Immunological Stress Research Articles

Plasma Cortisol and Thyroid Hormone Profile in Theileria equi Affected Horses

Equine theileriosis caused by Theileria equi is an endemic disease in most of the countries. The latently infected animals may exhibit low performance following physical, immunological or mental stress due to the flare-up of underlying parasitemia leading to clinical form of the disease. In the present study, 72 horses were screened for T. equi by using polymerase chainm reaction based on equine merozoite antigen-5 and 6, which revealed 25 to be positive for theileriosis. Further study was conducted to assess the cortisol and thyroid hormone (T3 and T4) levels in healthy (n=47) and in T. equi infected (n=25) horses. In horses positive for T. equi, there was significant increase (p less than 0.05) in cortisol (42.80±0.69 vs. 24.44± 0.12 ng/ml) and T4 level (47.56±4.06 vs. 38.14±2.40 ng/ml) with significant reduction (p less than 0.01) in T3 level (0.44±0.13 vs. 1.20±0.19 ng/ml) when compared to the healthy group. This may be the first report revealing that theileriosis infected horses are under stress due to the involvement of endocrine system as well as metabolic pathways.

Metabolic Reprogramming of Myeloid Cells in Response to Factors of “Emergency” Myelopoiesis By Myeloid-Specific PD-1 Ablation, Regulates Myeloid Lineage Fate Commitment and Anti-Tumor Immunity

PD-1 is a T cell inhibitor for which blocking agents have achieved success as anti-cancer therapeutics. The current view is that cancer limits host immune responses by upregulating PD-L1 in the tumor microenvironment (TME) thereby causing PD-1 ligation and inactivation of CD8+ Teff cells. However, PD-L1 expression in the TME does not always correlate with therapeutic response. Thus, the mechanism(s) by which PD-1 blockade reverses compromised anti-tumor immunity are poorly understood. The rapid increase in hematopoietic cell output that occurs in response to immunologic stress is known as emergency myelopoiesis. Low-level stimulation by cancer-generated factors induces modest but continuous expansion of myeloid progenitors (MP) (common myeloid progenitors (CMP) and granulocyte/macrophage progenitors (GMP)) albeit with hindered differentiation, leading to output of tumor-promoting myeloid-derived suppressor cells (MDSCs). We determined that myeloid cells expanding during cancer-driven emergency myelopoiesis in tumor-bearing mice express PD-1 and PD-L1. Using PD-1 KO mice we found that PD-1 deletion prevented the accumulation of GMP and stimulated the output of Ly6Chi effector monocytes, macrophages and dendritic cells (DC). To determine whether these outcomes were mediated by a myeloid-intrinsic impact of PD-1 ablation or by the effects of PD-1neg T cells on myeloid cells, we generated mice with conditional targeting of the Pdcd1 gene (PD-1f/f) and selectively eliminated PD-1 in myeloid cells (PD-1f/fLysMcre) or T cells (PD-1f/fCD4cre). Myeloid-specific, but not T cell-specific PD-1 ablation, prevented the accumulation of GMP while promoting the output of effector-like myeloid cells expressing CD80, CD86, CD16/32 (FcRII/III) and CD88 (C5aR). Myeloid cells with PD-1 ablation had elevated expression of IRF8 that drives monocyte and DC differentiation and decreased expression of the MDSC hallmark markers IL-4R, CD206, ARG1 and CD38. Nutrient utilization has a decisive role on the fate of hematopoietic progenitors (HP) and MP. Stemness and pluripotency are regulated by maintenance of glycolysis whereas switch to mitochondrial metabolism is associated with differentiation. To examine whether PD-1 ablation affected these metabolic proceces, bone marrow (BM) from PD-1f/f and PD-1f/fLysMcre mice was cultured with G-CSF/GM-CSF/IL-6, key drivers of emergency myelopoiesis. MP differentiation was documented by decrease of Linneg and increase of Linpos cells, which was more prominent in PD-1f/fLysMcre BM cultures. This coincided with increase of CD45+CD11b+ and dominance of Ly6C+ monocytic cells consistent with a cell-intrinsic mechanism of monocytic lineage commitment. PD-1f/fLysMcre MP had elevated mTORC1, Erk1/2 and Stat1 activation, and enhanced glucose uptake and mitochondrial biogenesis. Bioenergetics studies showed robust development of a mitochondrial-dominant profile, consistent with metabolism-driven enhanced differentiation of MP. Mass spectrometry revealed enhanced intermediates of glycolysis, PPP and TCA cycle, but the most prominent difference was the increased cholesterol. Because mTORC1 signaling, which was enhanced in PD-1f/fLysMcre MP, activates de novo lipid and cholesterol synthesis via SREBP1, we examined the mevalonate pathway of cholesterol synthesis. mRNA for genes mediating cholesterol synthesis and uptake was increased whereas mRNA for genes mediating cholesterol metabolism was decreased. Cholesterol induces a proinflammatory program in myeloid cells, drives differentiation of monocytes, macrophages and DC and promotes antigen-presenting function. We examined how such changes in myeloid cells might affect the function of T cells, which are key anti-tumor mediators. Compared to tumor-bearing PD-1f/f mice, PD-1f/fLysMcre tumor-bearers had no quantitative T cell differences but had an increase in IFNγ- IL-17-, and IL-10-expressing CD8+ Teff-mem and IL-2-expressing Tcentral-mem cells, consistent with superior functionality. These changes correlated with enhanced anti-tumor protection despite preserved PD-1 expression in T cells. Our findings reveal a previously unidentified role of PD-1 in metabolism-driven myeloid cell lineage fate commitment and differentiation and suggest that switch to effector myeloid cells might be a key mechanism by which PD-1 blockade mediates systemic anti-tumor immunity. DisclosuresNo relevant conflicts of interest to declare.

