The immune response in horses involves a complex network of cells, tissues, and molecules that work together to protect the animal from pathogens and other harmful agents. This process includes both innate and adaptive immune mechanisms. Innate immunity provides the first line of defense and involves components such as physical barriers, phagocytic cells, and the complement system. Adaptive immunity, on the other hand, is characterized by the activation of lymphocytes and the production of antibodies, which provide a targeted response to specific antigens. Key components of the equine immune system include T cells, B cells, and various cytokines that facilitate communication between immune cells. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, regulation, and implications of immune responses in equine health.
Zarski LM, Vaala WE, Barnett DC, Bain FT, Soboll Hussey G.Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection-the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert I.N. (Flu Avert), which is known to stimulat...
Schnabel CL, Babasyan S, Freer H, Larson EM, Wagner B.Tumor necrosis factor-α (TNF-α) is a pleiotropic cytokine, that is involved in acute inflammation and is employed as a biomarker of inflammatory diseases in several species for which reliable quantification is available. We aimed to develop suitable tools to quantify TNF-α in equine samples. We generated two new mAbs against equine TNF-α (clones 48 and 292), evaluated their specificity for this cytokine, and confirmed detection of native TNF-α in stimulated equine PBMC. The TNF-α mAbs were paired in a fluorescent bead-based assay for quantification of equine TNF-α. The TNF-α assay had ...
Chen X, Zhao Y, Su L, Wang L, Ma X, Zhang B, Su Y.Strangles, which is caused by Streptococcus equi subspecies equi, is one of the most prevalent equine infectious diseases and poses heavy economic losses worldwide. Although various vaccines have been used for decades, they seemed to be sub-optimal to demonstrate effective protection, and the antigen component of vaccines against S. equi remains to be optimized. In the present study, three target antigens (M-like protein, α2-macroglobulin and IgG-binding protein, and glyceraldehyde-3-phosphate dehydrogenase) were selected and expressed. Mice were immunized and challenged, and their immune res...
Ibrahim S, Hedia M, Taqi MO, Derbala MK, Mahmoud KGM, Ahmed Y, Ismail S, El-Belely M.So far the intimate link between serum microRNA (miRNA) and uterine inflammation in mares is unknown. We aimed (I) to investigate expression profile of eca-miR-155, eca-miR-223, eca-miR-17, eca-miR-200a, and eca-miR-205 (II) and to measure concentrations of interleukin 6 (IL-6), and prostaglandins (PGF and PGE) in serum of mares with healthy and abnormal uterine status (endometritis). This study was conducted on 80 Arabian mares: young (4-7 years), and old (8-14 years). Mares were divided into 48 sub-fertile (endometritis) and 32 fertile (control) at stud farms. Serum was collected for measuri...
Dionísio L, Medeiros F, Pequito M, Faustino-Rocha AI.Influenza is an extremely contagious respiratory disease, which predominantly affects the upper respiratory tract. There are four types of influenza virus, and pigs and chickens are considered two key reservoirs of this virus. Equine influenza (EI) virus was first identified in horses in 1956, in Prague. The influenza A viruses responsible for EI are H7N7 and H3N8. Outbreaks of EI are characterized by their visible and rapid spread, and it has been possible to isolate and characterize H3N8 outbreaks in several countries. The clinical diagnosis of this disease is based on the clinical signs pre...
Mateo-Otero Y, Zambrano F, Catalán J, Sánchez R, Yeste M, Miro J, Fernandez-Fuertes B.In several mammalian species, acute endometritis driven by the recruitment of polymorphonuclear cells (PMN) occurs in response to semen. These PMNs release DNA to form neutrophil extracellular traps (NETs) in cattle, horse and human, leading to sperm entrapment. While there is no evidence of this phenomenon occurring in donkeys, artificial insemination (AI) with frozen-thawed semen, which results in very poor pregnancy rates, leads to a large PMN recruitment to the uterus. Objective: To investigate whether donkey semen can trigger NET release (NETosis) and if excessive NETosis occurs in respon...
Wong DM, Young L, Dembek KA.Sepsis is common in foals and several treatments are used to facilitate recovery. Evidence in people suggests an association between low blood concentrations of thiamine, ascorbic acid, and cortisol and sepsis, with further evidence suggesting that administration of hydrocortisone, thiamine, and ascorbic acid may improve outcome. No information is available with regard to these treatments in foals. Objective: To compare blood concentrations of thiamine, ascorbic acid, and cortisol in healthy and ill foals. Methods: Fifteen healthy and 27 ill (septic and sick-nonseptic [SNS]) foals were evaluat...
