Changes In Immune Function Research Articles

Global warming-related response after bacterial challenge in Astroides calycularis, a Mediterranean thermophilic coral

A worldwide increase in the prevalence of coral diseases and mortality has been linked to ocean warming due to changes in coral-associated bacterial communities, pathogen virulence, and immune system function. In the Mediterranean basin, the worrying upward temperature trend has already caused recurrent mass mortality events in recent decades. To evaluate how elevated seawater temperatures affect the immune response of a thermophilic coral species, colonies of Astroides calycularis were exposed to environmental (23 °C) or elevated (28 °C) temperatures, and subsequently challenged with bacterial lipopolysaccharides (LPS). Using immunolabeling with specific antibodies, we detected the production of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-kB), molecules involved in coral immune responses, and heat shock protein 70 (HSP70) activity, involved in general responses to thermal stress. A histological approach allowed us to characterize the tissue sites of activation (epithelium and/or gastroderm) under different experimental conditions. The activity patterns of the examined markers after 6 h of LPS stimulation revealed an up-modulation at environmental temperature. Under warmer conditions plus LPS-challenge, TLR4-NF-kB activation was almost completely suppressed, while constituent elevated values were recorded under thermal stress only. An HSP70 up-regulation appeared in both treatments at elevated temperature, with a significantly higher activation in LPS-challenge colonies. Such an approach is useful for further understanding the molecular pathogen-defense mechanisms in corals in order to disentangle the complex interactive effects on the health of these ecologically relevant organisms related to global climate change.

Ayurveda Approach towards Respiratory Illness in Children

Abstract: Preventable diseases such as pneumonia, diarrhoea, and other infections are the leading causes of morbidity in children, therefore each child's physical and emotional needs differ according to their age, personality, and developmental stage. 15% of children suffer from RRTIs. Predisposing variables include immune system inadequacies, anatomic and functional changes in the respiratory tract, air pollution exposure, and poor socioeconomic conditions. RRTIs are a prevalent disorder, especially in children under the age of six, and are usually caused by poor environmental conditions. 60% of patients had bacterial growth but RRIs begin as a viral respiratory tract infection and symptoms of infection for at least 10 days.i URTI is most common known cause of morbidity in children, which causes limiting daily activities and causing school absence.

Persistent epigenetic signals propel a senescence-associated secretory phenotype and trained innate immunity in CD34+ hematopoietic stem cells from diabetic patients

BackgroundDiabetes-induced trained immunity contributes to the development of atherosclerosis and its complications. This study aimed to investigate in humans whether epigenetic signals involved in immune cell activation and inflammation are initiated in hematopoietic stem/progenitor cells (HSPCs) and transferred to differentiated progeny.Methods and resultsHigh glucose (HG)-exposure of cord blood (CB)-derived HSPCs induced a senescent-associated secretory phenotype (SASP) characterized by cell proliferation lowering, ROS production, telomere shortening, up-regulation of p21 and p27genes, upregulation of NFkB-p65 transcription factor and increased secretion of the inflammatory cytokines TNFα and IL6. Chromatin immunoprecipitation assay (ChIP) of p65 promoter revealed that H3K4me1 histone mark accumulation and methyltransferase SetD7 recruitment, along with the reduction of repressive H3K9me3 histone modification, were involved in NFkB-p65 upregulation of HG-HSPCs, as confirmed by increased RNA polymerase II engagement at gene level. The differentiation of HG-HSPCs into myeloid cells generated highly responsive monocytes, mainly composed of intermediate subsets (CD14hiCD16+), that like the cells from which they derive, were characterized by SASP features and similar epigenetic patterns at the p65 promoter. The clinical relevance of our findings was confirmed in sternal BM-derived HSPCs of T2DM patients. In line with our in vitro model, T2DM HSPCs were characterized by SASP profile and SETD7 upregulation. Additionally, they generated, after myeloid differentiation, senescent monocytes mainly composed of proinflammatory intermediates (CD14hiCD16+) characterized by H3K4me1 accumulation at NFkB-p65 promoter.ConclusionsHyperglycemia induces marked chromatin modifications in HSPCs, which, once transmitted to the cell progeny, contributes to persistent and pathogenic changes in immune cell function and composition.