Postural orthostatic tachycardia syndrome: clinical presentation, aetiology and management.

Postural orthostatic tachycardia syndrome (POTS) is a variant of cardiovascular autonomic disorder characterized by an excessive heart rate increase on standing and orthostatic intolerance. POTS affectsyounger individuals 15-45years old with a distinct female predominance (≈80%). The prevalence ranges between 0.2% and 1.0% in developed countries. The onset of POTS is typically precipitated by immunological stressors such as viral infection, vaccination, trauma, pregnancy, surgery or psychosocial stress. The most common complaints are dizziness, weakness, rapid heartbeat and palpitation on standing. Moreover, patients often report physical deconditioning and reduced exercise capacity as well as headache, 'brain fog', dyspnoea, gastrointestinal disorders and musculoskeletal pain. The aetiology of POTS is largely unknown and three main hypotheses include an autoimmune disorder, abnormally increased sympathetic activity and catecholamine excess, and sympathetic denervation leading to central hypovolaemia and reflex tachycardia. The golden standard for POTS diagnosis is head-up tilt test with a non-invasive beat-to-beat haemodynamic monitoring. Although long-term prognosis of POTS is poorly explored, around 50% of patients spontaneously recover within 1-3years. After the diagnosis has been established, patient should be thoroughly educated about non-pharmacological measures alleviating the symptoms. Exercise training may be very effective and counteract deconditioning. In more symptomatic patients, different drugs directed at controlling heart rate, increasing peripheral vasoconstriction and intravascular volume can be tested. However, the overall effects of pharmacological therapy are modest and the most affected patients remain handicapped. Future efforts should focus on better understanding of POTS pathophysiology and designing randomized controlled trials for selection of more effective therapy.

Molecular characterization of big-belly seahorse (Hippocamus abdominalis) arachidonate 5-lipoxygenase (HaALOX5): First evidence of an immune defensive role by induced immunological stress in teleost

Arachidonate 5-lipoxygenase (ALOX5) is an essential enzyme for the biosynthesis of leukotrienes, which are pro-inflammatory and anti-inflammatory mediators. In this study, the ALOX5 paralog of the big-belly seahorse (Hippocampus abdominalis; HaALOX5) was identified from our transcriptome database, and then molecularly and functionally characterized to determine its oxygenation capability and expression under pathogenic stress. The coding sequence of HaALOX5 consisted of 2025 bp and encoded a protein of 674 amino acids in length. Sequence and phylogenetic tree analysis of HaALOX5 revealed a close relationship with its corresponding teleost HaALOX5 counterparts. Structure prediction detected an N-terminal regulatory C2-like domain and a C-terminal catalytic domain, which are the two main functional domains in ALOX5 enzymes. Quantitative PCR showed that HaALOX5 was expressed in all the analyzed tissues at different magnitudes. The highest expression was detected in the intestine and stomach. In blood cells, the liver and the intestine, HaALOX5 transcripts were significantly elevated at many post injection time points, when immune challenged with lipopolysaccharide, polyinosinic:polycytidylic acid, and Streptococcus iniae, indicating its contribution to post immune defense mechanisms in the seahorse.

