is not available in Mexico, so it has been relevant to have physicians trained in the timely clinical identification of the disease. Thanks to the prompt referral of both patients to our hospital, we could treat the comorbidities associated with SCID, provide a specific molecular diagnosis, and transfer the patients to a hospital specialized in bone marrow transplantation for definitive treatment.

In ovo feeding of probiotic lactobacilli differentially alters expression of genes involved in the development and immunological maturation of bursa of Fabricius in pre-hatched chicks

Compelling evidence indicates that immunological maturation of the gut-associated lymphoid tissues, including the bursa of Fabricius, is dependent upon antigenic stimulation post-hatch. In view of these data, the present study investigated the impact of exposing the immune system of chick embryos to antigenic stimuli, via in ovo delivery of poultry-specific lactobacilli, on the expression of genes associated with early bursal development and maturation. Broiler line embryonated eggs were inoculated with 106 and 107 colony-forming units (CFUs) of an individual or a mixture of Lactobacillus species, including L. crispatus (C25), L. animalis (P38), L. acidophilus (P42), and L. reuteri (P43), at embryonic day 18 (ED18). The bursa of Fabricius was collected from pre-hatched chicks (ED20) to measure the expression levels of various immune system genes. The results revealed that L. acidophilus and the mixture of Lactobacillus species at the dose of 106 CFU consistently elicited higher expression of genes responsible for B cell development, differentiation, and survival (B cell activating factor (BAFF), BAFF-receptor (BAFF-R)), and antibody production (interleukin (IL)-10) and diversification (TGF-β). Similar expression patterns were also noted in T helper (Th) cell-associated cytokine genes, including Th1-type cytokines (interferon (IFN)-γ and IL-12p40), Th2-type cytokines (IL-4 and IL-13) and Th17 cytokine (IL-17). Overall, these results suggest that the supplementation of poultry-specific lactobacilli to chick embryos might be beneficial for accelerating the development and immunological maturation of the bursa of Fabricius. However, further studies are required to determine if the changes in gene expression are associated with the developmental trajectory and phenotypes of bursal cells.

Effects of black soldier fly meal feeding on rainbow trout gut microbiota, immune-related gene expression, and Lactococcus petauri resistance

Abstract Providing a sustainable and affordable food supply is one of the most significant challenges facing the global aquaculture industry. Black soldier fly (BSF), Hermetia illucens, meal is a particularly promising alternative to animal-derived protein sources. Following a 90-day feeding experiment with four different diets containing BSF meal with increasing fish meal replacement levels of 25%, 50%, 75%, and 100%, designated as B25, B50, B75, and B100, and a control diet (B0) without BSF meal, the gut microbiota, immune-related gene expression, and Lactococcus petauri resistance of rainbow trout (Oncorhynchus mykiss) were studied. Regardless of diet, rainbow trout intestinal microbiota were different from those in water. In the intestinal mucosa, Fusobacteria, Firmicutes, and Proteobacteria were among the most prevalent taxa. Rainbow trout fed with a BSF-containing diet had a higher bacterial diversity in their gastrointestinal tract than fish fed with a control diet. The abundance of Firmicutes, Actinobacteria, and Proteobacteria increased in tandem with the replacement rate of fish meal with BSF meal. The B75-fed fish were found to be the most resistant group to L. petauri, followed by the groups fed with B100, B50, and B25. Compared to the control group, the expression of cytokines (Tgf, Il-10, Il-1β, , and Il-8) and immune-related genes (IgM, IgT, Mhc-II, and Tlr-5) increased significantly () in all fish groups fed with a BSF-containing diet. Substituting fish meal with BSF meal beyond 50% enhanced the survival rates of fish infected with L. petauri. Furthermore, BSF-containing diets boosted the immune system and cytokine-related genes in fish. Due to improved survival and immunity, rainbow trout may be fed a 50% BSF meal substituted diet without removing chitin or pre-treating BSF meal.