Thrombocytopenia Independently Leads to Changes in Monocyte Immune Function.

While platelets have well-studied hemostatic functions, platelets are immune cells that circulate at the interface between the vascular wall and white blood cells. The physiological implications of these constant transient interactions are poorly understood. Activated platelets induce and amplify immune responses, but platelets may also maintain immune homeostasis in healthy conditions, including maintaining vascular integrity and T helper cell differentiation, meaning that platelets are central to both immune responses and immune quiescence. Clinical data have shown an association between low platelet counts (thrombocytopenia) and immune dysfunction in patients with sepsis and extracorporeal membrane oxygenation, further implicating platelets as more holistic immune regulators, but studies of platelet immune functions in nondisease contexts have had limited study. We used in vivo models of thrombocytopenia and in vitro models of platelet and monocyte interactions, as well as RNA-seq and ATAC-seq (assay for transposase-accessible chromatin with sequencing), to mechanistically determine how resting platelet and monocyte interactions immune program monocytes. Circulating platelets and monocytes interact in a CD47-dependent manner to regulate monocyte metabolism, histone methylation, and gene expression. Resting platelet-monocyte interactions limit TLR (toll-like receptor) signaling responses in healthy conditions in an innate immune training-like manner. In both human patients with sepsis and mouse sepsis models, thrombocytopenia exacerbated monocyte immune dysfunction, including increased cytokine production. Thrombocytopenia immune programs monocytes in a manner that may lead to immune dysfunction in the context of sepsis. This is the first demonstration that sterile, endogenous cell interactions between resting platelets and monocytes regulate monocyte metabolism and pathogen responses, demonstrating platelets to be immune rheostats in both health and disease.

Restoring SRSF3 in Kupffer cells attenuates obesity-related insulin resistance.

In obesity, depletion of KCs expressing CRIg (complement receptor of the Ig superfamily) leads to microbial DNA accumulation, which subsequently triggers tissue inflammation and insulin resistance. However, the mechanism underlying obesity-mediated changes in KC complement immune functions is largely unknown. Using KC-specific deactivated Cas9 transgenic mice treated with guide RNA, we assessed the effects of restoring CRIg or the serine/arginine-rich splicing factor 3 (SRSF3) abundance on KC functions and metabolic phenotypes in obese mice. The impacts of weight loss on KC responses were evaluated in a diet switch mouse model. The role of SRSF3 in regulating KC functions was also evaluated using KC-specific SRSF3 knockout mice. Here, we report that overexpression of CRIg in KCs of obese mice protects against bacterial DNA accumulation in metabolic tissues. Mechanistically, SRSF3 regulates CRIg expression, which is essential for maintaining the CRIg+ KC population. During obesity, SRSF3 expression decreases, but it is restored with weight loss through a diet switch, normalizing CRIg+ KCs. KC SRSF3 is also repressed in obese human livers. Lack of SRSF3 in KCs in lean and obese mice decreases their CRIg+ population, impairing metabolic parameters. During the diet switch, the benefits of weight loss are compromised due to SRSF3 deficiency. Conversely, SRSF3 overexpression in obese mice preserves CRIg+ KCs and improves metabolic responses. Restoring SRSF3 abundance in KCs offers a strategy against obesity-associated tissue inflammation and insulin resistance by preventing bacterial DNA accumulation.

Alterations in metabolic pathways: a bridge between aging and weaker innate immune response.

Aging is a time-dependent progressive physiological process, which results in impaired immune system function. Age-related changes in immune function increase the susceptibility to many diseases such as infections, autoimmune diseases, and cancer. Different metabolic pathways including glycolysis, tricarboxylic acid cycle, amino acid metabolism, pentose phosphate pathway, fatty acid oxidation and fatty acid synthesis regulate the development, differentiation, and response of adaptive and innate immune cells. During aging all these pathways change in the immune cells. In addition to the changes in metabolic pathways, the function and structure of mitochondria also have changed in the immune cells. Thereby, we will review changes in the metabolism of different innate immune cells during the aging process.

