scholarly journals Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0252175
Author(s):  
Katie L. Edwards ◽  
Erin M. Latimer ◽  
Jessica Siegal-Willott ◽  
Wendy Kiso ◽  
Luis R. Padilla ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Phase Proteins ◽  
Interleukin 2 ◽  
Underlying Disease ◽  
Hemorrhagic Disease ◽  
African Elephants ◽  
Necrosis Factor Alpha ◽  
Amyloid A ◽  
Immune Biomarkers ◽  
The Impact

Hemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. However, the overall low concentrations detected using previously validated assays do not support the presence of a ‘cytokine storm’ and suggest more work is needed to understand if sub-optimal immune responses could be involved in disease progression. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.

scholarly journals Patterns of serum immune biomarkers during elephant endotheliotropic herpesvirus viremia in Asian and African elephants

2021 ◽  
Author(s):  
Katie L Edwards ◽  
Erin Latimer ◽  
Jessica Siegal-Willott ◽  
Wendy Kiso ◽  
Luis Padilla ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Phase Proteins ◽  
Interleukin 2 ◽  
Hemorrhagic Disease ◽  
African Elephants ◽  
Necrosis Factor Alpha ◽  
Assay Sensitivity ◽  
Amyloid A ◽  
Immune Biomarkers ◽  
The Impact

Hemorrhagic disease (HD) caused by a group of elephant endotheliotropic herpesviruses (EEHV) is one of the leading causes of death for young elephants in human care. These viruses are widespread and typically persist latently in adult elephants with no negative effects; however, in juvenile Asian and more recently young African elephants, the onset of disease can be rapid and the mortality rate high. Measuring biomarkers associated with the immune response could be beneficial to understanding underlying disease processes, as well as the management of infection and HD. The goal of this study was to measure acute phase proteins and cytokines in serum collected from elephants infected with EEHV (13 Asian and 1 African) and compare concentrations according to presence, severity and outcome of disease. Serum amyloid A (SAA) and haptoglobin (HP) were higher in elephants with EEHV viremia than those without; concentrations increased with increasing viral load, and were higher in fatal cases compared to those that survived. In Asian elephants, SAA was also higher during EEHV1 viremia compared to EEHV5. Cytokine concentrations were typically low, and no statistical differences existed between groups, perhaps due to insufficient assay sensitivity in this age group. However, in individuals with detectable levels, longitudinal profiles indicated changes in tumor necrosis factor alpha (TNF-α) and interleukin-2 (IL-2) that may reflect an immune response to EEHV infection. These results highlight the potential benefit of measuring circulating biomarker concentrations, such as APPs and cytokines, to improve our understanding of EEHV viremia and HD, assist with monitoring the progression of disease and determining the impact of interventions.

scholarly journals Serum Health Biomarkers in African and Asian Elephants: Value Ranges and Clinical Values Indicative of the Immune Response

Animals ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1756
Author(s):  
Katie L. Edwards ◽  
Michele A. Miller ◽  
Jessica Siegal-Willott ◽  
Janine L. Brown
Keyword(s):  
Serum Amyloid A ◽  
Acute Phase Proteins ◽  
Serum Amyloid ◽  
Clinical Samples ◽  
Necrosis Factor Alpha ◽  
Amyloid A ◽  
Paired Samples ◽  
Immune Biomarkers ◽  
Tnf Α ◽  
Species Specific

Serum biomarkers indicative of inflammation and disease can provide useful information regarding host immune processes, responses to treatment and prognosis. The aims of this study were to assess the use of commercially available anti-equine reagents for the quantification of cytokines (tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins (IL) 2, 6, and 10) in African (Loxodonta africana, n = 125) and Asian (Elephas maximus, n = 104) elephants, and alongside previously validated anti-human reagents for acute-phase proteins (serum amyloid A and haptoglobin), calculate species-specific biomarker value ranges. In addition, we used opportunistically collected samples to investigate the concentrations of each biomarker during identified clinical cases of illness or injury, as a first step to understanding what biomarkers may be useful to managing elephant health. Immune biomarkers were each elevated above the calculated species-specific value ranges in at least one clinical case, but due to variability in both clinical and non-clinical samples, only serum amyloid A was significantly higher in clinical compared to non-clinical paired samples, with tendencies for higher TNF-α and IL-10. We also detected increased secretion of serum amyloid A and all five cytokines following routine vaccination of a single Asian elephant, indicating that these biomarkers can be beneficial for studying normal immune processes as well as pathology. This study indicates that assays developed with commercial reagents can be used to quantify health biomarkers in wildlife species and identifies several that warrant further investigation to elucidate immune responses to various pathologies.