The effects of a therapeutic formalin bath on selected immunological and oxidative stress parameters in common carp (Cyprinus carpio)

Formalin is commonly used as a component of antiparasitic baths in fisheries. In this study the impact of this bath on the immune profile and oxidative stress parameters was evaluated. A formalin bath was prepared in the concentration of 185.3 mg L−1 (0.17 mL L−1) at a temperature of 20 °C. A total of 96 common carp Cyprinus carpio (Linnaeus, 1758) individuals were immersed in this bath for 60 min. The effects were monitored immediately, and then after 24, 48 h and 10 days following the treatment. The study revealed the most effects 10 days after the treatment, when we observed the decrease of lysozyme in skin mucus, the decrease of anti-inflammatory cytokine transforming growth factor beta in gill tissue and increase of interleukin 10 in cranial kidney tissue. The pro-inflammatory cytokine interleukin 1b showed an increase in gill tissue immediately after the bath and the increase in glutathione peroxidase in gill tissue was also observed 24 h and 10 days after bath treatment. The other investigated parameters did not show any significant changes. In conclusion, even though the formalin bath elevated some parameters as mentioned above, formalin used in the bath is probably safe as an antiparasitic treatment of fish.

Interactions between polycyclic aromatic hydrocarbons and epoxide hydrolase 1 play roles in asthma.

Asthma, as one of the most common chronic diseases in children and adults, is a consequence of complex gene-environment interactions. Polycyclic aromatic hydrocarbons (PAHs), as a group of widespread environmental organic pollutants, are involved in the development, triggering and pathologic changes of asthma. Various previous studies reported the critical roles of PAHs in immune changes, oxidative stress and environment-gene interactions of asthma. EPHX1 (the gene of epoxide hydrolase 1, an enzyme mediating human PAH metabolism) had a possible association with asthma by influencing PAH metabolism. This review summarized that (1) the roles of PAHs in asthma-work as risk factors; (2) the possible mechanisms involved in PAH-related asthma-through immunologic and oxidative stress changes; (3) the interactions between PAHs and EPHX1 involved in asthma-enzymatic activity of epoxide hydrolase 1, which affected by EPHX1 genotypes/SNPs/diplotypes, could influence human PAH metabolism and people's vulnerability to PAH exposure. This review provided a better understanding of the above interactions and underlying mechanisms for asthma which help to raise public's concern on PAH control and develop strategies for individual asthma primary prevention.

The blood–brain barrier, TWEAK, and neuropsychiatric involvement in human systemic lupus erythematosus and primary Sjögren’s syndrome

A prevailing hypothesis for neuropsychiatric involvement in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome is that brain reactive autoantibodies enter the brain through a disrupted blood-brain barrier. Our aim was to investigate whether TNF-like weak inducer of apoptosis (TWEAK) plays a role in cerebral involvement in human SLE and primary Sjögren's syndrome, and whether an impaired blood-brain barrier is a prerequisite for neuropsychiatric manifestations. TWEAK was measured in the cerebrospinal fluid and serum and compared with markers of blood-brain barrier permeability (Q-albumin and MRI contrast-enhanced lesions) and S100B, an astrocyte activation marker in 50 SLE and 52 primary Sjögren's syndrome patients. Furthermore, we estimated the general intrathecal B-cell activation (IgG index), measured anti-NR2 antibodies in cerebrospinal fluid, and explored whether these variables were associated with neuropsychiatric manifestations. No associations were found between TWEAK in the cerebrospinal fluid or serum and neuropsychiatric manifestations in SLE nor in primary Sjögren's syndrome patients. Furthermore, no associations were found between neuropsychiatric manifestations and indicators of blood-brain barrier integrity or astroglial activity. Anti-NR2 antibodies were associated with impaired visuospatial processing (odds ratio 4.9, P = 0.03) and motor functioning (odds ratio 6.0, P = 0.006). No clinical neuropsychiatric manifestations could be attributed to impaired integrity of the blood-brain barrier, or to TWEAK levels in cerebrospinal fluid or serum in either patient group. The TWEAK concentration was considerably higher in the cerebrospinal fluid than in blood, which indicates intrathecal production. We hypothesize that increased TWEAK and S100B result from immunological stress caused by brain-reactive antibodies produced by brain residing immune cells.

