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.
Rodrigues MF, Neves AP, Ferreira R, Pessoa GA, Araujo DN, de Souza GV.Melatonin has demonstrated beneficial effects in regulating inflammatory processes in various tissues, but its role in mare uterine physiology remains unclear. Objective: To investigate the effects of melatonin on the gene expression of cytokines (IL-1β, IL-6, IL-8, IL-10, and TNF-α) in equine uterine explants cultured for 6, 12, or 24 hours. Methods: The study was divided into two experiments. Part 1 aimed to evaluate the cytotoxicity of melatonin at concentrations of 0, 0.5, 1, 2, 4, and 8 mM on endometrial cells. Part 2 aimed to determine the expression of inflammatory cytokines in uterin...
Epizootic lymphangitis (EEL), caused by Histoplasma capsulatum var. farciminosum (HCF), is a neglected equine fungal disease lacking effective vaccines. The newly developed inactivated '8ZH' vaccine requires safety validation in the target species. Objective: To evaluate the biochemical, haematological and clinical safety of the inactivated HCF '8ZH' vaccine in foals. Methods: A controlled, single-blinded study was conducted on 30 clinically healthy foals (4-6 months), randomized into vaccinated (n = 15) and control (n = 15) groups. Vaccinated animals received a 5 mL intramuscular dose (...
Cooper CJ, Arroyo LG, Hammermueller JD, Botts MM, Pearl DL, Wootton SK, Lillie BN.Equine herpesvirus-1 (EHV-1) is ubiquitous in the horse population, but prevalence estimates have ranged from 3 to 88% depending on the population and method of sampling. No prevalence studies have been carried out in Ontario, Canada. The objective of this study was to measure the prevalence of EHV-1 shedding in healthy broodmares in Ontario. A total of 381 mares from 42 farms in Ontario were sampled, including pregnant and barren broodmares. Samples were collected from the nose, vagina, and blood of each mare up to 6 times from December 2016 through October 2017 using a cross-sectional study ...
Eskandari G, Ahmadi Sheikhsarmast S, Ghasemi S, Mohri M.Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein involved in immune responses and inflammation, with established diagnostic utility in acute kidney injury (AKI) and systemic diseases. However, reference values for NGAL in healthy horses, particularly the Turkmen breed, remain poorly defined. Objective: This study aimed to establish reference values for serum NGAL concentrations in healthy Turkmen horses and to evaluate the influence of age, sex, pregnancy status and physical activity on its levels, as well as its correlations with haematological and serum biochemical variabl...
Jager MC, Luethy D, Shallop S, Cathcart J, Divers TJ, Tan JY, Beasley EM, Johnson P, Leduc L, Smith C, Jamieson CA, Magdesian KG, Van de Walle GR....Equine hepacivirus (EqHV) is closely related to hepatitis C virus (HCV), which causes persistent infection and chronic hepatitis in people. Information on persistent EqHV infection and hepatitis is limited. Objective: To report 19 cases of chronic hepatitis and persistent EqHV infection. Methods: Mixed retrospective and prospective case series. Methods: Inclusion criteria were: (1) chronic hepatitis, defined as persistently increased serum liver biomarkers, increased serum liver biomarkers accompanied by histopathological evidence of chronicity, for example, fibrosis, or both; (2) positive ser...
Wang C, Wang J, Ma B, Liu T, Yuan X, Meng J, Zeng Y.: This study investigated the effects of dietary bamboo leaf extract (BLE) on milk parameters and intestinal microbiota in lactating mares. : Twenty-four mares of similar age (10 ± 2 years), weight (360.62 ± 15.23 kg) and body condition were selected for this study and randomly divided into four groups of six mares each: an untreated control group (CG) and three experimental groups (EG1, EG2, EG3) were fed a basal diet supplemented with 0, 10, 20, or 30 g/day of BLE, respectively, for 60 days. Then, horse milk composition, antioxidant activity, and immunoglobulin levels along with the rela...
