Uncomplicated Plasmodium vivax malaria: mapping the proteome from circulating platelets

Background Thrombocytopenia is frequent in Plasmodium vivax malaria but the role of platelets in pathogenesis is unknown. Our study explores the platelet (PLT) proteome from uncomplicated P. vivax patients, to fingerprint molecular pathways related to platelet function. Plasma levels of Platelet factor 4 (PF4/CXCL4) and Von Willebrand factor (VWf), as well as in vitro PLTs—P. vivax infected erythrocytes (Pv-IEs) interactions were also evaluated to explore the PLT response and effect on parasite development. Methods A cohort of 48 patients and 25 healthy controls were enrolled. PLTs were purified from 5 patients and 5 healthy controls for Liquid Chromatography–Mass spectrometry (LC–MS/MS) analysis. Plasma levels of PF4/CXCL4 and VWf were measured in all participants. Additionally, P. vivax isolates (n = 10) were co-cultured with PLTs to measure PLT activation by PF4/CXCL4 and Pv-IE schizonts formation by light microscopy. Results The proteome from uncomplicated P. vivax patients showed 26 out of 215 proteins significantly decreased. PF4/CXCL4 was significantly decreased followed by other proteins involved in platelet activation, cytoskeletal remodeling, and endothelial adhesion, including glycoprotein V that was significantly decreased in thrombocytopenic patients. In contrast, acute phase proteins, including SERPINs and Amyloid Serum A1 were increased. High levels of VWf in plasma from patients suggested endothelial activation while PF4/CXCL4 plasma levels were similar between patients and controls. Interestingly, high levels of PF4/CXCL4 were released from PLTs—Pv-IEs co-cultures while Pv-IEs schizont formation was inhibited. Conclusions The PLT proteome analyzed in this study suggests that PLTs actively respond to P. vivax infection. Altogether, our findings suggest important roles of PF4/CXCL4 during uncomplicated P. vivax infection through a possible intracellular localization. Our study shows that platelets are active responders to P. vivax infection, inhibiting intraerythrocytic parasite development. Future studies are needed to further investigate the molecular pathways of interaction between platelet proteins found in this study and host response, which could affect parasite control as well as disease progression.

Acute phase proteins in veterinary medicine: A review

The acute phase proteins (APPs) are a group of blood proteins that contribute to restoring homeostasis and limiting microbial growth in an antibody-independent manner in animals which are exposed to different pathological conditions like infection, inflammation, surgical trauma and stress. In the last two decades, many advances have been made in monitoring APPs in both farm and companion animals for clinical and experimental purposes. Also, the mechanism of the APPs response is receiving attention in veterinary science in connection with the innate immune systems of animals. This review describes the many of new results of research and role APPs in farm animal, with special reference to their functions, types, induction and regulatory expression, some of biological functions, and their current and future applications to veterinary diagnosis and animal production.

Changes in Acute-Phase Proteins in Plasma during the Periparturient Period of Dairy Goats

The present study was conducted regarding four acute-phase proteins (APPs) including C-reactive protein (CRP), ceruloplasmin (CP), serum amyloid A (SAA), and haptoglobin (HP) in dairy goats during the periparturient period. The aim of this study was to detect the changes in APPs in plasma during the periparturient period of healthy dairy goats. Guanzhong dairy goats with no other symptoms (n = 15) were selected on the basis of their blood calcium (Ca) and β-hydroxybutyrate (BHBA) concentration. The plasma was collected once a week for ±3 weeks delivery. The concentrations of the four APPs mentioned above were determined using goat-specific ELISA kits. The results showed the CRP level in plasma decreased from 3 weeks to 1 week antepartum and increased later until 1 week postpartum and then decreased to a similar level with antepartum between 1 and 3 weeks postpartum. The content of CP showed a decline in 3 weeks before parturition and an upward trend between 1 week antepartum and 3 weeks postpartum. The SAA concentration decreased from 3 weeks antepartum to 2 weeks postpartum and rebounded later. The level of HP decreased during 3 weeks before parturition and increased until 1 week postpartum, then reached a stable value. Clear variation range and rules of APPs contribute to perinatal health monitoring of dairy goats.