Effects of lipopolysaccharide (LPS) challenge on antioxidant capability of broiler chickens

This study was designed to investigate the effects of lipopolysaccharide (LPS) challenge on antioxidant capability (superoxide dismutase, SOD; catalase, CAT; glutathione peroxidase, GPX; and reduced glutathione to oxidized glutathione, GSH/GSSG) and induce the model of immunological stress in broiler chickens. Day-old, yellowfeathered broilers (140) were randomly assigned to 2 treatments with 7 replicates of 10 chicks each. At day 21, 23, 25 and 27, chicks were injected with LPS and blood samples were collected after 24 h. Chicks (2) from each replicate were killed, and liver and jejunum samples were collected. The activities and gene expression of SOD, CAT, and GPX, were determined. The results showed that LPS challenge reduced serum SOD at day 22 and 26, serum CAT at day 24, 26, and 28, and serum GPX at day 26. LPS challenge decreased liver SOD, liver GPX, liver GSH/GSSG ratio at day 26 and 28. LPS challenge also decreased jejunum SOD at day 26, and jejunum CAT, GPX and GSH/GSSG ratio at day 26 and 28.The expressions of liver CAT, liver GPX1, and jejunum SOD1 were down regulated at day 26. The expressions of jejunum CAT, and jejunum GPX1 were down regulated at day 26. Meanwhile, LPS reduced the expression of liver SOD1 at day 22 and the expression of jejunum GPX1 at day 28. In conclusion, three times of LPS challenge could result in serious oxidative damage and induce immune stress model.

Deciphering the Contributions of CRH Receptors in the Brain and Pituitary to Stress-Induced Inhibition of the Reproductive Axis.

Based on pharmacological studies, corticotropin-releasing hormone (CRH) and its receptors play a leading role in the inhibition of the hypothalamic–pituitary–gonadal (HPG) axis during acute stress. To further study the effects of CRH receptor signaling on the HPG axis, we generated and/or employed male mice lacking CRH receptor type 1 (CRHR1) or type 2 (CRHR2) in gonadotropin-releasing hormone neurons, GABAergic neurons, or in all central neurons and glia. The deletion of CRHRs revealed a preserved decrease of plasma luteinizing hormone (LH) in response to either psychophysical or immunological stress. However, under basal conditions, central infusion of CRH into mice lacking CRHR1 in all central neurons and glia, or application of CRH to pituitary cultures from mice lacking CRHR2, failed to suppress LH release, unlike in controls. Our results, taken together with those of the earlier pharmacological studies, suggest that inhibition of the male HPG axis during acute stress is mediated by other factors along with CRH, and that CRH suppresses the HPG axis at the central and pituitary levels via CRHR1 and CRHR2, respectively.

Autophagy in Paracoccidioides brasiliensis under normal mycelia to yeast transition and under selective nutrient deprivation.

Paracoccidioides spp. is a thermally dimorphic fungus endemic to Latin America and the etiological agent of paracoccidioidomycosis (PCM), a granulomatous disease acquired through fungal propagule inhalation by its mammalian host. The infection is established after successful mycelia to yeast transition in the host pulmonary alveoli. The challenging environment inside the host exposes the fungus to the need of adaptation in order to circumvent nutritional, thermal, oxidative, immunological and other stresses that can directly affect their survival. Considering that autophagy is a response to abrupt environmental changes and is induced by stress conditions, this study hypothesizes that this process might be crucially involved in the adaptation of Paracoccidioides spp. to the host and, therefore, it is essential for the proper establishment of the disease. By labelling autophagous vesicles with monodansylcadaverine, autophagy was observed as an early event in cells during the normal mycelium to yeast transition, as well as in yeast cells of P. brasiliensis under glucose deprivation, and under either rapamycin or 3-methyladenine (3-MA). Findings in this study demonstrated that autophagy is triggered in P. brasiliensis during the thermal-induced mycelium to yeast transition and by glucose-limited conditions in yeasts, both of which modulated by rapamycin or 3-MA. Certainly, further genetic and in vivo analyses are needed in order to finally address the contribution of autophagy for adaptation. Yet, our data propose that autophagy possibly plays an important role in Paracoccidioides brasiliensis virulence and pathogenicity.