Semanchik PL, Wesolowski LT, Artman JL, Seward RL, Beer C, Barnes ED, White-Springer SH.Reactive oxygen species are normal by-products of cellular metabolism but may have detrimental effects on cellular matrices and excite inflammatory pathways when overproduced. To test the hypothesis that supplementation of an herbal extract combination would: 1) improve antioxidant status; 2) increase anti-inflammatory cytokines; and 3) decrease pro-inflammatory cytokines, 40 mature, sedentary stock-type horses (32 mares, 8 geldings, mean±SD; 15.7 ± 4.9 yr, 519 ± 46 kg) were stratified by age, sex, and body weight and randomly assigned to one of four dietary treatment groups for 5...
Rask E, Righetti F, Ruiz A, Bjerketorp J, Frosth S, Frykberg L, Jacobsson K, Guss B, Flock JI, Henriques-Normark B, Hartman E, Gustafsson A....Infection of susceptible horses with subspecies (), the causative agent of strangles, is associated with commingling. Exposure may occur among horses at equestrian events, sales, or horses moved among different equine stabling environments. Strangles can affect all horses on a farm, leading to the death of up to 10% of cases depending on their immunity status at the time of infection, the development of complications, the success of biosecurity measures, and the use of vaccination. The current retrospective study used ELISAs to measure the exposure of horses to at a farm that experienced an...
Deniz Ö, Erol HS, van den Hoven R, Onmaz AC, Aragona F, Fazio F.Weaning represents a major developmental milestone for foals, especially when 4- to 7-month-old foals are abruptly separated from their dams. Studies have shown that the post-weaning period is associated with physiological and psychological stress, which may affect immune function. The present study aimed to describe and analyze the pattern of blood inflammatory biomarkers related to the innate immune system. A gradual foal-dam separation procedure was chosen, which included post-weaning social buffering by a familiar adult horse. Twelve Thoroughbred foals (six fillies, six colts) aged 4-6 mon...
El-Geneady MA, Ramadan RM, Mahdy OA, Kamel MS, Salem MA.Hippobosca equina, a common ectoparasite of horses, poses a significant challenge to equine health worldwide. This study provides a molecular characterization of H. equina and examines its impact on host immune responses and oxidative stress. Genetic analysis of samples from various regions revealed notable homogeneity, indicating limited genetic variation among populations. Phylogenetic analysis demonstrated close genetic relationships among sequences from Egypt, France, Kazakhstan and Portugal, while also showing comparable but more distant identities to sequences from China, Denmark, Finlan...
Jandová V, Huber N, AlMheiri FG, Bábor K, Trachsel DS.Stress represents a serious health and welfare concern; however, its objective assessment remains difficult. The equine gastric ulcer syndrome (EGUS) and orthopedic diseases that cause pain are among stress associated diseases in equine medicine. The leukocyte coping capacity (LCC) quantifies oxygen radical generation of neutrophil granulocytes which is altered under stress. Therefore, LCC could be a novel biomarker for stress in horses and we hypothesized that horses with stress associated diseases would have lower LCC values in comparison to horses without these diseases. Methods: In this ob...
Bhat S, Karunakaran S, Frossard JP, Choudhury B, Steinbach F.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, a notifiable respiratory and reproductive disease of equids that causes significant losses to the equine industry. This study presents a comprehensive analysis of two EAV outbreaks in the UK in 2019, combining virus isolation, sequencing and phylogenetic analysis to provide a holistic understanding of EAV dynamics in these outbreaks. Genetic characterization revealed that all outbreak strains were similar to viruses detected in the UK and Europe from 2004 to 2011, belonging to phylogroup D and clustering in two grou...
Schank N, Cottone A, Wulf M, Seiter K, Thomas B, Miller LMJ, Anderson SL, Sahyoun A, Abidi AH, Kassan M, Verma A.Equine colic remains a prevalent and potentially life-threatening condition with multifactorial origins, including dietary imbalances, stress, and microbial dysbiosis. Central to equine gut health is the production of short-chain fatty acids (SCFAs), primarily acetate, propionate, and butyrate, generated through microbial fermentation of dietary fibers in the hindgut. These metabolites not only serve as vital energy sources but also play crucial roles in maintaining intestinal barrier integrity, modulating motility, and suppressing inflammation. This review explores the role of SCFAs in equine...