scholarly journals Neutrophils Are Essential for Rapid Clearance of Enterococcus faecium in Mice

2008 ◽  
Vol 77 (1) ◽  
pp. 485-491 ◽  
Author(s):  
Masja Leendertse ◽  
Rob J. L. Willems ◽  
Ida A. J. Giebelen ◽  
Joris J. T. H. Roelofs ◽  
Marc J. M. Bonten ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Enterococcus Faecium ◽  
Acute Phase Proteins ◽  
Progressive Increase ◽  
Necrosis Factor Alpha ◽  
Amyloid A ◽  
Neutropenic Patients ◽  
Rapid Clearance ◽  
Factor Alpha

ABSTRACT A progressive increase in infections with multiresistant Enterococcus faecium has been reported, especially in cancer patients and neutropenic patients. Despite its increasing importance as a nosocomial pathogen, knowledge of the pathogenesis of E. faecium infections is highly limited. In this study, we investigated the role of neutrophils during peritonitis with subsequent bacteremia caused by E. faecium. Therefore, we depleted neutrophils by intraperitoneal injections of monoclonal antibody RB6-8C5. Mice were followed for 5 days, and the enterococcal outgrowth and inflammatory response were compared between neutropenic mice and immunoglobulin G-injected control mice. Neutropenic mice demonstrated a severe delay in enterococcal clearance from all cultured organs (peritoneal fluid, blood, and lung and liver tissue). In particular, neutropenic mice remained bacteremic for up to 3 days, whereas all nonneutropenic mice had cleared the bacteria from circulation by 2 days. Furthermore, neutropenic mice displayed elevated peritoneal cytokine and chemokine levels 1 day after the infection and attracted fewer macrophages into the peritoneal cavity. In the circulation, a prolonged elevation of tumor necrosis factor alpha, interleukin-6, and the acute-phase proteins serum amyloid A and complement 3 were measured in neutropenic mice. In conclusion, attraction of neutrophils to the primary site of E. faecium infection is important for a rapid clearance of this bacterium, thereby attenuating a systemic inflammatory response.

scholarly journals Mycobacterium tuberculosis Immune Response in Patients With Immune-Mediated Inflammatory Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Elisa Petruccioli ◽  
Linda Petrone ◽  
Teresa Chiacchio ◽  
Chiara Farroni ◽  
Gilda Cuzzi ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Cd4 T Cells ◽  
Interleukin 2 ◽  
Developed Countries ◽  
Preventive Therapy ◽  
T Cell Response ◽  
Specific Response ◽  
Immune Biomarkers ◽  
Immune Mediated

Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis (RA), have an intrinsic higher probability to develop active-tuberculosis (TB) compared to the general population. The risk ranges from 2.0 to 8.9 in RA patients not receiving therapies. According to the WHO, the RA prevalence varies between 0.3% and 1% and is more common in women and in developed countries. Therefore, the identification and treatment of TB infection (TBI) in this fragile population is important to propose the TB preventive therapy. We aimed to study the M. tuberculosis (Mtb) specific T-cell response to find immune biomarkers of Mtb burden or Mtb clearance in patients with different TB status and different risk to develop active-TB disease. We enrolled TBI subjects as example of Mtb-containment, the active-TB as example of a replicating Mtb status, and the TBI-IMID as fragile population. To study the Mtb-specific response in a condition of possible Mtb sterilization, we longitudinally enrolled TBI subjects and active-TB patients before and after TB therapy. Peripheral blood mononuclear cells were stimulated overnight with Mtb peptides contained in TB1- and TB2-tubes of the Quantiferon-Plus kit. Then, we characterized by cytometry the Mtb-specific CD4 and CD8 T cells. In TBI-IMID, the TB therapy did not affect the ability of CD4 T cells to produce interferon-γ, tumor necrosis factor-α, and interleukin-2, their functional status, and their phenotype. The TB therapy determined a contraction of the triple functional CD4 T cells of the TBI subjects and active-TB patients. The CD45RA- CD27+ T cells stood out as a main subset of the Mtb-specific response in all groups. Before the TB-preventive therapy, the TBI subjects had higher proportion of Mtb-specific CD45RA-CD27+CD4+ T cells and the active-TB subjects had higher proportion of Mtb-specific CD45RA-CD27-CD4+ T cells compared to other groups. The TBI-IMID patients showed a phenotype similar to TBI, suggesting that the type of IMID and the IMID therapy did not affect the activation status of Mtb-specific CD4 T cells. Future studies on a larger and better-stratified TBI-IMID population will help to understand the change of the Mtb-specific immune response over time and to identify possible immune biomarkers of Mtb-containment or active replication.