Dietary vitamin D3 supplementation protects laying hens against lipopolysaccharide-induced immunological stress

BackgroundThe effects of vitamin D on the immune function of laying hens are not well understood. This study investigated the effects of vitamin D3 (VD3) on laying performance and immunological functions in laying hens under Escherichia coli lipopolysaccharide (LPS) challenge.MethodsIn experiment one, 360 Jinghong-1 strain layers (32 weeks) were randomly divided into four groups with six replicates per group and 15 hens per replicate. Hens were fed a basal diet supplemented with different levels of VD3 (0; 500; 1500; or 3000 IU VD3/kg of diet) for 10 weeks to determine laying performance, egg quality, and other parameters. In experiment two, 24 Jinghong laying hens (32 weeks) were fed basal diets with either 0 or 3000 IU VD3/kg of diet. After 10 weeks of feeding, six hens from each treatment were injected intravenously with 8 mg/kg of body weight of either LPS or saline. Blood and spleen samples were obtained for immune parameter analysis 4 h after injection.ResultsVD3 deficiency reduced egg production and egg quality; in addition, feed intake and feed-to-egg ratio increased. No significant differences were observed in these parameters except eggshell strength between dietary VD3 supplemental levels at 500; 1500; and 3000 IU VD3/kg of diet. VD3 deficiency increased serum hormone (calcitonin, parathyroid hormone, estradiol, and progesterone) and cytokine (IL-6, IL-10) levels, the ratio of IFN-γ to IL-4, myeloperoxidase activity and total IgG content in the serum, and upregulated the blood CD3+ T cell population. Splenic retinoid X receptor (RXR), nuclear factor-κB (NF-κB), inducible nitric oxide synthase (iNOS), and polymeric immunoglobulin receptor (pIgR) gene mRNA levels were upregulated in VD3-deficienct hens. VD3 deficiency significantly reduced serum Follicle stimulating hormone (FSH) and Luteinizing hormone (LH) concentrations and the number of CD4+CD25+ T cells in the blood. These changes were completely normalized by VD3 sufficiency. LPS reduced serum LH concentration, splenic lysozyme, and pIgR gene mRNA levels. LPS induced an increase in total serum IgM levels and the percentage of CD8+ T cells in the blood. The changes were completely reversed by VD3 addition.ConclusionVD3 supplementation could protect laying hens not only from VD3 deficiency but also from immunological stress.

A Comparison between Post-Operative Analgesia after Intrathecal Injection of Nalbuphine versus Fentanyl as an Adjuvent to Bupivacaine after Cesarean Section

Background: one of the primary aims of anesthesia is to alleviate the patient’s pain and agony, by permitting the performance of surgical procedures without any discomfort. Relief of postoperative pain has gained real importance in recent years considering the central, peripheral and immunological stress response to tissue injury. Any expertise acquired in this field should be extended into the postoperative period, which is the period of severe, intolerable pain requiring attention. So there is a need for extended analgesia without any side effects to achieve this goal. The use of opioids in intrathecal or epidural anesthesia has become popular to optimize postoperative analgesia. However, opioid-induced side effects, such as respiratory depression, nausea, vomiting, urinary retention and pruritus, limit their use. Aim of the Work: the purpose of this study was to assess the postoperative analgesic requirements and the spinally mediated analgesic effects of intrathecal nalbuphine as an adjunct to intrathecal bupivacaine after cesarean section in comparison to intrathecal bupivacaine plus fentanyl. Patients and Methods: eighty female patients came to Demerdash Hospital for cesarean delivery, they were randomly allocated into two equal groups (40 patients) group F and group N. Group F: Bupivacaine-Fentanyl: Patients received an intrathecal injection of 2 ml of 0.5% heavy (hyperbaric) bupivacaine plus 0.5 ml (25 µg) fentanyl. Group N: Bupivacaine-Nalbuphine: Patients received an intrathecal injection of 2 ml of 0.5% heavy (hyperbaric) bupivacaine plus 0.5 ml (0.8 mg) Nalbuphine. Results: the addition of a small dose of nalbuphine or fentanyl to bupivacaine in spinal anesthesia moderately prolonged the time of postoperative analgesia, while the duration of analgesia was more prolonged and the adverse effects were minimal with the group of nalbuphine, our result shows no significant difference, but shows significant difference in the More rapid onset of sensory block with Fentanyl than with Naluphine, more rapid Regression time to S1 dermatome with Fentanyl than with Naluphine, the duration of motor block is shorter with Fentanyl than with Naluphine, patients receive rescue analgesia 6 h postoperatively is fewer with Nalpuphine than Fentanyl. Conclusion: more rapid onset of motor block in fentanyl group than in nalbuphine group, more rapid onset of sensory block with Fentanyl than with Naluphine, more rapid regression time to S1 dermatome with Fentanyl than with Naluphine.