Cooper BL, Hobbs KJ, Bayless R, Stinson-Miller A, Gruber E, Hepworth-Warren K, Lavoie JP, Sheats MK.Severe equine asthma (sEA) is characterized by increased lower airway neutrophils that contribute to dysregulated inflammation through the release of cytokines, reactive oxygen species and neutrophil extracellular traps (NETs). NETs are composed of cell-free DNA (cfDNA) intercalated with enzymatic proteins and are known to be increased in the lower airway of asthmatic horses. The objectives of this study were two-fold: 1. Determine if cfDNA can be accurately measured in equine bronchoalveolar lavage fluid (BALF) and tracheal wash (TW) with a Qubit 4 fluorometer. 2. Determine whether Qubit-meas...
Mules (Equus mulus), as sterile hybrids between mares and donkeys, present a unique uterine morphology and physiology that remains poorly characterized. This study provides the first histomorphometric evaluation and transcriptional profiling of the endometrium in adult mules. To achieve this, endometrial biopsies were analysed using quantitative stereology, histological classification (Kenney-Doig system), and qPCR of key immune-related and fibrotic genes. Histometric analyses revealed that the stratum spongiosum was the predominant component of the mule endometrium (mean volume density: 84.7...
Costa VMD, de Aguiar Filho RN, Braz GF, Paz CFR, Drumond BP, Teixeira BM, Kroon EG.Equine infectious anemia (EIA) is a chronic disease caused by the equine infectious anemia virus (EIAV), a member of the Retroviridae family and the Lentivirus genus. Most infected animals are asymptomatic carriers, which makes clinical diagnosis challenging. This study aimed to conduct a clinical and laboratory evaluation of EIA in equids used for equestrian tourism in Jericoacoara National Park, Ceará, Brazil. A total of 112 equids (104 horses and 8 mules) underwent clinical, hematological, biochemical, serological, and molecular assessments. The EIAV seropositivity rates were 11.6% by AGID...
Clark KF, Lemcke RA, Gasiorowski JC, Wagner B.Lyme arthritis, a well-documented subtype of arthritis in humans and dogs, is caused by Borrelia burgdorferi and spread primarily through ticks (Ixodes spp.). While Lyme disease in horses is known to cause a variety of clinical signs, its involvement in the development of equine arthritis is controversial. As climate change enables tick populations to expand, more horses could be exposed to B. burgdorferi; therefore, a greater understanding of how Lyme disease affects joints is critical to preserving soundness. Objective: To determine if systemic, naturally occurring Lyme disease had a discern...
Da Silva-Álvarez E, Martín-Cano FE, Alonso JM, Becerro-Rey L, Zabalo-Palomo C, Gil MC, Peña FJ, Ortega-Ferrusola C.This study aims to characterize and compare the uterine fluid proteome and cytokine profile of reproductively healthy mares (HM; n = 15) and mares with Streptococcus equi subsp. zooepidemicus (S. zooepidemicus)-associated endometritis (SAE; n = 9). Uterine flush samples collected during the follicular phase were analyzed by shotgun proteomics and multiplex cytokine assays. Equine proteins were mapped to human orthologs, and enrichment and network analyses were performed using g:Profiler, Metascape, ToppGene, and STRING/MCODE. SAE mares showed higher levels of IL-1α, IL-1β, GRO, IL12p...
Sadowska A, Molcan T, Słyszewska M, Skarzynski DJ, Ferreira-Dias G, Szóstek-Mioduchowska A.Equine endometrosis is a chronic degenerative condition of the endometrium. A hallmark feature of endometrosis is endometrial fibrosis accompanied by degenerative changes in the adjacent tissue structure. Tumor necrosis factor α (TNFα), a pleiotropic cytokine produced by various immune cells, plays a dual role in coordinating immune responses and regulating cell/tissue homeostasis, making it an important regulator of fibrotic-related disorders. However, the exact role of TNFα in the development of equine endometrial fibrosis remains to be discovered and explained. Therefore, the main aim of...