Stress-associated β -glucan administration stimulates the TLR – MYD88 – NFKB1 signaling pathway in Nile tilapia (Oreochromis niloticus)

There is evidence that the administration of β-glucan can effectively activate several defense mechanisms, such as the Tlr-Myd88-Nfkb1 pathway that induces the expression of immune cytokines. Thus, the objective of this work was to evaluate whether β-glucan acts on the mechanisms of gene transcription via the Tlr-Myd88-Nfkb1 pathway in Nile tilapia under stress after challenge with Streptococcus agalactiae. Therefore, we evaluated the expression of immune system genes such as toll-like receptors 1 (tlr1), toll-like receptors 2 (tlr2), primary myeloid differentiation response gene (myd88) and nuclear factor kappa B1 (nfkb1). A total of 408 fish were distributed in 24 polyethylene boxes and randomly divided into eight groups with 3 replications each: C15: Tilapias received a control diet (free of β-glucan) for 15 days and were sampled after the 15th day of the experiment; C15D: Tilapias received a control diet (free of β-glucan) for 15 days, were challenged on the 14th day and were sampled at the 15th day of the experiment; β15: Tilapias received experimental diet (1g kg−1 of β-glucan) for 15 days and were sampled after 15 days; β15D: Tilapias received an experimental diet (1g kg−1 of β-glucan) for 15 days, were challenged on the 14th day and were sampled at the 15th day of the experiment; C30: Tilapias received a control diet (free of β-glucan) for 30 days and were sampled on the 30th day of the experiment; C30D: Tilapias received a control diet (free of β-glucan) for 30 days, were challenged on the 29th day and were sampled at the 30th day of the experiment; β30: Tilapias received experimental diet (1g kg-1 of β-glucan) for 30 days and were sampled after 30 days and β30D: Tilapias received experimental diet (1g kg−1 of β-glucan) for 30 days, were challenged on the 29th day and were sampled at 30 of the experiment. In the fish sampled at 15 and 30 days of the experiment, after being anesthetized and killed by brain section, cranial kidney and spleen were collected for gene expression analysis. The analyzes showed that the association of β-glucan and stressful management modulated the immune system, using the Tlr-Myd88-Nfkb1 signaling pathway, indicating that this compound can be used to promote early defense and protect fish against diseases.

Effects of dietary supplementation of lignocellulose-derived cello-oligosaccharides on growth performance, antioxidant capacity, immune response, and intestinal microbiota in rainbow trout (Oncorhynchus mykiss)

This study evaluated the prebiotic potential of cello-oligosaccharides (COS) produced from birch (Betula pendula), an under-utilised lignocellulosic source from the forestry industry, on growth performance, mucosal immunity, gut microbiota composition, and antioxidant capacity of juvenile rainbow trout (Oncorhynchus mykiss). In a 45-day trial, the fish were fed with diets containing 0%, 0.1%, 0.5% and 1.5% COS, while a diet containing fructo-oligosaccharides (0.5% FOS) was used as a positive control. Fish fed with the 0.5% and 1.5% COS diets showed significantly (P < 0.05) higher abundance of Ruminococcaceae, Bacillaceae and Lactobacillaceae, in the faecal microbiota. The COS diets also induced higher antioxidant capacity in the gut and serum, but there were no treatment effects (P > 0.05) on growth of rainbow trout. Gene expression analysis of the intestine showed significant elevation (P < 0.05) in expression of complement (c3 and c-type lectin) and receptor (tlr2) genes of the innate immune system in COS-fed fish. However, for cytokine and adaptive immune genes, no significant differences (P > 0.05) in gene transcripts were observed between the COS/FOS diets with the control diet. These results suggest that dietary cello-oligosaccharides can be a useful feed supplement for rainbow trout, which can modulate intestinal microbial communities, innate immune response and antioxidant capacity of the host.

Candidate Genetic and Molecular Drivers of Dysregulated Adaptive Immune Responses After Traumatic Brain Injury.

Abstract Neuroinflammation is a significant and modifiable cause of secondary injury after traumatic brain injury (TBI), driven by both central and peripheral immune responses. A substantial proportion of outcome after TBI is genetically mediated, with an estimated heritability effect of around 26%, but because of the comparatively small datasets currently available, the individual drivers of this genetic effect have not been well delineated. A hypothesis-driven approach to analyzing genome-wide association study (GWAS) datasets reduces the burden of multiplicity testing and allows variants with a high prior biological probability of effect to be identified where sample size is insufficient to withstand data-driven approaches. Adaptive immune responses show substantial genetically mediated heterogeneity and are well established as a genetic source of risk for numerous disease states; importantly, HLA class II has been specifically identified as a locus of interest in the largest TBI GWAS study to date, highlighting the importance of genetic variance in adaptive immune responses after TBI. In this review article we identify and discuss adaptive immune system genes that are known to confer strong risk effects for human disease, with the dual intentions of drawing attention to this area of immunobiology, which, despite its importance to the field, remains under-investigated in TBI and presenting high-yield testable hypotheses for application to TBI GWAS datasets.

Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis

ObjectivesTranscriptomic profiling of synovial tissue from patients with early, untreated rheumatoid arthritis (RA) was used to explore the ability of unbiased, data-driven approaches to define clinically relevant subgroups.MethodsRNASeq was performed...

NS1 and PA-X of H1N1/09 influenza virus act in a concerted manner to manipulate the innate immune response of porcine respiratory epithelial cells.

Live-attenuated influenza A viruses (LAIV) may be superior to inactivated or subunit vaccines since they can be administered via mucosal routes to induce local immunity in the respiratory tract. In addition, LAIV are expected to trigger stronger T-cell responses that may protect against a broader range of antigen-drifted viruses. However, the development of LAIV is challenging since a proper balance between immunogenicity and safety has to be reached. In this study, we took advantage of reverse genetics to generate three LAIV based on the pandemic H1N1 2009 (pH1N1/09) virus strain: ΔPA-X, which is defective in the synthesis of the accessory PA-X protein, NS1(1-126) lacking 93 amino acids at the C-terminus of the NS1 protein, and a combination of both. Characterization of these recombinant viruses using a novel porcine bronchiolar epithelial cell line (T3) revealed that the ΔPA-X mutant replicated similar to wild type (WT) virus. However, in contrast to the parental virus the ΔPA-X mutant allowed transcription of genes involved in cell cycle progression and limits apoptosis. The NS1(1-126) mutant also replicated comparable to WT virus, but triggered the release of type I and III IFN and several chemokines and cytokines. Surprisingly, only the NS1(1-126)/ΔPA-X double mutant was significantly attenuated on T3 cells, and this was associated with enhanced transcription of genes of the innate immune system and complete absence of apoptosis induction. In conclusion, these findings indicate that NS1 and PA-X act in a concerted manner to manipulate the host cell response, which may help to develop swine LAIV vaccine with a more favorable balance of safety and immunogenicity.

420 Molecular assessment of atopic dermatitis and psoriasis samples collected using a noninvasive technique

Abstract Updates in the molecular understanding of common and often debilitating skin diseases such as atopic dermatitis (AD) and psoriasis led to the development of multiple targeted systemic drugs. Optimal response to these medications relies on correct diagnosis, as well as clinical, personal and molecular factors unique to each patient. Currently, unstandardized assessment of clinical characteristics and comorbidities drive the development of a therapeutic plan for patients with AD and psoriasis. The molecular mechanisms underlying each patient’s disease are not routinely assessed when developing a treatment plan. This empirical approach to treatment selection delays optimal therapeutic response and leads to increased costs to healthcare systems. Therefore, incorporating molecular information from an individual patient’s disease should inform better treatment decisions. Previously, we presented the proof of concept for a noninvasive skin scraping sample collection technique by assessing gene expression differences of select genes of interest from psoriasis and AD samples using quantitative polymerase chain reaction. Indeed, candidate genes were differentially expressed in AD and psoriasis lesions relative to nonlesional skin and in AD relative to psoriasis lesions, demonstrating the feasibility of this collection technique. An algorithm based on the gene expression profiles of AD and psoriasis samples could be used to help guide therapy selection. This study aims to assess the molecular profiles of AD and psoriasis samples collected using a noninvasive skin scraping method with the ultimate goal of developing and validating a molecular test for these common inflammatory skin diseases. The superficial epidermis of lesional and nonlesional skin from patients with AD or psoriasis from three dermatology centers in the USA was collected by gently scraping the skin 10 times with a curette and immediately preserving the sample in a proprietary buffer. RNA isolated from samples was stored at −80°C until further use. Library preparation and next generation RNA sequencing was performed using the Ion AmpliSeq Transcriptome Human Gene Expression panel on the S5XL sequencer (ThermoFisher). Differential expression of genes was assessed using DESeq2; Metascape was used to assess enriched gene ontology of differentially expressed genes. When comparing AD lesional and nonlesional skin, 1633 transcripts were differentially expressed (absolute value of log2fold change &amp;gt;1.0 and padj &amp;lt; 0.05). Additionally, 4468 transcripts were differentially expressed between psoriasis lesional and nonlesional skin. Further, principal component analysis demonstrated that lesional and nonlesional samples for both AD and psoriasis could be distinguished by their respective gene expression profiles. Gene ontology enrichment analysis revealed that innate and adaptive immune system and cytokine signaling genes were among the most common types of differentially expressed genes between lesional and nonlesional samples. Moreover, gene expression differed between lesional AD and psoriasis samples. These results suggest that a molecular test could be developed from AD and psoriasis samples collected by a noninvasive scraping technique. Further, clinical correlation with therapeutic outcomes may be used in conjunction with molecular profiles to develop an algorithm to predict therapeutic response in these common inflammatory skin diseases.