The Impact of Aging on Multiple Sclerosis.

Multiple sclerosis (MS) is a chronic, immune-mediated demyelinating disorder of the central nervous system. Age is one of the most important factors in determining MS phenotype. This review provides an overview of how age influences MS clinical characteristics, pathology, and treatment. New methods for measuring aging have improved our understanding of the aging process in MS. New studies have characterized the molecular and cellular composition of chronic active or smoldering plaques in MS. These lesions are important contributors to disability progression in MS. These studies highlight the important role of immunosenescence and the innate immune system in sustaining chronic inflammation. Given these changes in immune function, several studies have assessed optimal treatment strategies in aging individuals with MS. MS phenotype is intimately linked with chronologic age and immunosenescence. While there are many unanswered questions, there has been much progress in understanding this relationship which may lead to more effective treatments for progressive disease.

Expression levels of key immune indicators and immune checkpoints in manganese-exposed rats

Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.

Single-Cell Sequencing Reveals Functional Alterations in Tuberculosis.

Despite its importance, the functional heterogeneity surrounding the dynamics of interactions between mycobacterium tuberculosis and human immune cells in determining host immune strength and tuberculosis (TB) outcomes, remains far from understood. This work now describes the development of a new technological platform to elucidate the immune function differences in individuals with TB, integrating single-cell RNA sequencing and cell surface antibody sequencing to provide both genomic and phenotypic information from the same samples. Single-cell analysis of 23990 peripheral blood mononuclear cells from a new cohort of primary TB patients and healthy controls enables to not only show four distinct immune phenotypes (TB, myeloid, and natural killer (NK) cells), but also determine the dynamic changes in cell population abundance, gene expression, developmental trajectory, transcriptomic regulation, and cell-cell signaling. In doing so, TB-related changes in immune cell functions demonstrate that the immune response is mediated through host T cells, myeloid cells, and NK cells, with TB patients showing decreased naive, cytotoxicity, and memory functions of T cells, rather than their immunoregulatory function. The platform also has the potential to identify new targets for immunotherapeutic treatment strategies to restore T cells from dysfunctional or exhausted states.

Status Epilepticus Following Labor in a Remote Area: A Case Report of Puerperal Sepsis

Background: Puerperal sepsis is one of the five leading causes of maternal mortality worldwide, commonly occurs in low to middle income countries. Higher incidence is observed in rural areas where diagnostic and therapeutic interventions may be limited.Case: A a 21-year-old woman who developed a fever, abdominal pain, and foul-smelling vaginal discharge five days after giving birth. The patient convulsed five times in total before being admitted. She was diagnosed with status epilepticus caused by sepsis-associated encephalopathy and puerperal sepsis, which was successfully treated with antibiotics and supportive care.Discussion: Pregnancy and the puerperium period involve significant changes in maternal physiology and immune function. The Society of Obstetric Medicine Australia and New Zealand (SOMANZ) has proposed Obstetric-modified quick sepsis related organ failure assessment (omqSOFA) for early recognition of maternal sepsis. An score of 2 or higher has predictive value for maternal sepsis.Conclusion: Early recognition, appropriate treatment, and close monitoring are crucial for improving outcomes in patients with puerperal sepsis.

Social anxiety disorder-associated gut microbiota increases social fear.

Social anxiety disorder (SAD) is a crippling psychiatric disorder characterized by intense fear or anxiety in social situations and their avoidance. However, the underlying biology of SAD is unclear and better treatments are needed. Recently, the gut microbiota has emerged as a key regulator of both brain and behaviour, especially those related to social function. Moreover, increasing data supports a role for immune function and oxytocin signalling in social responses. To investigate whether the gut microbiota plays a causal role in modulating behaviours relevant to SAD, we transplanted the microbiota from SAD patients, which was identified by 16S rRNA sequencing to be of a differential composition compared to healthy controls, to mice. Although the mice that received the SAD microbiota had normal behaviours across a battery of tests designed to assess depression and general anxiety-like behaviours, they had a specific heightened sensitivity to social fear, a model of SAD. This distinct heightened social fear response was coupled with changes in central and peripheral immune function and oxytocin expression in the bed nucleus of the stria terminalis. This work demonstrates an interkingdom basis for social fear responses and posits the microbiome as a potential therapeutic target for SAD.