Intramammary infusion of a live culture for treatment of bovine mastitis: effect of live lactococci on the mammary immune response

2008 ◽  
Vol 75 (3) ◽  
pp. 374-384 ◽  
Author(s):  
Fiona Crispie ◽  
Mercedes Alonso-Gómez ◽  
Collette O'Loughlin ◽  
Katja Klostermann ◽  
James Flynn ◽  
...  
Keyword(s):  
Immune Response ◽  
Lactococcus Lactis ◽  
Acute Phase Proteins ◽  
Bovine Mastitis ◽  
Field Trials ◽  
Initial Field ◽  
Amyloid A ◽  
Probiotic Treatment ◽  
Post Infusion ◽  
Live Culture

In the accompanying article, we demonstrated that a live culture ofLactococcus lactiscompares favourably with antibiotics for treatment of bovine mastitis in two initial field trials. In an effort to explain the mechanism involved, this study investigated the effect of culture administration on the local immune response. In this respect we initially observed that infusion of the live cultureLactococcus lactisstimulated substantial recruitment of polymorphonucleocytes (PMN) and lymphocytes to the udder. For instance, in one assay, quarters infused with the probiotic experienced a dramatic increase (~20 000-fold) in neutrophils over the first 48-h period from an average value of 83·6 cells/ml pre-treatment to 1·78×106 cells/ml 48 h post-infusion. Levels of the acute phase proteins haptaglobin and milk amyloid A were also elevated significantly in comparison with controls following infusion of the culture. The results of flow cytometric assays also demonstrated that while infusion of a live lactococcal culture led to an enhanced recruitment of PMN to the udder (from 1·85×104 cells/ml pre-infusion to 1·45×106 cells/ml 24 h post-infusion) cell-free supernatant from the same culture was not able to do so, indicating that liveLc. lactiscan specifically trigger the mammary immune response to elicit PMN accumulation. These results suggest that the mechanism responsible for this probiotic treatment of mastitis is associated with stimulation of the host intramammary immune system.

scholarly journals Impact of radioiodine treatment on acute phase proteins in hyperthyroid cats

2021 ◽  
pp. 1098612X2110249
Author(s):  
Katharina Glück ◽  
Sabrina Mohrs ◽  
Katarina Hazuchova ◽  
Natali Bauer ◽  
Reto Neiger
Keyword(s):  
Acute Phase ◽  
Acute Phase Proteins ◽  
Fold Increase ◽  
Neoplastic Disease ◽  
Phase Reaction ◽  
Radioiodine Treatment ◽  
Serum Samples ◽  
Amyloid A ◽  
The Impact