Raza F, Babasyan S, Larson EM, Freer HS, Schnabel CL, Wagner B.Interleukin-4 (IL-4) is a key cytokine secreted by type 2 T helper (Th2) cells that orchestrates immune responses during allergic reactions. Human and mouse studies additionally suggest that basophils have a unique role in the regulation of allergic diseases by providing initial IL-4 to drive T cell development towards the Th2 phenotype. Equine Culicoides hypersensitivity (CH) is a seasonal immunoglobulin E (IgE)-mediated allergic dermatitis in horses in response to salivary allergens from Culicoides (Cul) midges. Here, we analyzed IL-4 production in peripheral blood mononuclear cells (PBMC) o...
Bannai H, Takahashi Y, Ohmura H, Ebisuda Y, Mukai K, Kambayashi Y, Nemoto M, Tsujimura K, Ohta M, Raidal S, Padalino B.This study evaluated the effects of 12-hour transportation on immune responses to equine herpesvirus type 1 (EHV-1) and type 4 (EHV-4). Possible replication of EHV-1 and EHV-4 was monitored by real-time PCR of nasal swabs and peripheral blood mononuclear cells (PBMCs), and changes in systemic and mucosal antibodies were investigated. Six healthy Thoroughbreds with transport experience were transported in commercial trucks, repeating the same three-hour route four times. Blood samples for cortisol measurement were taken before departure and every three hours. Nasal swabs, PBMCs, nasal wash and ...
Pezzanite L, Chow L, Hendrickson D, Gustafson DL, Russell Moore A, Stoneback J, Griffenhagen GM, Piquini G, Phillips J, Lunghofer P, Dow S....Septic arthritis causes significant morbidity and mortality in veterinary and human clinical practice and is increasingly complicated by multidrug-resistant infections. Intra-articular (IA) antibiotic administration achieves high local drug concentrations but is considered off-label usage, and appropriate doses have not been defined. Using an equine joint model, we investigated the effects of amikacin injected at three different doses (500, 125, and 31.25 mg) on the immune and cartilage responses in tibiotarsal joints. Synovial fluid (SF) was sampled at multiple time points over 24 h, the cell...
Lindenberg FC, Lützhøft DO, Krych L, Fielden J, Kot W, Frøkiær H, van Galen G, Nielsen DS, Hansen AK.Some oligosaccharides induce growth of anti-inflammatory bacterial species and induce regulatory immunity in humans as well as animals. We have shown that the equine gut microbiota and the immune-microbial homeostasis largely stabilize within the first 50 days of life. Furthermore, we have previously established that certain bacterial species in the equine gut correlated with regulatory immunity. Accordingly, we hypothesized that an oligosaccharide rich diet fed to foals during the first 50 days would increase the abundance of bacterial species associated with regulatory immunity, and that thi...
Hedia M, Ibrahim S, Mahmoud K, Ahmed Y, Ismail S, El-Belely M.Apparently healthy mares with conception failure or embryonic loss may have subclinical endometritis (SE). Our objective was to document evidence of systemic immune responses against SE in mares. In apparently healthy (control) mares as well as those with chronic endometritis (ChE) or subacute suppurative endometritis (SSE), both considered classes of SE, serum concentrations of cytokines (IL-1β, IL-6, IL-10 and TNF), chemokines (IL-8), acute phase protein (SAA), and plasma concentrations of prostaglandins (PGF and PGE) were measured using validated enzyme linked immunoassays (EIA). Mixed-bre...
Larson EM, Wagner B.Horses have many naturally occurring diseases that mimic similar conditions in humans. The ability to conduct environmentally controlled experiments and induced disease studies in a genetically diverse host makes the horse a valuable intermediate model between mouse studies and human clinical trials. This review highlights important similarities in the immune landscape between horses and humans using current research on two equine diseases as examples. First, equine herpesvirus type 1 (EHV-1) infection initiates a series of innate inflammatory signals at its mucosal entry site in the upper res...
El-Sheikh Ali H, Scoggin KE, Ruby R, Loynachan A, Boakari Y, Fernandes C, Dini P, Fedorka CE, Loux SC, Esteller-Vico A, Ball BA.Cervical remodeling is a critical component in both term and preterm labor in eutherian mammals. However, the molecular mechanisms underlying cervical remodeling remain poorly understood in the mare. The current study compared the transcriptome of the equine cervix (cervical mucosa (CM) and stroma (CS)) during placentitis (placentitis group, n = 5) and normal prepartum mares (prepartum group, n = 3) to normal pregnant mares (control group, n = 4). Transcriptome analysis identified differentially expressed genes (DEGs) during placentitis (5310 in CM and 907 in CS) and during the normal prepartu...