Gröndahl G, Righetti F, Aspán A, Bjerketorp J, Frosth S, Frykberg L, Jacobsson K, Guss B, Paillot R, Flock JI, Henriques-Normark B, Waller AS.Strangles, caused by Streptococcus equi subspecies equi (S. equi), is a prevalent infectious disease of horses. This is the first report on the use of a new vaccine, Strangvac, in a natural outbreak of strangles. Objective: To measure the effects of Strangvac vaccination during an outbreak of strangles at a Swedish farm. Methods: Longitudinal cohort study. Methods: Healthy horses (n = 17) were vaccinated on day 0, which occurred 23 days after strangles was first confirmed in three unvaccinated horses on the same farm. Blood serum samples were collected on day 0, day 28 and day 489. A com...
van Heule M, Verstraete M, Norris JK, Graniczkowsa KB, Scoggin KE, Ali HE, Ball BA, De Spiegelaere W, Daels P, Weimer BC, Dini P.Nocardioform placentitis (NP) is an understudied form of equine placentitis historically attributed to nocardioform bacteria, yet it remains uncertain whether these organisms are the sole pathogens involved. Objective: To elucidate the pathophysiology of NP and the host-pathogen interaction. Methods: In vivo clinical multi-omics study. Methods: Dual RNA sequencing was performed to profile transcriptionally active microbial communities and concurrent placental transcriptome responses in samples from 31 placentas with and without NP. Untargeted metabolomics was performed to study the associated ...
Mitlyng N, Hobbs KJ, Cooper BL, Sheats MK.Lipopolysaccharide (LPS) is frequently used in equine research to model clinical endotoxemia; however, there is no standardized protocol for inducing cytokine production in equine whole blood. To address this knowledge gap, the goal of this study was to compare the cytokine responses elicited by three different LPS stimulation protocols. Whole blood was collected from six healthy horses (aged 5-30 years; mixed breeds and genders) from the North Carolina State University teaching herd (IACUC #23-412). Sixty milliliters of heparinized blood were aseptically drawn and divided into 15 mL aliquots....
Meng C, Wang J, Zeng Y, Yao X, Meng J.This study investigated the effects of varying proline supplementation doses in weaned foals. Twenty-eight weaned foals (approximately 5 months of age; body weight: 54.45 ± 11.33 kg; with an equal number of males and females) were randomly assigned to one of four groups-a control group, a low-dose group (20 mg/kg·d), a medium-dose group (40 mg/kg·d), and a high-dose group (60 mg/kg·d)- receiving continuous supplementation for 60 days. Blood samples were collected periodically for the analysis of hormones, antioxidants, immune parameters, and plasma amino acids. Concurrently, fecal 16S rRNA...
George JM, Leatherwood JL, Paris BL, Arnold CE, Glass KG, Conrad MB, Martinez RE, Vergara-Hernandez FB, Nielsen BD, Colbath AC, Welsh TH, Bradbery AN.Perceived chondroprotective and anti-inflammatory benefits of bisphosphonates in the juvenile horse has led to extra-label use without supportive data regarding intra-articular effects on cartilage metabolism and inflammation. Thirty-two yearling Quarter Horses were stratified into 4 treatment groups by age (500 ± 13 d), BW (336 ± 26 kg), sex (n = 16 female; n = 16 male) and initial bone optical density for a 140-d study. The study consisted of two exercise phases: Phase 1 (d 0-84) emulated sales preparation and Phase 2 (d 99-140) mimicked early exercise training. Horses we...
Beaumont RE, Flood C, Guest DJ.Interleukin 1 beta (IL-1β) is upregulated following a tendon injury and in vitro studies have shown that it leads to numerous negative effects on tendon cell function and gene expression. IL-1β activates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and we hypothesised that inhibiting NF-κB activation would mediate the negative effects of IL-1β on equine tendon cells in 3-dimensional (3D) cultures. Results: Here, we tested three inhibitors of NF-κB signalling (Bortezomib, BAY11-7082 and Wedelolactone) along withTJ-M2010-5, an inhibitor of MyD88, which is a critic...
The aim of the study was to identify proteomic signatures from the serum of horses affected by simple obstructive intestinal colic to characterize the pathological process and to assess potential biomarkers for early diagnosis. Seven horses with obstructive colic received venous blood samples for determination of standard hematobiochemical, inflammatory, and lipid profiles at the time of initial clinical examination and after conservative therapy upon recovery. Proteomic profiling was also performed on all samples by means of a within-group analysis (sick horses at discharge vs. sick horses at...