Objectives The aim of this study was to investigate the impact of radioiodine treatment (RIT) on the acute phase proteins (APPs) serum amyloid A (SAA), alpha-1-acid glycoprotein (AGP) and haptoglobin (Hp) in hyperthyroid cats. Methods Between June 2013 and November 2014, 33 hyperthyroid cats without clinical or laboratory signs of inflammatory or neoplastic disease and a body weight >2.5 kg were enrolled. Immediately before, and 12, 36, 72 h and 6 days after RIT, serum samples were obtained for determination of APP concentrations. Results Both SAA and AGP concentrations changed significantly after RIT. The concentration of AGP increased gradually after treatment with a maximum concentration at the end of the study period (median baseline 398 μg/ml; median 6 days post-RIT 562 μg/ml [ P = 0.001]). A relevant >two-fold increase in AGP was seen in 8/33 (24%) cats. SAA concentration increased significantly within 12 h (baseline 9.2 μg/ml; 12 h post-RIT 22.5 μg/ml [ P = 0.012]). In 7/33 (21%) cats, a clinically relevant >10-fold increase in SAA was observed. Hp concentration showed no significant change ( P = 0.12). Conclusions and relevance RIT induced a mild, mainly not clinically relevant acute phase reaction (APR). AGP and SAA were useful APPs to determine RIT-induced APR.

scholarly journals The Effect of Feed Supplementation with EM Bokashi® Multimicrobial Probiotic Preparation on Selected Parameters of Sow Colostrum and Milk as Indicators of the Specific and Nonspecific Immune Response

2021 ◽  
Author(s):  
Łukasz Jarosz ◽  
Artur Ciszewski ◽  
Agnieszka Marek ◽  
Zbigniew Grądzki ◽  
Beata Kaczmarek ◽  
...  
Keyword(s):  
Immune Response ◽  
Acute Phase Proteins ◽  
Large White ◽  
Humoral Immune ◽  
Amyloid A ◽  
Group A ◽  
Pig Farm ◽  
Probiotic Microbes ◽  
Nonspecific Immune Response

AbstractThe aim of the study was to determine the effect of EM Bokashi® on selected parameters of the specific and nonspecific immune response of sows by in colostrum and milk samples. The percentage of cells with expression of CD19+, CD5+CD19+, CD21+, SWC3a (macrophage/monocyte), and CD11b+ molecules on the monocytes and granulocytes as well as the concentrations of lysozyme and acute phase proteins — serum amyloid-A (SAA) and haptoglobin (Hp) were evaluated. The study was carried out on a commercial pig farm, including 150 sows (Polish Large White × Polish Landrace) at the age of 2–4 years. Sixty female sows were divided into two groups: I — control and II — experimental. For the experimental group, a probiotic in the form of the preparation EM Bokashi® in the amount of 10 kg/tonne of feed was added to the basal feed from mating to weaning. The material for the study consisted of colostrum and milk. The samples were collected from all sows at 0, 24, 48, 72, 96, 120, 144, and 168 h after parturition. The study showed that exposure of the pregnant sow to the probiotic microbes contained in EM Bokashi® significantly affects the immunological quality of the colostrum and milk and caused an increase in the percentage of the subpopulations of B cells with CD19+, CD21+, and CD5+CD19+ expression in the colostrum and milk, which demonstrates an increase in the protective potential of colostrum and indicates stimulation of humoral immune mechanisms that protect the sow and the piglets against infections.

scholarly journals Investigation of acute-phase proteins and cytokines response in goats with contagious caprine pleuropneumonia with special reference to their diagnostic accuracy

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e10394
Author(s):  
Wael El-Deeb ◽  
Mahmoud Fayez ◽  
Ibrahim Elsohaby ◽  
Mohamed Salem ◽  
Abdulrhman Alhaider ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Acute Phase ◽  
Acute Phase Proteins ◽  
Latex Agglutination ◽  
Moderate Degree ◽  
Serum Samples ◽  
Necrosis Factor Alpha ◽  
Reactive Protein ◽  
Amyloid A ◽  
Contagious Caprine Pleuropneumonia