Larson EM, Babasyan S, Wagner B.IL-8 is a potent chemokine that recruits neutrophils and basophils to promote inflammation in many species. IL-8 is produced by many cell types, including monocytes. In this study, we report a novel role for IgE-binding monocytes, a rare peripheral immune cell type, to promote allergic inflammation through IL-8 production in a horse model of natural IgE-mediated allergy. We developed a mAb with confirmed specificity for both recombinant and native equine IL-8 for flow cytometric analysis. Equine IL-8 was produced by CD14/MHC class II/CD16 monocytes, including a subpopulation of IgE-binding mon...
Sullivan E, Lecollinet S, Kerviel A, Hue E, Pronost S, Beck C, Dumarest M, Zientara S, Roy P.African horse sickness virus (AHSV) is an Orbivirus within the Reoviridae family, spread by Culicoides species of midges, which infects equids with high mortality, particularly in horses and has a considerable impact on the equine industry. In order to control the disease, we previously described Entry Competent Replication Abortive (ECRA) virus strains for each of the nine distinct AHSV serotypes and demonstrated their potential as vaccines, first in type I interferon receptor (IFNAR-/-) knockout mice, and then in ponies. In this report we have investigated whether or not a combination ECRA v...
Onzere CK, Fry LM, Bishop RP, Silva MG, Bastos RG, Knowles DP, Suarez CE.Theileria equi is a widely distributed apicomplexan parasite that causes severe hemolytic anemia in equid species. There is currently no effective vaccine for control of the parasite and understanding the mechanism that T. equi utilizes to invade host cells may be crucial for vaccine development. Unlike most apicomplexan species studied to date, the role of micronemes in T. equi invasion of host cells is unknown. We therefore assessed the role of the T. equi claudin-like apicomplexan microneme protein (CLAMP) in the invasion of equine erythrocytes as a first step towards understanding the role...
Segabinazzi LGTM, Canisso IF, Podico G, Cunha LL, Novello G, Rosser MF, Loux SC, Lima FS, Alvarenga MA.Microorganisms, including pathogenic or opportunistic bacteria and fungi, may gain access to the uterus during breeding, and infectious endometritis plays a major role in equine subfertility. This study aimed to assess the post-breeding inflammatory response, endometrial culture, and embryo recovery of mares susceptible to persistent breeding-induced endometritis (PBIE) treated with plasma-rich (PRP) or -poor (PPP) plasma. Mares (n = 12) susceptible to PBIE had three cycles randomly assigned to receive intrauterine infusions of lactate ringer solution (LRS, control), or autologous PRP or PPP p...
Kushugulova A, Löber U, Akpanova S, Rysbekov K, Kozhakhmetov S, Khassenbekova Z, Essex M, Nurgozhina A, Nurgaziyev M, Babenko D, Markó L....Probiotics and prebiotics are widely used for recovery of the human gut microbiome after antibiotic treatment. High antibiotic usage is especially common in children with developing microbiome. We hypothesized that dry Mare's milk, which is rich in biologically active substances without containing live bacteria, could be used as a prebiotic in promoting microbial diversity following antibiotic treatment in children. The present pilot study aims to determine the impacts of dry Mare's milk on the diversity of gut bacterial communities when administered during antibiotic treatment and throughout ...
Muko R, Matsuda H, Oikawa MA, Shin T, Matsuda K, Sato H, Sunouchi T, Tanaka A.Histidine-rich glycoprotein (HRG) is an abundant plasma protein that has been identified in most mammals. We first identified whole genome sequence of equine HRG (eHRG) and succeeded to purify eHRG from plasma of horses. Since HRG interacts with various ligands, this protein is thought to be involved in immune response, coagulation, and angiogenesis. Systemic inflammatory response syndrome (SIRS) is characterized as a non-specific, clinical, pro-inflammatory immune response that damage organs and tissues in the host. Recent reports revealed that blood HRG levels in human patients with SIRS are...
Picetti TS, Soveral LF, Miotto R, Erpen LMS, Kreutz Y, Guizzo JA, Frandoloso R, Kreutz LC.Immune-modulating molecules mainly act on innate immune cells, which are central to early defense against invading pathogens and contribute to developing adaptive immunity. Yeast-extracted β-glucan, a model immune-modulating molecule, is widely used in several animal species; however, its effect on horse immune parameters has not been thoroughly investigated yet. This study aimed to evaluate the effects of orally administered β-glucan on selected innate immune parameters in horses. Methods: Eighteen thoroughbred horses were assigned equally into three groups as follows: One control group (no...