Piecuch A, Szterk A.This review highlights the role of β-glucans-specifically β(1 → 3), β(1 → 6), and β(1 → 4)-glucans-as water-soluble dietary fibres in animal nutrition and health. Sourced from yeast, plants, seaweed, and mushrooms, β-glucans differ in structure depending on origin, which affects their solubility and biological activity. Recent studies emphasize their therapeutic potential in horses, particularly for managing gastric ulcers, viral infections, immune dysfunction, and poor performance. The review summarizes data on effective dosages, formulations, and sources of β-glucans tailor...
Feijo LS, Ledeck J, Wolfsdorf K, Ponthier J, Parry S, Felippe MJB.Associations between the immune and endocrine systems during equine pregnancy remain poorly understood. Based on the hypothesis that distinct phases of the equine healthy gestation are characterized by specific associations between circulating immunological and hormonal parameters, contributing to pregnancy maintenance, this investigation aimed to: (i) evaluate how circulating immunological and hormonal parameters change across different phases of pregnancy; (ii) investigate associations between changes in circulating immunological and hormonal parameters; and (iii) propose potential hormonal ...
Salinas-Varas C, Espinosa G, Muñoz-Caro T, Conejeros I, Gärtner U, Fey K, Arnhold S, Taubert A, Hermosilla C.Neutrophil extracellular trap (NET) are thin and long web-like structures composed of DNA and antimicrobial proteins released by activated polymorphonuclear neutrophils (PMN) as part of the innate immune response. Adipose-derived stem cells (ADSCs) represent an accessible, abundant and minimal invasive source of mesenchymal stem cells (MSCs), with high regenerative potential, immunomodulatory and anti-inflammatory properties. Although recognized immunomodulatory properties of ADSCs, their interaction with PMN and their role on NET formation remains poorly characterized. The present study aimed...
Linde P, Kurihara J, Chow L, Williams ZJ, Hendrickson D, Bass L, Dow S, Pezzanite LM.Innate immune responses within the joint are now known to play a key role in osteoarthritis (OA) pathogenesis. However, comparatively little is known regarding the role of adaptive immune responses in OA, and whether they may be important for initiating and sustaining progressive low-level joint inflammation. Therefore, we evaluated spontaneous osteoarthritis in horses to investigate whether antibodies recognizing live joint cells (chondrocytes, synoviocytes) were present in blood or synovial fluid, and to identify possible cellular target antigens. We found that horses with advanced OA had an...
Lewis NS, Daly JM, Russell CA, Horton DL, Skepner E, Bryant NA, Burke DF, Rash AS, Wood JL, Chambers TM, Fouchier RA, Mumford JA, Elton DM, Smith DJ.Equine influenza virus is a major respiratory pathogen in horses, and outbreaks of disease often lead to substantial disruption to and economic losses for equestrian industries. The hemagglutinin (HA) protein is of key importance in the control of equine influenza because HA is the primary target of the protective immune response and the main component of currently licensed influenza vaccines. However, the influenza virus HA protein changes over time, a process called antigenic drift, and vaccine strains must be updated to remain effective. Antigenic drift is assessed primarily by the hemagglu...
Guest DJ, Smith MR, Allen WR.Autologous mesenchymal progenitor cells (MPCs) purified from bone marrow aspirates are being used in the treatment of superficial digital flexor tendon (SDFT) injuries in the horse with promising results. In this study the fate of autologous and allogeneic MPCs following injection into the SDFT was monitored by stable transfection of MPCs with green fluorescent protein (GFP). Small lesions were created manually in one forelimb SDFT of 2 horses and injected with autologous MPCs, allogeneic MPCs or bone marrow supernatant alone. Post mortem examinations performed after 10 or 34 days revealed GFP...
Bowen RA, Nemeth NM.West Nile virus emerged recently in North America as a serious human and animal pathogen. This review summarizes the use of experimental infections with West Nile virus in diverse vertebrate species that have been used to answer fundamental questions about the host response, pathogenesis of West Nile virus infection and virus evolution. Results: West Nile virus has an extremely broad vertebrate host range. Infection of common species of birds has defined those with high vs. low potential to serve as amplifying hosts for the virus. In general, mammals (primates, horses, companion animals) are d...