Nanoplastics enhance the intestinal damage and genotoxicity of sulfamethoxazole to medaka juveniles (Oryzias melastigma) in coastal environment

Antibiotics and nanoplastics are widely detected in the coastal ecosystem. However, the transcriptome mechanism elucidating the effect of antibiotics and nanoplastics co-exposure on the gene expression of aquatic organisms in coastal environment is still unclear. Here, single and joint effects of sulfamethoxazole (SMX) and polystyrene nanoplastics (PS-NPs) on the intestinal health and gene expression of medaka juveniles (Oryzias melastigma), which live in coastal environment, were investigated. The SMX and PS-NPs co-exposure decreased intestinal microbiota diversity compared to the PS-NPs, and caused more adverse effect on the intestinal microbiota composition and intestinal damage compared to the SMX, indicating that PS-NPs might enhance the toxicity of SMX on the medaka intestine. The increased abundance of Proteobacteria in the intestine was observed in the co-exposure group, which might induce the intestinal epithelium damage. In addition, the differentially expressed genes (DEGs) were mainly involved in the drug metabolism-other enzymes, drug metabolism-cytochrome P450, metabolism of xenobiotics by cytochrome P450 pathways in visceral tissue after the co-exposure. The expression of the host immune system genes (e.g., ifi30) could be associated with the increased pathogens in intestinal microbiota. This study is useful for understanding the toxicity effect of antibiotics and NPs on aquatic organisms in coastal ecosystem.

Addition of β-glucans in diets for tropical gar (Atractosteus tropicus) larvae: effects on growth, digestive enzymes and gene expression of intestinal epithelial integrity and immune system.

The effect of β-glucans 1,3/1,6 from Saccharomyces cerevisiae yeast at different inclusion percentages (0.0, 0.2, 0.4, 0.6, and 0.8%) in the diet for tropical gar (Atractosteus tropicus) larvae was evaluated on growth, digestive enzyme activity and, relative expression of the immune system genes. The bioassay started on the third day after hatching (DAH) and lasted 21days, using a total of 1500 larvae of 0.055 ± 0.008g and, a total length of 2.46 ± 0.26cm. Larviculture was carried out in a recirculation system with 15 tanks of 70 L using a density of 100 organisms per experimental unit. No significant differences in larval growth were observed by the inclusion of β-glucans (p > 0.05). Digestive enzymes showed changes in lipase and trypsin activities, presenting higher values in fish fed 0.6% and 0.8% β-glucans diets compared to the other treatments (p < 0.05). Leucine-aminopeptidase, chymotrypsin, acid phosphatase, and alkaline phosphatase activity showed higher activities in larvae fed with a 0.4% β-glucan diet compared to the control group. The relative expression of intestinal membrane integrity (mucin 2) muc-2, (occludins) occ, (nucleotide-binding oligomerization domain) nod-2, and immune system lys (lysosome) genes showed over-expression in larvae fed the 0.4% β-glucan diet to the rest of the treatments (p < 0.05). The inclusion of β-glucans at 0.4-0.6% in diets for A. tropicus larvae could improve larviculture, as effects on the increase in the activity of several digestive enzymes and the expression of genes of the immune system.

Thiacloprid impairs honeybee worker learning and memory with inducing neuronal apoptosis and downregulating memory-related genes

Neonicotinoids are among the most widely used insecticides in the world and are recognized as a potential cause of pollinator decline. Previous studies have demonstrated that the neonicotinoid thiacloprid has adverse effects on foraging and memory behaviors. However, there is no direct evidence linking thiacloprid-induced neuronal cell damage in the brains of honeybees to learning and memory dysfunction. Adult honeybee (Apis mellifera L.) workers were chronically exposed to sub-lethal concentrations of thiacloprid. We discovered that thiacloprid negatively affected their survival, food consumption, and body weight. In addition, sucrose sensitivity and memory performance were impaired. We evaluated the apoptosis of honeybee brain cells using TUNEL (Terminal deoxynucleotidyl transferase-mediated digoxigenin-dUTP-biotin nick-end labeling) and Caspase-3 assays, which revealed that thiacloprid increases the dose-dependent apoptosis of neurons in the mushroom bodies (MB) and antennal lobes (AL). We also determined the abnormal transcripts of multiple genes, including vitellogenin (Vg), immune system genes (apidaecin and catalase), and memory-associated genes (pka, creb, Nmdar1, Dop2, Oa1, Oa-2R, and Oa-3R). These results indicate that exposure to sublethal concentrations of thiacloprid cause abnormal expression of memory-related genes and apoptosis of brain cells in the AL and MB, which may contribute to the memory disorder induced by thiacloprid exposure.