Slowikowska M, Bajzert J, Miller J, Stefaniak T, Niedzwiedz A.Non-invasive diagnostic biomarkers of equine asthma syndrome (EAS) from blood or urine are sought. The aim of this study was to assess the absorbance of circulating immune complexes (CICs) during the exacerbation, remission, and treatment of an asthma episode and assess the potential usefulness of CIC levels in the diagnosis and monitoring of the disease. The control group, asthma group, and treated asthma group each contained six horses. Following an initial examination and group classification, the horses were kept in a dusty environment for seven days and then moved to an asthma-friendly en...
Wall GV, Wright IM, Barnardo C, Erasmus BJ, van Staden V, Potgieter AC.African horse sickness virus (AHSV) non-structural protein NS4 is a nucleocytoplasmic protein that is expressed in the heart, lung, and spleen of infected horses, binds dsDNA, and colocalizes with promyelocytic leukemia nuclear bodies (PML-NBs). The aim of this study was to investigate the role of AHSV NS4 in viral replication, virulence and the host immune response. Using a reverse genetics-derived virulent strain of AHSV-5 and NS4 deletion mutants, we showed that knockdown of NS4 expression has no impact in cell culture, but results in virus attenuation in infected horses. RNA sequencing (RN...
Faber E, Tshilwane SI, Kleef MV, Pretorius A.African horse sickness (AHS) is caused by African horse sickness virus (AHSV), a double stranded RNA (dsRNA) virus of the genus Orbivirus, family Reoviridae. For the development of new generation AHS vaccines or antiviral treatments, it is crucial to understand the host immune response against the virus and the immune evasion strategies the virus employs. To achieve this, the current study used transcriptome analysis of RNA sequences to characterize and compare the innate immune responses activated during the attenuated AHSV serotype 4 (attAHSV4) (in vivo) and the virulent AHSV4 (virAHSV4) (in...
Tongu EAO, Segabinazzi LGTM, Alvarenga ML, Monteiro A, Papa FO, Alvarenga MA.This study aimed to evaluate the effects of mesenchymal stem cell-conditioned medium (MSC-CM) on sperm parameters, intrauterine polymorphonuclear neutrophils (PMN), intrauterine fluid accumulation (IUF), and fertility in mares. In experiment 1, two ejaculates from ten stallions were extended to 50 million sperm/mL using a milk-based extender. Thereafter, 20 mL of extended semen was added of MSC-CM as follows: 0, 5, 10, 15, and 20 mL. Sperm kinetics and plasma membrane integrity were evaluated immediately after dilution (T0) and 2 h post-incubation at 37 °C (T2). In experiment 2, mares cha...
Cequier A, Sanz C, Rodellar C, Barrachina L.The differentiation ability of mesenchymal stem cells (MSCs) initially raised interest for treating musculoskeletal injuries in horses, but MSC paracrine activity has widened their scope for inflammatory and immune-mediated pathologies in both equine and human medicine. Furthermore, the similar etiopathogenesis of some diseases in both species has advanced the concept of "One Medicine, One Health". This article reviews the current knowledge on the use of MSCs for equine pathologies beyond the locomotor system, highlighting the value of the horse as translational model. Ophthalmologic and repro...
Zilch TJ, Lee JJ, Saleem MZ, Zhang H, Cortese V, Voris N, McDonough SP, Divers TJ, Chang YF.Little information is available about experimental inoculation of leptospirosis in horses and the pathogenicity of Leptospira interrogans serovar Bratislava in this host. Objective: To determine the serological, clinical, pathological and haematological responses of horses to L. interrogans serovar Bratislava strain PigK151. Methods: Randomised controlled in vivo experiment. Methods: Ten seronegative female foals were divided into 2 groups, control (n = 4) and challenged (n = 6). The challenged group received 1 × 109 leptospires divided equally between topical ocular and intraperitoneal...
Collinet A, Grimm P, Julliand S, Julliand V.The equine hindgut ecosystem is specialized in dietary fibers' fermentation to provide horses' energy and contribute to its health. Nevertheless, antibiotics are known to disrupt the hindgut microbiota, affecting the fibrolytic activity of bacteria and the intestinal immune balance, leading to diseases. This study used a general and comprehensive approach for characterizing the hindgut ecosystem of 9 healthy horses over 28 days in response to a 5-day challenge with oral trimethoprim-sulfadiazine (TMS), with a special emphasis on microbial fibrolytic activity and the host immune response. Hors...
