Short communication: Supply of methionine during late pregnancy enhances whole-blood innate immune response of Holstein calves partly through changes in mRNA abundance in polymorphonuclear leukocytes

The aims of this study were to investigate the effect of Saccharomyces cerevisiae var. boulardii CNCM I-1079 (SCB) or Lactobacillus acidophilus BT1386 (LA) on (1) innate immune response, (2) markers of acute-phase reaction, and (3) immune gene expression of rumen and ileum tissues of Holstein calves. Forty eight calves (∼5 d old) were randomly allocated to four treatments as follows: (1) control (CTRL) fed milk replacer followed by starter feed, (2) CTRL supplemented with SCB in milk and feed, (3) CTRL supplemented with LA in milk and feed, and (4) CTRL supplemented with antibiotics (ATB; chlortetracycline and neomycin in milk, and chlortetracycline in feed). Tumor necrosis factor α (TNF-α) decreased (P < 0.05) on day 66 (post-weaning) for the ATB-treated calves. There were no treatment effects on production of interferon γ (IFN-γ) and interleukin 6 (IL-6) proteins and on expression of TLR4, TLR6, TLR9, TLR10, CLDN3, MUC1, and MUC20 genes. Calves fed SCB or LA had a greater (P < 0.05) oxidative burst at weaning (day 53) compared with CTRL. Oxidative burst was also greater (P < 0.05) after weaning (day 59 and day 87) for SCB-fed calves. Calves fed SCB and ATB had higher (P < 0.05) phagocytosis activity during weaning (day 47) compared with CTRL. The concentration of serum amyloid A2 (SAA2) increased (P < 0.05) in SCB- and LA-fed calves (day 53), whereas the concentration of C-reactive protein (CRP) increased (P < 0.05) in SCB-fed calves during weaning as compared with CTRL. Our results suggest that SCB could improve innate immune response (oxidative burst and phagocytosis) and markers of acute-phase reaction (CRP and SAA2), especially during critical periods like weaning.

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52 Young Scholar Presentation: Maternal supply of methionine during late-pregnancy alters in utero and neonatal development, hepatic one-carbon metabolism,and innate immune response in Holstein calves

Journal of Animal Science ◽

10.1093/jas/skz122.049 ◽

2019 ◽

Vol 97 (Supplement_2) ◽

pp. 26-27

Author(s):

A S Alharti ◽

Juan Loor ◽

Fernanda Batistel ◽

Michael A Ballou ◽

Claudia Parys ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Carbon Metabolism ◽

Liver Tissue ◽

Average Daily Gain ◽

Plasma Concentrations ◽

Late Pregnancy ◽

Innate Immune ◽

Metabolism Enzymes ◽

Transsulfuration Pathway

Abstract Pregnancy and early life are critical periods of plasticity during which the fetus and neonate may be influenced by environmental factors such as nutrition. Objectives were to investigate if increasing methionine (Met) supply during late-pregnancy affects developmental, metabolic, and immune parameters of the calf at birth and during the neonatal period. Calves born to Holstein cows individually-fed a basal control (CON; 1.47 Mcal/kg dry matter [DM] and 15.3% crude protein) diet with no added Met or CON plus rumen-protected Met (MET; Mepron® at 0.09% of diet DM) during the last 28±2 d of pregnancy were used. Liver biopsies were harvested at 4, 14, 28, and 50 d of age and used for metabolomics via GS-MS and activity of hepatic 1-carbon metabolism enzymes. Blood for biomarker analyses and innate immune function assays was harvested at birth (before colostrum feeding), 7, 21, 42 and 50 d of age. Whole blood was challenged with enteropathogenic bacteria (E. coli 0118:H8), and phagocytosis and oxidative burst of neutrophils and monocytes quantified by flow cytometry. At birth, MET calves had greater (P≤0.05) body weight (BW, 44.1 vs. 42.1±0.70 kg), hip height (HH, 81.3 vs. 79.6±0.53 cm), and wither height (WH, 77.8 vs. 75.9±0.47 cm). Differences persisted through 9 wk of age, resulting in average responses of +3.1 kg BW, +1.9 cm HH, and+1.8 cm WH in MET compared with CON. Average daily gain during the 9 wk was (P<0.05) 0.72±0.02 kg/d in MET and 0.67±0.02 kg/d in CON calves. Despite similar rates of daily DMI, maternal supplementation with Met led to greater (P ≤ 0.05) overall hepatic concentrations of the 1-carbon metabolism intermediates adenosine, betaine, choline, glycine, and N,N-dimethylglycine in liver tissue. Among transsulfuration pathway metabolites, concentrations of cystathionine, cysteinesulfinic acid, hypotaurine, serine, and taurine were greater (P ≤ 0.05) in MET calves. There was a treatment × day effect for activity of betaine-homocysteine S-methyltransferase (BHMT), methionine synthase (MTR) and cystathionine-beta-synthase (CBS) in liver tissue. Activity of BHMT and CBS increased in MET calves between d 4 and 14, with a peak at 28 d. Despite a linear increase from d 4 to 28, activity of MTR in MET calves was lower on d 4 and 50. Plasma concentrations of haptoglobin and activity of myeloperoxidase in both maternal groups increased (P ≤ 0.05) markedly between 0 and 7 d of age followed by a decrease to baseline at d 21 with responses being lower in MET compared with CON calves. In vitro phagocytosis in stimulated neutrophils was greater overall (P ≤ 0.05) in MET calves. Overall, data indicate that increasing the maternal supply of Met during late-pregnancy benefits calf growth in part through alterations in hepatic metabolism and innate immune response.