Acute-phase proteins (APPs) have always had valued diagnostic potentialities in response to infection. This study aimed to evaluate the diagnostic accuracy of selected APPs and proinflammatory cytokines (PIC) in goats with contagious caprine pleuropneumonia (CCPP) under field conditions. Moreover, to highlight the role of tested biomarkers in CCPP pathogenesis. Fifty-eight goats (38 confirmed cases with CCPP and 20 healthy controls) were involved in this investigation. C-reactive protein (CRP), procalcitonin (PCT), haptoglobin (HP), fibrinogen (Fb), serum amyloid A (SAA), selected PIC (IL1-α, IL1-β, IL-6, interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α)) levels were investigated in serum samples from all goats under investigation. Latex agglutination test was used for diagnosis of goats with CCPP. For microbiological investigations, nasopharyngeal swabs (from all goats), lung tissues and pleural fluids (from only necropsied goats) were collected. This study revealed that all tested parameters have a high to moderate degree of diagnostic performance for CCPP. Magnitudes of increase in levels of APPs (CRP, HP and SAA) were stronger than PIC, IFN-γ, Fb and PCT. All tested parameters showed high diagnostic accuracy (AUROC >90%), except HP (AUROC = 87.3%) and IFN-γ (AUROC = 78.8%) showed moderate accuracy in differentiation of goats with and without CCPP infection. For detecting goats with and without CCPP infection, HP had the lowest sensitivity (Se = 81.6%) and Fb had the lowest specificity (Sp = 85.0%) among the APPs parameters tested. However, PCT showed the highest Se (100%) and Sp (95.0%) to detect goats with and without CCPP infection among tested parameters. Conclusively, this study endorses the significance of selected APPs and PIC as additional screening diagnostic parameters for naturally occurring CCPP in goats. However, it does not replace traditional methods for diagnosis of CCPP in goats. Furthermore, APPs and PIC have an important role in disease pathogenesis in goats.

scholarly journals 16 Sulfur amino acid utilization during immune system stimulation in growing pigs

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 15-16
Author(s):  
Anoosh Rakhshandeh
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Amino Acid ◽  
Acute Phase Proteins ◽  
Growing Pigs ◽  
Synthesis Rate ◽  
Ileal Digestibility ◽  
Maintenance Requirement ◽  
Elevated Rate ◽  
The Impact

Abstract Immune system stimulation (ISS) modifies protein and amino acid (AA) metabolism in animals and humans. During ISS, AA are redirected away from growth and reproduction towards mounting an immune response. This redirection can impact AA requirements both qualitatively (i.e., the AA ratio) and quantitatively. Special attention has been given to sulfur-containing amino acid (SAA; Met + Cys) metabolism during ISS, due to their roles as precursors for the synthesis of proteins and metabolites that are involved in the immune response. A series of studies were conducted to investigate the impact of ISS on various aspects of SAA utilization, including ileal digestibility, plasma kinetics, the glutathione (GSH) synthesis rate, the irreversible loss of Cys, and dietary total SAA requirements. In all of the studies, pigs were feed restricted (≥ 2 times the maintenance requirement for ME) to eliminate the confounding effect of ISS on feed intake. Results indicated that ISS alters SAA metabolism and increases SAA requirements per unit of protein deposition. The latter occurs due to increased maintenance requirements for SAA during ISS. The results also showed that the enhanced maintenance requirement for SAA occurs mainly as a result of increased SAA utilization, mainly Cys, for the synthesis of immune system metabolites, such as GSH and acute-phase proteins, as well as the increased catabolism of Cys to taurine. In addition, we found that ISS increases the dietary Met-to-total SAA ratio in pigs, suggesting an enhanced preferential demand for dietary Met during ISS, perhaps to support an elevated rate of transsulfuration. Collectively, our findings point toward a need for developing an optimal dietary AA profile for diseased pigs.

scholarly journals The Tumor Necrosis Factor Alpha and Interleukin 6 Auto-paracrine Signaling Loop Controls Mycobacterium avium Infection via Induction of IRF1/IRG1 in Human Primary Macrophages

mBio ◽  
2021 ◽  
Author(s):  
Alexandre Gidon ◽  
Claire Louet ◽  
Lisa Marie Røst ◽  
Per Bruheim ◽  
Trude Helen Flo
Keyword(s):  
Mycobacterium Avium ◽  
Underlying Disease ◽  
Paracrine Signaling ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Avium Infection ◽  
Factor Alpha ◽  
The Impact ◽  
Mycobacterium Avium Infection ◽  
Necrosis Factor

The prevalence of lung diseases caused by nontuberculous mycobacteria, such as Mycobacterium avium , is increasing in countries where tuberculosis is not endemic, most likely because of an aging population that is immunocompromised from underlying disease or immunosuppressive therapy. Our study contributes to the understanding of mycobacterial survival and killing in human macrophages and, more broadly, to the impact of immunometabolism during infection.

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