Kalpokas I, Martínez MN, Cavestany D, Perdigón F, Mattos RC, Meikle A.We investigated the early effects of the equine embryo on maternal serum concentrations of insulin-like growth factor 1 (IGF1), leptin and adiponectin, uterine immune cells and genes and proteins related to embryo development and the maintenance of pregnancy. Ipsilateral endometrial expression was assessed on Days 7 and 13 after ovulation for the following transcripts: oestrogen receptor ERα (ESR1), progesterone receptor (PGR), progestin and adipoQ receptor family member 5 (PAQR5), oxytocin receptor (OXTR), prostaglandin-endoperoxide synthase 2 (PTGS2), raf-1 proto-oncogene serine/threonine k...
Boyle AG, Mitchell C, Stefanovski D, Waller AS.The dual antigen iELISA uses two Streptococcus equi subsp equi surface protein antigens composed of N-terminal portions of SEQ2190 (Antigen A) and SeM (Antigen C). It is currently used to identify animals exposed to S. equi which have developed an immune response to the target antigens. Objective: To determine the usefulness of the dual antigen iELISA in a population of horses vaccinated with Pinnacle IN. We hypothesised that horses vaccinated for strangles with a live attenuated, non-encapsulated SeM-2 strain of S. equi, would seroconvert when tested 5 weeks later by the dual antigen iELIS...
Dirscherl P, Grabner A, Buschmann H.As basophils are the major effector cells of allergic reactions, confirmation of the allergic etiology of chronic obstructive pulmonary disease (COPD) was sought by the demonstration of a specific in vitro response of equine basophilic blood cells to some potential allergens (Aspergillus, Cladosporidium, Mucor, Penicillium, extracts of dust particles of hay and straw). The allergen induced degranulation of basophils and the histamine and protease release from basophils during incubation with the allergens were tested. By evaluating the results obtained from 14 COPD horses and eight controls it...
Knowles DP.Infection of horses with the hemoprotozoan Babesia equi has been reported in southern Florida, US Virgin Islands, part of Asia, Russia, India, the Middle East, Europe, Africa, Australia, South America, Central America, Mexico, Philippine Islands and some Caribbean islands. The restrictions placed on the international movement of infected horses has refocused attention on potential methods to control or eliminate infection. Don Knowles here discusses the primary chemotherapeutic compounds that have been used; the current knowledge concerning immune responses that potentially contribute to contr...
Hemphill DD, McIlwraith CW, Samulski RJ, Goodrich LR.Adeno-associated virus (AAV) receptors range from heparan sulfate proteoglycan to sialic acid moieties present on cell surfaces. Abundance of the glycan profiles is greatly influenced by animal species, cell type, and culture conditions. The objective of this study was to determine whether AAV serotypes' transduction efficiencies specifically in the equine monolayer culture model are an accurate representation of transduction efficiencies in tissue explants, a model more closely related to in vivo transduction. It was found that AAV 2 and 2.5 transduced cells more efficiently in explants than ...
Hernández JÁ, Arroyo FL, Suárez J, Cazapal-Monteiro CF, Romasanta Á, López-Arellano ME, Pedreira J, de Carvalho LMM, Sánchez-Andrade R....The usefulness of pellets industrially manufactured with spores of parasiticide fungi as a contribution to integrated nematode control was assessed in grazing horses throughout sixteen months. Two groups of 7 Pura Raza Galega autochthonous horses (G-T and G-P) were dewormed pour-on (1mg Ivermectin/kg bw) at the beginning of the trial, and other group (G-C) remained untreated. The G-P was provided daily with commercial pellets to which was added a mixture of fungal spores during the industrial manufacturing (2×10 spores of Mucor circinelloides and same dose of Duddingtonia flagrans/kg), and G-...
Wilkie BN.Effective resistance to respiratory tract infection depends principally on specific immunity on mucosal surfaces of the upper or lower respiratory tract. Respiratory tract immune response comprises antibody and cell-mediated systems and may be induced most readily by surface presentation of replicating agents but can result from parenteral or local presentation of highly immunogenic antigens. Upper and lower respiratory tract systems differ in immunologic competence, with the lungs having a greater inventory of protective mechanisms than the trachea or nose. Several effective vaccines have bee...
Guss B, Flock M, Frykberg L, Waller AS, Robinson C, Smith KC, Flock JI.Streptococcus equi subspecies equi (S. equi) is a clonal, equine host-adapted pathogen of global importance that causes a suppurative lymphodendopathy of the head and neck, more commonly known as Strangles. The disease is highly prevalent, can be severe and is highly contagious. Antibiotic treatment is usually ineffective. Live attenuated vaccine strains of S. equi have shown adverse reactions and they suffer from a short duration of immunity. Thus, a safe and effective vaccine against S. equi is highly desirable. The bacterium shows only limited genetic diversity and an effective vaccine coul...