Vargas A, Boivin R, Cano P, Murcia Y, Bazin I, Lavoie JP.Severe neutrophilic asthma is poorly responsive to glucocorticosteroids (GC). Neutrophil extracellular traps (NETs) within the lungs have been associated with the severity of airway obstruction and inflammation in asthma, and were found to be unaffected by GC in vitro. As IL-17 is overexpressed in neutrophilic asthma and contributes to steroid insensitivity in different cell types, we hypothesized that NETs formation in asthmatic airways would be resistant to GC through an IL-17 mediated pathway. Six neutrophilic severe asthmatic horses and six healthy controls were studied while being treated...
Marsh GA, Wang LF.Henipavirus, including Hendra and Nipah viruses, is a group of emerging bat-borne paramyxoviruses which were responsible for severe disease outbreaks in humans, horses and pigs. The mortality rate of human infection varies between 50 and 100%, making them one of the most deadly viruses known to infect humans. Its use of highly conserved cell surface molecules (ephrin) as entry receptors and its highly effective replication and fusion strategies are believed to be important characteristics responsible for its high pathogenicity. Henipavirus also encodes multiple accessory proteins which play a ...
Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL.Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proli...
Scheel TK, Kapoor A, Nishiuchi E, Brock KV, Yu Y, Andrus L, Gu M, Renshaw RW, Dubovi EJ, McDonough SP, Van de Walle GR, Lipkin WI, Divers TJ....Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼ 3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3'-UTR was determined and consists...
Katila T.This review attempts to summarize the current knowledge on uterine inflammatory response after mating in horses, pigs and cattle. Post-mating endometritis has been extensively studied in horses as it has been considered to cause infertility. The inflammation is known to occur also in cattle, but it has not been investigated to a similar extent. There are a number of publications about mechanisms of post-mating uterine inflammation in pigs, which seem to resemble those in horses. The major focus of this review is the horse, but relevant literature is presented also on swine and cattle. Spermato...
Grieder FB, Vogel SN.To investigate the role of type I interferon (IFN) and its regulatory transacting proteins, interferon regulatory factors (IRF-1 and IRF-2), in early protection against infection with virulent Venezuelan equine encephalitis virus (VEE), we utilized mice with targeted mutations in the IFN-alpha/beta receptor, IRF-1, or IRF-2 genes. IFN-alpha/beta-receptor knockout mice are highly susceptible to peripheral infection with virulent or attenuated VEE, resulting in their death within 24 and 48 h, respectively. Treatment of normal macrophages with anti-IFN-alpha/beta antibody prior to and during infe...
Ramsay JD, Evanoff R, Wilkinson TE, Divers TJ, Knowles DP, Mealey RH.Equine hepacivirus (EHCV; nonprimate hepacivirus) is a hepatotropic member of the Flaviviridae family that infects horses. Although EHCV is the closest known relative to hepatitis C virus (HCV), its complete replication kinetics in vivo have not been described, and direct evidence that it causes hepatitis has been lacking. In this study, we detected EHCV in 2 horses that developed post-transfusion hepatitis. Plasma and serum from these horses were used to experimentally transmit EHCV to 4 young adult Arabian horses, two 1-month-old foals (1 Arabian and 1 Arabian-pony cross), and 2 foals (1 Ara...
Carrade DD, Affolter VK, Outerbridge CA, Watson JL, Galuppo LD, Buerchler S, Kumar V, Walker NJ, Borjesson DL.BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the sam...
Stewart AS, Pratt-Phillips S, Gonzalez LM.All species, including horses, suffer from alterations that increase intestinal permeability. These alterations, also known as "leaky gut," may lead to severe disease as the normal intestinal barrier becomes compromised and can no longer protect against harmful luminal contents including microbial toxins and pathogens. Leaky gut results from a variety of conditions including physical stressors, decreased blood flow to the intestine, inflammatory disease, and pathogenic infections, among others. Several testing methods exist to diagnose these alterations in both a clinical and research setting....
Nara PL, Garrity RR, Goudsmit J.The production of immunoglobulin capable of neutralizing the infectivity of a virus represents one of the most remarkable molecular accomplishments of the host's available immune defenses. It should be no surprise that a virus that has existed in the parenchyma of the immune system has evolved as an equally dynamic molecule (i.e., viral envelope) for survival. Neutralizing immunoglobulin (Ig) can best serve the host under conditions where the invading pathogen requires a well-defined cell-free state for establishing an infection or transmission. Evidence for a controlling and therefore protect...