Paternal sepsis induces alterations of the sperm methylome and dampens offspring immune responses\u2014an animal study

BackgroundSepsis represents the utmost severe consequence of infection, involving a dysregulated and self-damaging immune response of the host. While different environmental exposures like chronic stress or malnutrition have been well described to reprogram the germline and subsequently offspring attributes, the intergenerational impact of sepsis as a tremendous immunological stressor has not been examined yet.MethodsPolymicrobial sepsis in 12-week-old male C57BL/6 mice was induced by cecal ligation and puncture (CLP), followed by a mating of the male survivors (or appropriate sham control animals) 6 weeks later with healthy females. Alveolar macrophages of offspring animals were isolated and stimulated with either LPS or Zymosan, and supernatant levels of TNF-α were quantified by ELISA. Furthermore, systemic cytokine response to intraperitoneally injected LPS was assessed after 24 h. Also, morphology, motility, and global DNA methylation of the sepsis survivors’ sperm was examined.ResultsComparative reduced reduction bisulfite sequencing (RRBS) of sperm revealed changes of DNA methylation (n = 381), most pronounced in the intergenic genome as well as within introns of developmentally relevant genes. Offspring of sepsis fathers exhibited a slight decrease in body weight, with a more pronounced weight difference in male animals (CLP vs. sham). Male descendants of sepsis fathers, but not female descendants, exhibited lower plasma concentrations of IL-6, TNF-alpha, and IL-10 24 h after injection of LPS. In line, only alveolar macrophages of male descendants of sepsis fathers produced less TNF-alpha upon Zymosan stimulation compared to sham descendants, while LPS responses kept unchanged.ConclusionWe can prove that male—but surprisingly not female—descendants of post-sepsis fathers show a dampened systemic as well as pulmonary immune response. Based on this observation of an immune hypo-responsivity, we propose that male descendants of sepsis fathers are at risk to develop fungal and bacterial infections and might benefit from therapeutic immune modulation.

Standardized Assessment of Resistance Training-Induced Subjective Symptoms and Objective Signs of Immunological Stress Responses in Young Athletes.

From a health and performance-related perspective, it is crucial to evaluate subjective symptoms and objective signs of acute training-induced immunological responses in young athletes. The limited number of available studies focused on immunological adaptations following aerobic training. Hardly any studies have been conducted on resistance-training induced stress responses. Therefore, the aim of this observational study was to investigate subjective symptoms and objective signs of immunological stress responses following resistance training in young athletes. Fourteen (7 females and 7 males) track and field athletes with a mean age of 16.4 years and without any symptoms of upper or lower respiratory tract infections participated in this study. Over a period of 7 days, subjective symptoms using the Acute Recovery and Stress Scale (ARSS) and objective signs of immunological responses using capillary blood markers were taken each morning and after the last training session. Differences between morning and evening sessions and associations between subjective and objective parameters were analyzed using generalized estimating equations (GEE). In post hoc analyses, daily change-scores of the ARSS dimensions were compared between participants and revealed specific changes in objective capillary blood samples. In the GEE models, recovery (ARSS) was characterized by a significant decrease while stress (ARSS) showed a significant increase between morning and evening-training sessions. A concomitant increase in white blood cell count (WBC), granulocytes (GRAN) and percentage shares of granulocytes (GRAN%) was found between morning and evening sessions. Of note, percentage shares of lymphocytes (LYM%) showed a significant decrease. Furthermore, using multivariate regression analyses, we identified that recovery was significantly associated with LYM%, while stress was significantly associated with WBC and GRAN%. Post hoc analyses revealed significantly larger increases in participants’ stress dimensions who showed increases in GRAN%. For recovery, significantly larger decreases were found in participants with decreases in LYM% during recovery. More specifically, daily change-scores of the recovery and stress dimensions of the ARSS were associated with specific changes in objective immunological markers (GRAN%, LYM%) between morning and evening-training sessions. Our results indicate that changes of subjective symptoms of recovery and stress dimensions using the ARSS were associated with specific changes in objectively measured immunological markers.