Little D, Tomlinson JE, Blikslager AT.Post operative ileus (POI) remains an important cause of post operative morbidity and mortality in the horse. However, clinical progression of naturally occurring cases of POI in both horse and man does not entirely support the 'neurogenic' hypothesis as the sole mechanism of POI; and the hypothesis that inflammation plays a major role at 12-24 h after surgery requires validation. Objective: An inflammatory infiltrate in the muscularis externa and myenteric plexus of equine jejunum is present 18 h following a period of ischaemia. Methods: Samples of normal jejunum, jejunum from the proximal re...
Schnabel CL, Wemette M, Babasyan S, Freer H, Baldwin C, Wagner B.Chemokines are soluble molecules directing immune cell trafficking and homing, mediating inflammation, and initiating immune responses to infection. In horses, the analysis of chemokines has been limited by the lack of specific antibodies. We generated mAbs specific for the equine C-C motif chemokine ligands (CCL) CCL2 (MCP-1), CCL3 (MIP-1α), CCL5 (RANTES) and CCL11 (eotaxin) using hybridoma technology. Antibody specificity was confirmed by intracellular staining of Chinese Hamster Ovary cells transfected with expression vectors encoding for CCL2, CCL3, CCL5, or CCL11. Transfectants were stai...
Naskou MC, Norton NA, Copland IB, Galipeau J, Peroni JF.Platelet lysate (PL) has been extensively used for the laboratory expansion of human mesenchymal stem cells (MSC) in order to avoid fetal bovine serum (FBS) which has been associated with immune-mediated host reactions and transmission of bovine-origin microbial contaminants. Before suggesting the routine use of PL for MSC culture, we wanted to further investigate whether PL alone might trigger inflammatory responses when exposed to reactive white blood cells such as monocytes. Our objectives were to evaluate the inflammatory profile of equine monocytes cultured with equine PL (ePL) and to det...
Scharrenberg A, Gerber V, Swinburne JE, Wilson AD, Klukowska-Rötzler J, Laumen E, Marti E.Equine recurrent airway obstruction (RAO) is a chronic lower airway disease of the horse caused by hypersensitivity reactions to inhaled stable dust, including mould spores such as Aspergillus fumigatus. The goals of this study were to investigate whether total serum IgE levels and allergen-specific IgE and IgG subclasses are influenced by genetic factors and/or RAO and whether quantitative trait loci (QTL) could be identified for these parameters. The offspring of two RAO-affected sires (S1: n=56 and S2: n=65) were grouped by stallion and disease status, and total serum IgE levels and specifi...
Morris DD, Crowe N, Moore JN.Serum tumor necrosis factor (TNF) activity was quantitated in 8 horses given an IV infusion of endotoxin (0.03 micrograms of lipopolysaccharide/kg of body weight, from Escherichia coli 055:B5) in 0.9% NaCl solution over 1 hour. Serum TNF activity was likewise measured in 6 horses given only 0.9% sterile NaCl solution at the same rate. The duration of serum TNF activity was determined, and serum TNF activity was correlated with clinical and laboratory changes during the induced endotoxemia. Horses had no serum TNF activity prior to endotoxin administration, but geometric mean serum TNF activity...
Estrada McDermott J, Pezzanite L, Goodrich L, Santangelo K, Chow L, Dow S, Wheat W.Osteoarthritis (OA) is a common condition with diverse etiologies, affecting horses, humans, and companion animals. Importantly, OA is not a single disease, but rather a disease process initiated by different events, including acute trauma, irregular or repetitive overload of articular structures, and spontaneous development with aging. Our understanding of the pathogenesis of OA is still evolving, and OA is increasingly considered a multifactorial disease in which the innate immune system plays a key role in regulating and perpetuating low-grade inflammation, resulting in sustained cartilage ...
Finno CJ, Gianino G, Perumbakkam S, Williams ZJ, Bordbari MH, Gardner KL, Burns E, Peng S, Durward-Akhurst SA, Valberg SJ.The cause of immune-mediated myositis (IMM), characterized by recurrent, rapid-onset muscle atrophy in Quarter Horses (QH), is unknown. The histopathologic hallmark of IMM is lymphocytic infiltration of myofibers. The purpose of this study was to identify putative functional variants associated with equine IMM. A genome-wide association (GWA) study was performed on 36 IMM QHs and 54 breed matched unaffected QHs from the same environment using the Equine SNP50 and SNP70 genotyping arrays. A mixed model analysis identified nine SNPs within a ~ 2.87 Mb region on chr11 that were significantly (...