Age-related changes in hematological biomarkers in common marmosets.

Researchers and veterinarians often use hematology and clinical chemistry to evaluate animal health. These biomarkers are relatively easy to obtain, and understanding how they change across healthy aging is critical to clinical care and diagnostics for these animals. We aimed to evaluate how clinical biomarkers from a chemistry profile and complete blood count (CBC)change with age in common marmosets (Callithrix jacchus). We assessed blood samples collected during routine physical exams at the Southwest National Primate Research Center and the University of Texas Health San Antonio marmoset colonies from November 2020-November 2021. We found that chemistry and CBC profiles varied based on facility, sex, and age. Significant changes in albumin, phosphorus/creatinine ratio, albumin/globulin ratio, amylase, creatinine, lymphocyte percent, hematocrit, granulocytes percent, lymphocytes, hemoglobin, red cell distribution width,and platelet distribution widthwere all reported with advancing age. Aged individuals also demonstrated evidence for changes in liver, kidney, and immune system function compared with younger individuals. Our results suggest there may be regular changes associated with healthy aging in marmosets that are outside of the range typically considered as normal values for healthy young individuals, indicating the potential need for redefined healthy ranges for clinical biomarkers in aged animals. Identifying animals that exhibit values outside of this defined healthy aging reference will allow more accurate diagnostics and treatments for aging colonies.

Analysis of Somatic Mutations in the TCGA-LIHC Whole Exome Sequence to Identify the Neoantigen for Immunotherapy in Hepatocellular Carcinoma.

There are numerous clinically proven methods for treating cancer worldwide. Immunotherapy has been used to treat cancer with significant success in the current studies. The purpose of this work is to identify somatically altered target gene neoantigens and investigate liver cancer-related immune cell interaction and functional changes for potential immunotherapy in future clinical trials. Clinical patient data from the Cancer Genome Atlas (TCGA) database were used in this investigation. The R maf utility package was used to perform somatic analysis. The 17-mer peptide neoantigens were extracted using an in-house Python software called Peptide.py. Additionally, the epitope analysis was conducted using NetMHCpan4.1 program. Neopeptide immunogenicity was assessed using DeepCNN-Ineo, and tumor immune interaction, association with immune cells, correlation, and survival analysis were assessed using the TIMER web server. Based on somatic mutation analysis, we have identified the top 10 driver genes (TP53, TNN, CTNNB1, MUC16, ALB, PCLO, MUC4, ABCA13, APOB, and RYR2). From the superfamily of 20 HLA (Human leukocyte antigens) allele epitopes, we discovered 5653 neopeptides. Based on T cell receptor face hydrophobic analysis, these neopeptides were subjected to immunogenicity investigation. A mutation linked to tumor growth may have an impact on immune cells. According to this study's correlation and survival analysis, all driver genes may function as immune targets for liver cancer. These genes are recognized to be immune targets. In the future, immune checkpoint inhibitors may be developed to prolong patient survival times and prevent hepatocellular carcinoma (HCC) through immunotherapy.

Novel evidence on iodoacetic acid-induced immune protein functional and conformational changes: Focusing on cellular and molecular aspects

Elevated levels of iodide occur in raw water in certain regions, where iodination disinfection byproducts are formed during chloramine-assisted disinfection of naturally iodide-containing water. Iodoacetic acid (IAA) is one of the typical harmful products. The mechanisms underlying IAA-induced immunotoxicity and its direct effects on biomolecules remained unclear in the past. Cellular, biochemical, and molecular methods were used to investigate the mechanism of IAA-induced immunotoxicity and its binding to lysozyme. In the presence of IAA, the cell viability of coelomocytes was significantly reduced to 70.8 %, as was the intracellular lysozyme activity. Upon binding to IAA, lysozyme underwent structural and conformational changes, causing elongation and unfolding of the protein due to loosening of the backbone and polypeptide chains. IAA effectively quenched the fluorescence of lysozyme and induced a reduction in particle sizes. Molecular docking revealed that the catalytic residue, Glu 35, which is crucial for lysozyme activity, resided within the docking range, suggesting the preferential binding of IAA to the active site of lysozyme. Moreover, electrostatic interaction emerged as the primary driving force behind the interaction between IAA and lysozyme. In conclusion, the structural and conformational changes induced by IAA in lysozyme resulted in impaired immune protein function in coelomocytes, leading to cellular dysfunction.