Probing the molecular regulation of lipopolysaccharide stress in piglet liver by comparative proteomics analysis.

Lipopolysaccharide (LPS) can induce inflammatory responses in piglets, causing immunological stress and tissue damage. However, chronic LPS infection may lead to LPS-induced immunological stress resistance. The molecular mechanisms underlying LPS stress have not been fully elucidated. Here, we conducted a global comparative proteomics analysis to investigate the molecular regulation of LPS stress using an immunological stress model of weaned piglets. A shotgun-based SWATH-MS workflow was used for global proteomes of the piglet livers after 15-day LPS treatment. Out of 3700 quantified proteins, 93 proteins showed differential changes under LPS stress. Bioinformatics analysis indicated that the differentially expressed proteins were mainly involved in inflammatory response, oxidation-redox processes and defense reactions, and were enriched in a phagosome pathway. Several key proteins associated with oxidative stress (SOD2), inflammation response (STEAP4 and S100 family) and the phagosome pathway were verified by activity and targeted-MS analyses. The observed responses appear to mitigate hepatic damage due to excessive oxidative stress, inflammation, and repression of the phagosome pathway. Our results reveal that an increased STEAP4 expression in piglets appears involved in cellular regulation by LPS stress and subsequent immunological stress resistance. This study sheds new light on the mechanism of prevention and relieving injury by LPS-induced immune responses.

Dietary L-theanine alleviated lipopolysaccharide-induced immunological stress in yellow-feathered broilers

L-theanine, a natural nonprotein amino acid with a high biological activity, is reported to exert anti-stress properties. An experiment with a 3 × 2 factorial arrangement was conducted to investigate the effects of dietary L-theanine on growth performance and immune function in lipopolysaccharide (LPS)-challenged broilers. A total of 432 one-day-old male yellow-feathered broilers were randomly assigned to 3 dietary treatments (control, antibiotic and L-theanine diets) with 2 subgroups of each (6 replicate cages; 12 birds/cage). Birds from each subgroup of the 3 dietary treatments were intra-abdominally injected with the same amount of LPS or saline at 24, 25, 26 d of age. Both dietary L-theanine and antibiotic improved (P < 0.05) the growth performance of birds before LPS injection (d 1 to 21). The effect of dietary L-theanine was better (P < 0.05) than that of antibiotic. Lipopolysaccharide decreased feed intake (FI) and body weight gain (BWG) from d 22 to 28 (P < 0.05), BWG and feed to gain ratio (F:G) from d 29 to 56 (P < 0.05), increased mortality in different growth periods (P < 0.05), elevated the levels of serum cortisol, α1-acid glycoprotein (α1-AGP), interleukin-6 (IL-6) on d 24 and 25 (P < 0.05), reduced immune organ indexes and contents of jejunal mucosal secretory immunoglobulin A (sIgA) on d 28 (P < 0.05). The decreased FI and BWG, as well as increased F:G and mortality in LPS-challenged birds, were alleviated by dietary L-theanine or antibiotic from d 29 to 56 and from d 1 to 56. Dietary L-theanine mitigated the elevated serum α1-AGP level on d 25, serum IL-6 concentration on d 24 and 26, and the decreased jejunal mucosal sIgA content on d 28 of the LPS-challenged birds. The results indicated that L-theanine had potential to alleviate LPS-induced immune stress in broilers.

Exosome markers associated with immune activation and oxidative stress in HIV patients on antiretroviral therapy

Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.