Marchetti B, Gault EA, Cortese MS, Yuan Z, Ellis SA, Nasir L, Campo MS.Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 c...
Schmidt NJ, Melnick JL, Wenner HA, Ho HH, Burkhardt MA.Immune horse sera to 42 enterovirus immunotypes were pooled according to the Lim Benyesh-Melnick and the "intersecting serum" schemes. Each serum was diluted in the pools to contain 50 antibody units. After it was established that the pools correctly neutralized prototype virus strains, they were evaluated in tests against 273 enterovirus field strains representing most of the viral types included in the pools. With test virus doses of 10-100 TCD(50), most of the poliovirus and coxsackievirus field strains were correctly identified in both schemes, but a number of the echoviruses were neutrali...
Balasuriya UB.Equine arteritis virus (EAV), the causative agent of equine viral arteritis (EVA), is a respiratory and reproductive disease that occurs throughout the world. EAV infection is highly species-specific and exclusively limited to members of the family Equidae, which includes horses, donkeys, mules, and zebras. EVA is an economically important disease and outbreaks could cause significant losses to the equine industry. The primary objective of this article is to summarize current understanding of EVA, specifically the disease, pathogenesis, epidemiology, host immune response, vaccination and treat...
Moore BD, Balasuriya UB, Watson JL, Bosio CM, MacKay RJ, MacLachlan NJ.Equine arteritis virus (EAV) infects endothelial cells (ECs) and macrophages in horses, and many of the clinical manifestations of equine viral arteritis (EVA) reflect vascular injury. To further evaluate the potential role of EAV-induced, macrophage-derived cytokines in the pathogenesis of EVA, we infected cultured equine alveolar macrophages (AMphi), blood monocyte-derived macrophages (BMphi), and pulmonary artery ECs with either a virulent (KY84) or an avirulent (CA95) strain of EAV. EAV infection of equine AMphi, BMphi, and ECs resulted in their activation with increased transcription of g...
Miller RI, Campbell RS.One in vivo and 2 in vitro tests were developed to study immunological aspects of phycomycosis in clinically infected, recovered and normal in-contact horses. Serum from all infected horses gave positive readings in an agar-gel double diffusion test; serum from normal and recovered horses did not react. A complement fixation test detected antibody against Hyphomyces destruens in 82% clinical cases at an average titre of 20. Serum from recovered and in-contact horses reacted sporadically at positive titre. An intradermal hypersensitivity test (Heaf test) was used to detect evidence of cellular ...
Segabinazzi LG, Friso AM, Correal SB, Crespilho AM, Dell'Aqua JA, Miró J, Papa FO, Alvarenga MA.Persistent mating-induced endometritis (PMIE) results in decreased fertility in horses, thereby causing a significant impact in the horse market. Platelet-rich plasma (PRP), a modulator of the inflammatory response, has been largely used in veterinary medicine. Here, we investigated the effects of PRP on uterine inflammation, conception rate, endometrial polymorphonuclear neutrophil (PMN) migration, and COX-2 protein levels in the endometrial tissue. Thirteen PMIE-susceptible mares were used for artificial insemination (AI). The mares were inseminated with fresh semen in three consecutive cycl...
Miller AB, Loynachan AT, Bush HM, Hart KA, Barker VD, Campana-Emard AG, Grubbs ST, Adams AA.It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulat...
Slater JD, Gibson JS, Field HJ.Both intranasal (i.n.) and intracerebral (i.c.) inoculation of mice with wild-type equine herpesvirus type 1 (wt EHV-1) caused clinical signs and mortality. Virus could be recovered from target organs (turbinates, lungs and blood) for several days. By contrast, the thymidine kinase (TK)-deficient deletion mutant PR1 produced markedly less clinical disease following both i.n. and i.c. inoculation, and, in particular, no mortality occurred. PR1 did, however, establish productive infections following either route of inoculation. High titres of virus were recovered from target organs although viru...
Kim HY, Mott J, Zhi N, Tajima T, Rikihisa Y.Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected...
Aksular M, Calvo-Pinilla E, Marín-López A, Ortego J, Chambers AC, King LA, Castillo-Olivares J.African horse sickness is a severe, often fatal, arboviral disease of equids. The control of African horse sickness virus (AHSV) in endemic countries is based currently on the use of live attenuated vaccines despite some biosafety concerns derived from its biological properties. Thus, experimental vaccination platforms have been developed over the years in order to avoid the biosafety concerns associated with the use of attenuated vaccines. Various studies showed that baculovirus-expressed AHSV-VP2 or modified Vaccinia Ankara virus expressing AHSV-VP2 (MVA-VP2) induced virus neutralising antib...