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Whole blood profiling of leprosy type 1(reversal) reactions highlights prominence of innate immune response genes

BMC Infectious Diseases ◽

10.1186/s12879-018-3348-6 ◽

2018 ◽

Vol 18 (1) ◽

Cited By ~ 1

Author(s):

Jamile Leão Rêgo ◽

Nadja de Lima Santana ◽

Paulo Roberto Lima Machado ◽

Marcelo Ribeiro-Alves ◽

Thiago Gomes de Toledo-Pinto ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Whole Blood ◽

Innate Immune ◽

Immune Response Genes

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10.11606/d.10.2020.tde-12052020-090340 ◽

2020 ◽

Author(s):

Laila Miyuri Morita

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Innate Immune ◽

Holstein Calves

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Expression of selected genes isolated from whole blood, liver and obex in lambs with experimental classical scrapie and healthy controls, showing a systemic innate immune response at the clinical end-stage

BMC Veterinary Research ◽

10.1186/s12917-018-1607-9 ◽

2018 ◽

Vol 14 (1) ◽

Cited By ~ 2

Author(s):

Siv Meling ◽

Kerstin Skovgaard ◽

Kjetil Bårdsen ◽

Peter Mikael Helweg Heegaard ◽

Martha J. Ulvund

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Whole Blood ◽

Classical Scrapie ◽

Innate Immune ◽

Healthy Controls ◽

End Stage

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Bovine innate immune phenotyping via a standardized whole blood stimulation assay

Scientific Reports ◽

10.1038/s41598-021-96493-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Cian Reid ◽

Charlotte Beynon ◽

Emer Kennedy ◽

Cliona O’Farrelly ◽

Kieran G. Meade

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

High Throughput ◽

Whole Blood ◽

Time Window ◽

Innate Immune ◽

Cell Manipulation ◽

High Throughput Analysis ◽

Immune Phenotyping ◽

Whole Blood Stimulation

AbstractCattle vary in their susceptibility to infection and immunopathology, but our ability to measure and longitudinally profile immune response variation is limited by the lack of standardized immune phenotyping assays for high-throughput analysis. Here we report longitudinal innate immune response profiles in cattle using a low-blood volume, whole blood stimulation system—the ImmunoChek (IChek) assay. By minimizing cell manipulation, our standardized system minimizes the potential for artefactual results and enables repeatable temporal comparative analysis in cattle. IChek successfully captured biological variation in innate cytokine (IL-1β and IL-6) and chemokine (IL-8) responses to 24-hr stimulation with either Gram-negative (LPS), Gram-positive (PamCSK4) bacterial or viral (R848) pathogen-associated molecular patterns (PAMPs) across a 4-month time window. Significant and repeatable patterns of inter-individual variation in cytokine and chemokine responses, as well as consistent high innate immune responder individuals were identified at both baseline and induced levels. Correlation coefficients between immune response read-outs (IL-1β, IL-6 and IL-8) varied according to PAMP. Strong significant positive correlations were observed between circulating monocytes and IL-6 levels for null and induced responses (0.49–0.61) and between neutrophils and cytokine responses to R848 (0.38–0.47). The standardized assay facilitates high-throughput bovine innate immune response profiling to identify phenotypes associated with disease susceptibility and responses to vaccination.

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Coagulation Activation By Heme: Evidence from Global Hemostasis Assays

Blood ◽

10.1182/blood.v124.21.455.455 ◽

2014 ◽

Vol 124 (21) ◽

pp. 455-455

Author(s):

Gleice Regina Souza ◽

Maiara M L Fiusa ◽

Carolina Lanaro ◽

Marina Pereira Colella ◽

Silmara A L Montalvao ◽

...