Edington N, Bridges CG, Patel JR.Eight mares were infected with equid herpesvirus-1 subtype 1 isolated from a case of equine paresis. In two mares killed at 4 d.p.i. immunofluorescence showed endothelial cell infection together with thrombosis in the rete arteriosus of the nasal mucosa and also in the spinal cord of one of these mares. Circulating platelet counts in the other six mares fell as early as 2 d.p.i. and remained depressed for seven days. Circulating immune complexes started to appear at 2 d.p.i., reached maximum levels at 10 d.p.i., but were undetectable at 28 d.p.i. Three of the six remaining mares developed vary...
Berglund AK, Schnabel LV.Allogeneic mesenchymal stem cells (MSCs) are a promising cell source for treating musculoskeletal injuries in horses. Controversy exists, however, over whether major histocompatibility complex (MHC)-mismatched MSCs are recognised by the recipient immune system and targeted for death by a cytotoxic antibody response. Objective: To determine if cytotoxic anti-MHC antibodies generated in vivo following MHC-mismatched MSC injections are capable of initiating complement-dependent cytotoxicity of MSCs. Methods: Experimental controlled study. Methods: Antisera previously collected at Days 0, 7, 14 an...
Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL.Mesenchymal stem cells have demonstrated immunomodulatory capabilities as well as modest efficacy in animal models of joint injury, warranting further study as a potential treatment of joint disease. The goal of the study was to investigate the blood and synovial immune and histologic response to intra-articular injection of autologous, allogeneic, and xenogeneic bone marrow-derived mesenchymal stem cells (MSC) in horses. The study group consisted of 6 five-year-old Thoroughbred mares that had been injected previously with 15 million, genetically modified autologous, allogeneic, or xenogeneic ...
Jacobsen S, Kjelgaard-Hansen M, Hagbard Petersen H, Jensen AL.The aim of the present study was to evaluate whether equine serum amyloid A (SAA) concentrations could be measured reliably with a turbidometric immunoassay (TIA) developed for use with human serum. Intra- and inter-assay imprecision were evaluated by multiple measurements on equine serum pools. Assay inaccuracy was determined by linearity under dilution. The assay was subsequently used for measuring SAA concentrations in clinically healthy horses, horses with inflammatory diseases, horses with non-inflammatory diseases, and in horses before and after castration. In pools with low, intermediat...
Leclere M, Lavoie-Lamoureux A, Joubert P, Relave F, Setlakwe EL, Beauchamp G, Couture C, Martin JG, Lavoie JP.Recent studies suggest that airway smooth muscle remodeling is an early event in the course of asthma. Little is known of the effects of long-term antigen avoidance and inhaled corticosteroids on chronically established airway remodeling. We sought to measure the effects of inhaled corticosteroids and antigen avoidance on airway remodeling in the peripheral airways of horses with heaves, a naturally occurring asthma-like disease. Heaves-affected adult horses with ongoing airway inflammation and bronchoconstriction were treated with fluticasone propionate (with and without concurrent antigen av...
Ma G, Azab W, Osterrieder N.The equine herpesviruses type 1 (EHV-1) and 4 (EHV-4) are ubiquitous pathogens that affect horse populations on all continents. Despite widespread vaccination, EHV-1 and EHV-4 infections remain a permanent risk. While the two viruses share a high degree of genetic and antigenic similarity, they differ significantly in host range and pathogenicity. Compared to EHV-4, which mainly infects horses and causes respiratory disease, EHV-1 has a broader host range and can result in respiratory disease, abortions, neonatal death, and equine herpesvirusmyeloencephalopathy (EHM). Recent studies have eluci...
Meijer WG, Prescott JF.Rhodococcus equi is an important cause of subacute or chronic abscessating bronchopneumonia of foals up to 3-5 months of age. It shares the lipid-rich cell wall envelope characteristic of the mycolata, including Mycobacterium tuberculosis, as well as the ability of pathogenic members of this group to survive within macrophages. The possession of a large virulence plasmid in isolates recovered from pneumonic foals is crucial for virulence. The plasmid contains an 27 kb pathogenicity island (PI) that encodes seven related virulence-associated proteins (Vaps), including the immunodominant surface...