Klier J, May A, Fuchs S, Schillinger U, Plank C, Winter G, Gehlen H, Coester C.Recurrent airway obstruction (RAO) in horses has become a common problem in stabled horses in industrialized countries and deserves new therapeutic strategies. CpG-oligodeoxynucleotides (CpG-ODNs) were developed as effective immunostimulating agents to induce a Th2/Th1 shift. These agents showed a beneficial therapeutic effect in allergic diseases with predominant Th2 immunoresponse. CpG-ODN delivery by gelatin nanoparticles (GNPs) resulted in enhanced cellular uptake in murine and human in vitro studies and was a starting point for the present trial. The aim of this study was to identify an o...
Karagianni AE, Kapetanovic R, Summers KM, McGorum BC, Hume DA, Pirie RS.Alveolar macrophages (AMs) are the first line of defence against pathogens in the lungs of all mammalian species and thus may constitute appropriate therapeutic target cells in the treatment and prevention of opportunistic airway infections. Therefore, acquiring a better understanding of equine macrophage biology is of paramount importance in addressing this issue in relation to the horse. Objective: To compare the transcriptome of equine AMs with that of equine peritoneal macrophages (PMs) and to investigate the effect of lipopolysaccharide (LPS) on equine AM. Methods: Gene expression study o...
Berndt A, Derksen FJ, Venta PJ, Ewart S, Yuzbasiyan-Gurkan V, Robinson NE.Recurrent airway obstruction (RAO) is characterized by neutrophilic airway inflammation and obstruction, and stabling of susceptible horses triggers acute disease exacerbations. Stable dust is rich in endotoxin, which is recognized by Toll-like receptor (TLR) 4. In human bronchial epithelium, TLR4 stimulation leads to elevation of interleukin (IL)-8 mRNA expression. The zinc finger protein A20 negatively regulates this pathway. We hypothesized that TLR4 and IL-8 mRNA and neutrophil numbers are elevated and that A20 mRNA is not increased in RAOs during stabling compared with controls and with R...
Cequier A, Vázquez FJ, Romero A, Vitoria A, Bernad E, García-Martínez M, Gascón I, Barrachina L, Rodellar C.The immunomodulatory properties of equine mesenchymal stem cells (MSCs) are important for their therapeutic potential and for their facilitating role in their escape from immune recognition, which may also be influenced by donor-recipient major histocompatibility complex (MHC) matching/mismatching and MHC expression level. Factors such as inflammation can modify the balance between regulatory and immunogenic profiles of equine MSCs, but little is known about how the exposure to the immune system can affect these properties in equine MSCs. In this study, we analyzed the gene expression and secr...
Cullinane A, Gildea S, Weldon E.Vaccination is crucial to the control of equine influenza (EI). The study was conducted in an effort to lay the groundwork for achieving international harmonisation of regulatory requirements based on scientific evidence of performance of different vaccination regimes. Objective: To evaluate the effectiveness of 3 different primary vaccination regimes: vaccination with the minimal intervals permitted by the racing authorities; vaccination in accordance with the manufacturer's instructions and vaccination with the longest intervals permitted by the racing authorities. Methods: Randomised, prosp...
Loftus JP, Black SJ, Pettigrew A, Abrahamsen EJ, Belknap JK.To determine proinflammatory gene expression, endothelial adhesion molecule gene expression, and matrix metalloproteinase (MMP) concentrations in laminar specimens at 1.5 hours after administration of black walnut extract (BWE) and to compare these values with later time points. Methods: 25 horses. Methods: After nasogastric administration of BWE, anesthesia was induced at 1.5 hours in early time point (ETP) horses (n = 5), between 3 and 4 hours in developmental time point horses (5), and between 9 and 10 hours in acute onset of lameness time point horses (5). Anesthesia was induced at 3 and 1...
Nyindo MB, Ristic M, Lewis GE, Huxsoll DL, Stephenson EH.Four ponies experimentally infected with Ehrlichia equi developed substantial cell-mediated immune responses, as measured by the leukocyte migration-inhibition test. Serum anti-E equi antibodies up to 1:1,280 were demonstrated by the indirect fluorescent antibody test. Cell-mediated immune responses returned to a base-line value by day 200 after primary inoculation, but serum antibody titers persisted for at least 300 days after inoculation. Two additional susceptible ponies, which were inoculated with convalescent blood or organ homogenates from ponies recovered from acute equine ehrlichiosis...