Exploratory Transcriptomic Profiling Reveals the Role of Gut Microbiota in Vascular Dementia.

Stroke is the second most common cause of cognitive impairment and dementia. Vascular dementia (VaD), a cognitive impairment following a stroke, is common and significantly impacts the quality of life. We recently demonstrated via gut microbe transplant studies that the gut microbe-dependent trimethylamine-N-oxide (TMAO) pathway impacts stroke severity, both infarct size and long-term cognitive outcomes. However, the molecular mechanisms that underly the role of the microbiome in VaD have not been explored in depth. To address this issue, we performed a comprehensive RNA-sequencing analysis to identify differentially expressed (DE) genes in the ischemic cerebral cortex of mouse brains at pre-stroke and post-stroke day 1 and day 3. A total of 4016, 3752 and 7861 DE genes were identified at pre-stroke and post-stroke day 1 and day 3, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated pathways of neurodegeneration in multiple diseases, chemokine signaling, calcium signaling, and IL-17 signaling as the key enriched pathways. Inflammatory response genes interleukin-1 beta (Il-1β), chemokines (C-X-C motif chemokine ligand 10 (Cxcl10), chemokine ligand 2 (Ccl2)), and immune system genes (S100 calcium binding protein 8 (S100a8), lipocalin-2 (Lcn2)) were among the most significantly upregulated genes. Hypocretin neuropeptide precursor (Hcrt), a neuropeptide, and transcription factors such as neuronal PAS domain protein 4 (Npas4), GATA binding protein 3 (Gata3), and paired box 7 (Pax7) were among the most significantly downregulated genes. In conclusion, our results indicate that higher plasma TMAO levels induce differential mRNA expression profiles in the ischemic brain tissue in our pre-clinical stroke model, and the predicted pathways provide the molecular basis for regulating the TMAO-enhanced neuroinflammatory response in the brain.

Variation in density, immune gene suppression, and coinfection outcomes among strains of the aphid endosymbiont Regiella insecticola.

Many insects harbor heritable microbes that influence host phenotypes. Symbiont strains establish at different densities within hosts. This variation is important evolutionarily because within-host density has been linked to the costs and benefits of the symbiosis for both partners. Studying the factors shaping within-host density is important to our broader understanding of host-microbe coevolution. Here we focused on different strains of Regiella insecticola, a facultative symbiont of aphids. We first showed that strains of Regiella establish in pea aphids at drastically different densities. We then found that variation in density is correlated with the expression levels of two key insect immune system genes (phenoloxidase and hemocytin), with the suppression of immune gene expression correlating with higher Regiella density. We then performed an experiment where we established coinfections of a higher- and a lower-density Regiella strain, and we showed that the higher-density strain is better able to persist in coinfections than the lower-density strain. Together, our results point to a potential mechanism that contributes to strain-level variation in symbiont density in this system, and our data suggest that symbiont fitness may be increased by establishing at higher density within hosts. Our work highlights the importance of within-host dynamics shaping symbiont evolution.

Impact of high human genetic diversity in Africa on immunogenicity and efficacy of RTS,S/AS01 vaccine.

In modern medicine, vaccination is one of the most effective public health strategies to prevent infectious diseases. Indisputably, vaccines have saved millions of lives by reducing the burden of many serious infections such as polio, tuberculosis, measles, pneumonia, and tetanus. Despite the recent recommendation by the World Health Organization (WHO) to roll out RTS,S/AS01, this malaria vaccine still faces major challenges of variability in its efficacy partly due to high genetic variation in humans and malaria parasites. Immune responses to malaria vary between individuals and populations. Human genetic variation in immune system genes is the probable cause for this heterogeneity. In this review, we will focus on human genetic factors that determine variable responses to vaccination and how variation in immune system genes affect the immunogenicity and efficacy of the RTS,S/AS01 vaccine.