Mathematical Modeling of the Lethal Synergism of Coinfecting Pathogens in Respiratory Viral Infections: A Review.

Influenza A virus (IAV) infections represent a substantial global health challenge and are often accompanied by coinfections involving secondary viruses or bacteria, resulting in increased morbidity and mortality. The clinical impact of coinfections remains poorly understood, with conflicting findings regarding fatality. Isolating the impact of each pathogen and mechanisms of pathogen synergy during coinfections is challenging and further complicated by host and pathogen variability and experimental conditions. Factors such as cytokine dysregulation, immune cell function alterations, mucociliary dysfunction, and changes to the respiratory tract epithelium have been identified as contributors to increased lethality. The relative significance of these factors depends on variables such as pathogen types, infection timing, sequence, and inoculum size. Mathematical biological modeling can play a pivotal role in shedding light on the mechanisms of coinfections. Mathematical modeling enables the quantification of aspects of the intra-host immune response that are difficult to assess experimentally. In this narrative review, we highlight important mechanisms of IAV coinfection with bacterial and viral pathogens and survey mathematical models of coinfection and the insights gained from them. We discuss current challenges and limitations facing coinfection modeling, as well as current trends and future directions toward a complete understanding of coinfection using mathematical modeling and computer simulation.

Disease activity is associated with changes in the innate immune function in patients with systemic lupus erythematosus.

To address the relationship between systemic lupus erythematosus (SLE) disease activity and the functional parameters of the innate immunity. We evaluated a cohort of 26 adult SLE patients and 10 sex and age-paired healthy donors. When the patients had a disease flare (baseline) and when they achieve clinical response (follow-up), we assessed the systemic lupus erythematosus disease activity index 2K (SLEDAI 2K) and the following parameters with flow cytometry and confocal microscopy: monocyte subsets, their expression of TLR2, phagocytic monocytes and neutrophils using the pHrodo Red E. coli BioParticles, the respiratory burst with 123-dihydrorhodamine in neutrophils, and the spontaneous and lipopolysaccharide (LPS)-induced production of neutrophil extracellular traps (NETs). We used the Wilcoxon test to compare the paired medians with interquartile range (IQR) and the Mann-Whitney U test for independent medians. To assess the effect of prednisone and SLEDAI 2K on the mentioned parameters, we applied a generalized mixed linear model. Twenty-three patients (88.4%) were women. The SLEDAI 2K was higher at baseline 8 (6-14) in comparison to that at follow-up (6 (4-8), P = 0.028). At baseline, SLE patients had a decreased percentage of intermediate monocytes, a higher expression of TLR2 in total monocytes, increased phagocytosis in monocytes and neutrophils, a decreased respiratory burst intensity, and an increased production of NETs. In the mix model, the SLEDAI 2K was the main factor influencing these functional innate immune parameters. Disease activity regulates the innate immune function in SLE which may contribute to the clinical features and infection predisposition. Key points • This is the first cohort study addressing the effect of disease activity and prednisone use on the innate immune function of lupus patients. • Our results show that the disease activity is a key regulator of the respiratory burst, phagocytosis, and the production of neutrophil extracellular traps. • Also, we observed a differential proportion of monocyte subsets according to SLE disease activity. • We consider that our manuscript contributes to the evidence addressing the intrinsic immune abnormalities of patients with SLE regardless of the use of immunosuppressants and set the bases for new research work considering the disease activity as an element to decide the prescription and duration of antibiotic prophylaxis in SLE patients, which is of interest to all rheumatologists.