Fire service instructors' working practices: A UK survey

ABSTRACTAnalysis of Fire Service Instructors (FSI) working practices and health is needed to minimise health risks related to heat illness, cardiovascular events and immunological stress. Online surveys were distributed to UK FSI and Firefighters (FF). One hundred and thirty FSI (age: 43 ± 7yrs) and 232 FF (age: 41 ± 8yrs) responded. FSI experienced 2–10 live fires per week, with 45% of FSI reporting management does not set a limit on the number of exposures. Few FSI followed hydration guidelines, or cooling methods. New symptoms of ill health were reported by 41% of FSI and 21% of FF. FSI with ≥11 Breathing Apparatus exposures per month were 4.5 times (95% CI 1.33–15.09) more likely to experience new symptoms. A large proportion of FSI are experiencing new symptoms of illness after starting their career, and guidelines on exposure and hydration are not universally in place to reduce the risk of future health problems.

Mast cell corticotropin releasing factor receptor CRF2 regulates mast cell function in response to psychological and immunological stress

Abstract Psychological stress is a significant risk factor in a number of inflammatory and allergic diseases. We have previously demonstrated that CRF1 receptors expressed on mast cells (MCs) can potentiate psychological stress-induced MC degranulation intestinal permeability, and IgE-mediated anaphylaxis. In this study, we investigated the role of the CRF2 receptors in regulating MC activation in response to psychological and immunological stress. CRF2-deficient (CRF2−/−) bone marrow derived MCs exhibited enhanced IgE-and c48/80-mediated mast cell degranulation, determined by β-hex and histamine release. Heightened degranulation in CRF2−/− MCs were mediated by enhanced intracellular Ca2+ mobilization from endoplasmic reticulum stores. Similar results were obtained with human LAD2 mast cells treated with the CRF2 antagonist Astressin 2B. In vitro findings translated to in vivo studies as MC-deficient KitW-sh/W-sh mice systemically engrafted with CRF2−/− BMMCs exhibited a 3-fold increase in serum histamine levels and intestinal permeability following acute restraint stress or passive systemic anaphylaxis. Contrasting effects of CRF2 were observed with de novo synthesized mediator release as IL-4, IL-6, MCP-1 and prostaglandin D2 release were reduced (by ~40–50%) in CRF2−/− BMMCs following stimulation with IgE-antigen, LPS and IL-33. In summary, these data show that CRF2 signaling inhibits MC degranulation and associated pathophysiology induced by acute psychological stress and IgE-mediated anaphylaxis, while enhancing the release of de novo synthesized mediators. Therefore, targeting CRF2 may represent a novel therapeutic approach for preventing stress-related allergic and inflammatory disease flares.

Selenium Pretreatment Alleviated LPS-Induced Immunological Stress Via Upregulation of Several Selenoprotein Encoding Genes in Murine RAW264.7 Cells.

This study was conducted to profile selenoprotein encoding genes in mouse RAW264.7 cells upon lipopolysaccharide (LPS) challenge and integrate their roles into immunological regulation in response to selenium (Se) pretreatment. LPS was used to develop immunological stress in macrophages. Cells were pretreated with different levels of Se (0, 0.5, 1.0, 1.5, 2.0μmol Se/L) for 2h, followed by LPS (100ng/mL) stimulation for another 3h. The mRNA expression of 24 selenoprotein encoding genes and 9 inflammation-related genes were investigated. The results showed that LPS (100ng/mL) effectively induced immunological stress in RAW264.7 cells with induced inflammation cytokines, IL-6 and TNF-α, mRNA expression, and cellular secretion. LPS increased (P <0.05) mRNA profiles of 9 inflammation-related genes in cells, while short-time Se pretreatment modestly reversed (P < 0.05) the LPS-induced upregulation of 7 genes (COX-2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, and MCP-1) and further increased (P < 0.05) expression of IFN-β and TNF-α in stressed cells. Meanwhile, LPS decreased (P < 0.05) mRNA levels of 18 selenoprotein encoding genes and upregulated mRNA levels of TXNRD1 and TXNRD3 in cells. Se pretreatment recovered (P < 0.05) expression of 3 selenoprotein encoding genes (GPX1, SELENOH, and SELENOW) in a dose-dependent manner and increased (P < 0.05) expression of another 5 selenoprotein encoding genes (SELENOK, SELENOM, SELENOS, SELENOT, and TXNRD2) only at a high level (2.0μmol Se/L). Taken together, LPS-induced immunological stress in RAW264.7 cells accompanied with the global downregulation of selenoprotein encoding genes and Se pretreatment alleviated immunological stress via upregulation of a subset of selenoprotein encoding genes.