Keyword(s):

Immune Response ◽

Innate Immune Response ◽

Whole Blood ◽

Conflicts Of Interest ◽

Plasma Concentrations ◽

Maximum Velocity ◽

Innate Immune ◽

Acute Chest Syndrome ◽

Coagulation Activation

Abstract Introduction: It has been known for more than 50 years that patients with sickle cell disease (SCD) present higher plasma concentrations of heme. More recently, it was shown that heme is capable to activate innate immune response, and to trigger a toll-like receptor-dependent response that involves the expression of several pro-inflammatory genes. Accordingly, the role of heme as critical inflammatory mediator in SCD has been confirmed in different experimental models, suggesting that heme can be a trigger for microvascular occlusion and acute chest syndrome (ACS). The association between innate immune response and coagulation activation dates back to 450 million years in evolution, so that activation of the former is frequently accompanied by activation of the latter. Micro and macrovascular thrombosis are a hallmark of SCD, and the role of heme in the pathogenesis of these events has been recently suggested by demonstrations of heme-induced expression of tissue factor (TF) by endothelial cells and monocytes. However, the functional relevance of heme-induced TF expression on clinically-relevant coagulation markers has not been demonstrated. Methods: herein we evaluated heme-induced TF expression in peripheral blood mononuclear cells (PBMC), and used two different global assays of hemostasis, namely thromboelastometry (TEM) and Thrombin Generation Test (TGT) to evaluate the effect of heme on coagulation activation. Blood from healthy volunteers was drawn from an antecubital vein with minimal stasis in 0.106 sodium citrate tubes (1:10) or heparin. TEM was performed in whole-blood samples (n=10) incubated with 30 µM heme (Sigma-Aldrich) for four hours at 37oC, in a ROTEM equipment (Pentapharm). Coagulation was activated with the addition of CaCl2. Samples from same individuals incubated with vehicle were assayed concomitantly as controls (n=10). TGT was performed in double centrifuged plasma samples, separated from whole blood stimulated with heme or vehicle under the same conditions (n=16). TGT was performed using a Fluoroskan Ascent Flourimeter (Thermolab). Coagulation was activated with TF (5pM) and phospholipids (PPP reagent, Thrombinoscope). Expression of TF was evaluated by qRT-PCR. Heparin-anticoagulated blood was incubated with 30 µM heme (n=6) or vehicle (n=6) for 24 hours. PBMC and neutrophils were then separated by density gradient centrifugation (Ficoll). Non-parametric statistics were used in all analysis. Results: incubation of whole blood with heme 30 µM resulted in a potent induction of TF expression in PBMC compared to vehicle (AU)(0.03±0.06 vs 1.18±0.60; P=0.03). No TF expression could be detected in neutrophils. Heme-induced coagulation activation could be demonstrated by TEM. Heme significantly decreased the coagulation time (sec) (562.1±88.2 to 387±84.3; P=0.002) and the MaxV-t (time to maximum velocity) (651.4±119.2 to 451.1±87.4; P=0.002), which are two indicators of shift towards a hypercoagulable profile. A trend towards a lower clot formation time was also observed (P=0.07). No difference could be observed in the area under the TEM curve. A hypercoagulable profile was also observed in TGT in samples incubated with heme. Statistically significant changes compatible with a shift towards coagulation activation were observed in parameters such as peak thrombin (increased), time to peak thrombin (decreased), velocity index (increased), lagtime (decreased) and StarTail (decreased) (all P<0.05). No statistically significant change could be observed in the endogenous thrombin potential parameter (p=0.10). Discussion and conclusions: TEM and TGT are global hemostasis assays, widely used for evaluation of hypo- and hypercoagulable states. Both methods have been used in patients with SCD, who present hypercoagulable profiles similar to those obtained in our study, and characterized by faster onset and offset of coagulation activation. We demonstrate for the first time that heme, in concentrations similar to those observed in patients with SCD and other hemolytic disorders, is capable to not only stimulate the expression of TF by PBMC, but also to shift the coagulation balance towards a hypercoagulable state, similar to that observed in patients with SCD. These results provide additional support to the hypothesis that heme is a key mediator micro- and macrovascular thrombosis in SCD and possibly, in other hemolytic disorders. Disclosures No relevant conflicts of interest to declare.

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Gene expression profiling of Gram-negative bacteria-induced inflammation in human whole blood: The role of complement and CD14-mediated innate immune response

Genomics Data ◽

10.1016/j.gdata.2015.05.019 ◽

2015 ◽

Vol 5 ◽

pp. 176-183 ◽

Cited By ~ 2

Author(s):

Corinna Lau ◽

Ole Kristoffer Olstad ◽

Marit Holden ◽

Ståle Nygård ◽

Hilde Fure ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Innate Immune Response ◽

Whole Blood ◽

Expression Profiling ◽

Innate Immune ◽

Gram Negative Bacteria ◽

Gram Negative ◽

Human Whole Blood

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Oral Immune Activation by Disgust and Disease-Related Pictures

Journal of Psychophysiology ◽

10.1027/0269-8803/a000143 ◽

2015 ◽

Vol 29 (3) ◽

pp. 119-129 ◽

Cited By ~ 4

Author(s):

Richard J. Stevenson ◽

Deborah Hodgson ◽

Megan J. Oaten ◽

Luba Sominsky ◽

Mehmet Mahmut ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Innate Immune Response ◽

Negative Control ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Markers ◽

Before And After ◽

Secondary Analyses ◽

Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

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