Seasonal changes in diet, immune function, and oxidative stress in three passerines inhabiting a Mediterranean climate.

Oxidative status and immune function are energy-demanding traits closely linked to diet composition, particularly resource availability and nutritional value. In seasonal environments, nutrient availability and diet quality fluctuate, potentially influencing these traits. However, limited evidence exists regarding these dietary effects on immune function in seasonal environments. In this study, we employed stable isotope analysis to assess the impact of seasonal changes in niche width and trophic level (i.e., δ15N) on two immune variables (hemolysis and hemagglutination scores) and two oxidative status parameters (lipid peroxidation and total antioxidant capacity) in three passerine species: Zonotrichia capensis (omnivorous), Troglodytes aedon (insectivorous), and Spinus barbatus (granivorous). We found that hemolysis scores varied seasonally in Z. capensis, with higher values in winter compared to summer. Total antioxidant capacity (TAC) also increased during the winter in Z. capensis and S. barbatus. The isotopic niche width for Z. capensis and S. barbatus was smaller in winter than in summer, with the omnivorous species exhibiting a decrease in δ15N. Despite the seasonal shifts in ecological and physiological traits in Z. capensis, we identified no correlation between immune response and TAC with trophic level. In contrast, in the granivorous S. barbatus, the lower trophic level resulted in an increase in TAC without affecting immunity. Our findings revealed that dietary shifts do not uniformly impact oxidative status and immune function across bird species, highlighting species-specific responses to seasonal changes. This underscores the importance of integrating ecological and evolutionary perspectives when examining how diet shapes avian immunity and oxidative balance.

PCSK9-inhibitor therapy leads to changes in immune cell gene expression and function: A subset analysis of the PACMAN-AMI trial

Abstract Introduction The PACMAN-AMI trial showed a significant reduction of plaque atheroma volume by alirocumab on top of high-intensity statin therapy as compared to placebo in 265 patients undergoing serial multi-vessel imaging after acute myocardial infarction (AMI). Neutrophils and the formation of neutrophil extracellular traps (NETs) have been implicated in the development and progression of atherosclerosis. High levels of low-density lipoprotein (LDL) have been associated with neutrophil activation. Objectives This study aimed to determine the influence of aggressive LDL-lowering on neutrophil activation, and immune cell gene expression of pro-inflammatory markers in a subset of the PACMAN-AMI cohort. Methods Neutrophils and peripheral blood mononuclear cells (PBMC) of 38 patients were isolated by serial density-gradient centrifugation to assess relative gene expression of IL-1b, IL-6, TNFa, X-box binding protein (XBP) 1, caspase 1 (CASP1), and NLRP3 by quantitative PCR. Neutrophils were stimulated to undergo NET formation using a calcium ionophore in the presence or absence of pro-protein convertase subtilisin/kexin type 9 (PCSK9), detecting the release of double-stranded (ds)DNA. Plasma samples were screened for dsDNA, citrullinated histone H3, neutrophil elastase, and myeloperoxidase. Healthy controls (n=30) were recruited during routine check-ups in a health and prevention center. Results After one year of double-blind injections, the probability to undergo NET formation in vitro was still higher in AMI patients than in healthy controls. Considering randomized treatment, only patients injected with alirocumab showed significantly higher NET release than controls. Additional stimulation with the alirocumab target PCSK9 could reduce NET formation in all cohorts. This effect was significantly higher in patients treated with alirocumab. Relative gene expression of CASP1, IL-1b, IL-6, and XBP 1 was higher in patients treated with alirocumab. There was no difference in plasma NET markers comparing healthy controls and both treatment arms. Conclusion Our data indicate that PCSK9 might have effects beyond its role in cholesterol metabolism influencing immune cell activation, which could mask effects of LDL lowering. Treatment does not directly translate to higher plasma NET levels without an additional inflammatory stimulus disrupting the steady state.