Low-Grade Systemic Inflammation Interferes with Anabolic and Catabolic Characteristics of the Aged Human Skeletal Muscle

Aging is associated with the development of chronic low-grade systemic inflammation (LGSI) characterized by increased circulating levels of proinflammatory cytokines and acute phase proteins such as C-reactive protein (CRP). Collective evidence suggests that elevated levels of inflammatory mediators such as CRP, interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) are correlated with deteriorated skeletal muscle mass and function, though the molecular footprint of this observation in the aged human skeletal muscle remains obscure. Based on animal models showing impaired protein synthesis and enhanced degradation in response to LGSI, we compared here the response of proteolysis- and protein synthesis-related signaling proteins as well as the satellite cell and amino acid transporter protein content between healthy older adults with increased versus physiological blood hs-CRP levels in the fasted (basal) state and after an anabolic stimulus comprised of acute resistance exercise (RE) and protein feeding. Our main findings indicate that older adults with increased hs-CRP levels demonstrate (i) increased proteasome activity, accompanied by increased protein carbonylation and IKKα/β phosphorylation; (ii) reduced Pax7+ satellite cells; (iii) increased insulin resistance, at the basal state; and (iv) impaired S6 ribosomal protein phosphorylation accompanied by hyperinsulinemia following an acute RE bout combined with protein ingestion. Collectively, these data provide support to the concept that age-related chronic LGSI may upregulate proteasome activity via induction of the NF-κB signaling and protein oxidation and impair the insulin-dependent anabolic potential of human skeletal muscle.

Age-Related Changes in Acute Phase Reaction, Cortisol, and Haematological Parameters in Ewes in the Periparturient Period

A well-functioning immune system is the basis for protection against infectious and metabolic diseases, and a smooth return to homeostasis. The periparturient period is considered critical because major changes in the endocrine, behavioural, digestive, and immune systems dysregulate immune function, leading to immunosuppression. With age, the immune system could become dysregulated. The purpose of the present investigation was to compare changes in plasma concentrations of acute phase proteins, cortisol, and haematological parameters in the peripheral blood of two age-related groups of healthy ewes to get a better understanding of changes around lambing. Two groups of ewes were enrolled in the study: 3-year-old (young; n = 9) and 7-year-old ewes (old; n = 9). All females were synchronised and inseminated. In blood plasma, serum amyloid A (SAA) and cortisol concentrations were measured using ELISA tests, a spectrophotometric method to determine haptoglobin (Hp), and a thrombin clottable estimation to determine the fibrinogen (Fb) concentration. The blood parameters were examined using an automated haematological analyser. In clinically healthy ewes, no significant effect of age was observed in SAA, Hp, Fb and cortisol concentration in most of analysed terms. SAA, Hp, Fb, and cortisol fluctuations typical for the periparturient period were observed. There were no age-associated differences in red or white blood cell parameters.

Fetal Immunomodulatory Environment Following Cartilage Injury—The Key to CARTILAGE Regeneration?

Fetal cartilage fully regenerates following injury, while in adult mammals cartilage injury leads to osteoarthritis (OA). Thus, in this study, we compared the in vivo injury response of fetal and adult ovine articular cartilage histologically and proteomically to identify key factors of fetal regeneration. In addition, we compared the secretome of fetal ovine mesenchymal stem cells (MSCs) in vitro with injured fetal cartilage to identify potential MSC-derived therapeutic factors. Cartilage injury caused massive cellular changes in the synovial membrane, with macrophages dominating the fetal, and neutrophils the adult, synovial cellular infiltrate. Correspondingly, proteomics revealed differential regulation of pro- and anti-inflammatory mediators and growth-factors between adult and fetal joints. Neutrophil-related proteins and acute phase proteins were the two major upregulated protein groups in adult compared to fetal cartilage following injury. In contrast, several immunomodulating proteins and growth factors were expressed significantly higher in the fetus than the adult. Comparison of the in vitro MSCs proteome with the in vivo fetal regenerative signature revealed shared upregulation of 17 proteins, suggesting their therapeutic potential. Biomimicry of the fetal paracrine signature to reprogram macrophages and modulate inflammation could be an important future research direction for developing novel therapeutics.

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

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.

Acute Phase Proteins Are Baseline Predictors of Tuberculosis Treatment Failure

Systemic inflammation is a characteristic feature of pulmonary tuberculosis (PTB). Whether systemic inflammation is associated with treatment failure in PTB is not known. Participants, who were newly diagnosed, sputum smear and culture positive individuals with drug-sensitive PTB, were treated with standard anti-tuberculosis treatment and classified as having treatment failure or microbiological cure. The plasma levels of acute phase proteins were assessed at baseline (pre-treatment). Baseline levels of C-reactive protein (CRP), alpha-2 macroglobulin (a2M), Haptoglobin and serum amyloid P (SAP) were significantly higher in treatment failure compared to cured individuals. ROC curve analysis demonstrated the utility of these individual markers in discriminating treatment failure from cure. Finally, combined ROC analysis revealed high sensitivity and specificity of 3 marker signatures comprising of CRP, a2M and SAP in distinguishing treatment failure from cured individuals with a sensitivity of 100%, specificity of 100% and area under the curve of 1. Therefore, acute phase proteins are very accurate baseline predictors of PTB treatment failure. If validated in larger cohorts, these markers hold promise for a rapid prognostic testing for adverse treatment outcomes in PTB.