402 Awardee Talk: Stress-Induced Dna Methylation Changes and Their Implications in Livestock Production

Abstract It is well known that pre- and post-natal stressors can impact livestock phenotype and performance. However, less is known about the molecular mechanisms responsible for the changes observed in individuals exposed to stress. A proposed mechanism is epigenetic modifications, such as DNA methylation (DNAm). Epigenetic marks are considered a bridge between the environment and genetics because the marks shift in response to environmental stimuli. Stress induced alterations of DNAm can result in changes in gene expression which could be the driver behind altered phenotype. “Omic” technologies have allowed the study of how DNAm patterns change in response to stressors in livestock species. Stressors such as weaning, transportation, and heat stress have altered DNAm patterns. These changes in methylation patterns have been associated with changes in immune function, growth, and behavior. Prenatal stressors have also modified DNAm patterns within the offspring, with some differences persisting later in life. These stress induced DNAm alterations can be transgenerational, potentially affecting livestock productivity and health over multiple generations. Not all alterations are negative; certain stress-induced modifications could allow animals to adapt better to stressors and changing conditions. These marks may indicate exposure of the animal to stress and the possible long-term effects on productivity. There is potential for using methylation patterns as a noninvasive way to monitor stress levels and assess animal welfare. Understanding how the methylome responds to stressors and how it contributes to performance will be beneficial for future selection decisions. More research is needed to identify management practices that might mitigate the negative impacts of stress induced DNAm changes and how the industry can take advantage of the role DNAm has in adapting to stressors and new environments. The epigenome will likely play a critical role in the livestock industry's future as the climate shifts and consumer demands focus more on animal welfare.

28 On-Farm Rapid Test to Assess Immunological Health of Young Pigs

Abstract Immunological competence is important for young pig survivability. A rapid on-farm test of immunological status may be a tool to help with early identification of sick animals. A new immunological test uses gold nanoparticle technology (D2Dx) to detect changes in serum proteins, particularly IgG and was evaluated as a potential on-farm measure of immunological health of pigs born during a farm level Porcine Respiratory Reproductive Syndrome (PRRS) outbreak. Up to three piglets from each litter in 2 farrowing groups (28 days apart) were selected for serial blood sampling and monitoring of body weight. Group 1 (n = 13 sows) experienced the PRRS outbreak approximately 14 days before farrowing and Group 2 (n = 15) approximately 40 days before farrowing. Attempts were made to select one piglet from each of 3 general categories [small (< 1.0 kg), average (1.1 – 1.6 kg), heavy (>1.6 kg)] from each litter. Serum samples were collected at day 2 and 15 of age from each piglet and serum IgG concentration and D2Dx ratio were assessed. Serum immunocrit at day 2 was also completed. Daily animal care of piglets and sows followed standard barn protocols. No creep feed was provided, sows were fed ad libitum, and cross-fostering was limited. Stillborn rate and preweaning death loss was approximately 70% in Group 1 and 35% in Group 2. Birth weight was similar between Group 1 and 2 litters (1.4 ± 0.3 kg). However, body weight gain to day 15 was 1.7 ± 0.95 kg and 2.7 ± 1.1 kg for piglets from Group 1 and 2, respectively, which may be due to timing of the PRRS outbreak. The D2Dx ratio declined from day 2 to 15 (0.029 vs -0.002) in both groups and was significantly reduced in Group 2 pigs (P < 0.001). A lower ratio suggests a stronger type 2 immune response and has been associated with decreased overall immunity in cattle, humans, and rodents. The D2Dx ratio was negatively correlated (r = -0.58) with BW gain in Group 1 pigs and positively correlated (r = 0.36) with gain in Group 2 pigs. Both immunocrit (day 2) and IgG (d15) were greater in Group 1 pigs than Group 2 (P < 0.01). There was a no relationship between birth weight and day 2 serum immunocrit (R2 = 0.06) or day 2 D2Dx (R2 = 0.01). There was no relationship between serum IgG and D2Dx at d15. The PRRS disease activity impacts immunocrit and serum IgG measures in the neonatal pig. The D2Dx ratio was not strongly related to piglet immunological status under disease conditions; however, the stronger type 2 immune response may be reflective of positive changes in piglet immune function and the response to maternal PRRS antibodies in milk.