Giguère S, Prescott JF.Since the 1986 Rhodococcus equi workshop, there have been major breakthroughs in understanding the epidemiology of, the virulence of, and the immune response to, this intriguing pathogen. However, with the exception of the use of hyperimmune plasma for the prevention of the disease (Martens et al., 1989; Madigan et al., 1991) the clinical aspects of R. equi infections have essentially remained unchanged. This article reviews the various clinical manifestations and summarizes recent advances in diagnosis, treatment and prevention of R. equi infections in foals.
El Garch H, Minke JM, Rehder J, Richard S, Edlund Toulemonde C, Dinic S, Andreoni C, Audonnet JC, Nordgren R, Juillard V.Successful vaccination against West Nile virus (WNV) requires induction of both neutralizing antibodies and cell-mediated immune responses. In this study, we have assessed the ability of a recombinant ALVAC-WNV vaccine (RECOMBITEK WNV) to elicit neutralizing antibodies and virus-specific cell-mediated immune responses in horses. In addition, we examined whether prior exposure to ALVAC-WNV vaccine would inhibit B and cell-mediated immune responses against the transgene product upon subsequent booster immunizations with the same vaccine. The results demonstrated that the recombinant ALVAC-WNV va...
H A Morris L, M McCue P, Aurich C.Endometritis in the mare begins as a normal physiological inflammatory response to breeding that involves both a mechanical and immunological response pathway activated to rid the uterus of semen and bacteria. With successful resolution of this inflammation, the mare's uterus will provide a hospitable environment for the development of the semi-allogenic conceptus. If the mare fails to resolve this inflammatory response within 48 h of breeding, she will become susceptible to persistent breeding-induced endometritis (PBIE) which will have detrimental effects on her fertility. This condition can...
Perryman LE, O'Rourke KI, McGuire TC.Six normal and four immunodeficient horses were injected with a cloned variant of equine infectious anemia virus (EIAV). The six normal horses had detectable EIAV in their plasma by 7 days postinjection. During their primary viremic episode, which was accompanied by fever and anemia, maximum titers of EIAV in plasma ranged from 10(3.8) to 10(4.8) 50% tissue culture infective doses per ml. All six normal horses cleared detectable virus from their plasma by 21 to 35 days after injection. Horses with combined immunodeficiency became viremic by 9 days postinjection and also developed anemia. In co...
Hondalus MK.Inhalation of the soil-borne organism, Rhodococcus equi, can lead to a chronic and severe pyogranulomatous pneumonia in young horses and immunocompromised people. In addition, ulcerative colitis is a common sequela to infection in foals, and dissemination from the lung to other body sites is not uncommon in either the horse or man. Although the facultative intracellular bacterium is susceptible to neutrophil-mediated killing, it is able to resist innate macrophage defenses and establish residence within the intracellular environment of that phagocyte. Definitive virulence factors of R. equi ha...
Afable MG, Shaik M, Sugimoto Y, Elson P, Clemente M, Makishima H, Sekeres MA, Lichtin A, Advani A, Kalaycio M, Tiu RV, O'Keefe CL, Maciejewski JP.A combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia. Methods: Twenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin. Results: Response rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte glob...
Muscatello G, Leadon DP, Klayt M, Ocampo-Sosa A, Lewis DA, Fogarty U, Buckley T, Gilkerson JR, Meijer WG, Vazquez-Boland JA.Infection with Rhodococcus (Corynebacterium) equi is a well-recognised condition in foals that represents a consistent and serious risk worldwide. The condition manifests itself primarily as one of pulmonary abscessation and bronchitis, hence the terminology of 'rattles' derived from its most obvious clinical sign, frequently terminal when first identified. This review addresses the clinical manifestation, bacteriology and pathogenesis of the condition together with recent developments providing knowledge of the organism in terms of virulence, epidemiology, transmission and immune responses. E...
Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA.Heaves in horses shares many similarities with human asthma, including lower airway inflammation, reversible airway obstruction, and bronchial hyperresponsiveness. Extrinsic asthma is an allergic response to environmental allergens and a similar immunologic mechanism may be implicated in heaves. It is now recognized that a Th2 subset of CD4+ lymphocytes is associated with allergic diseases such as atopic asthma. The purpose of this study was to determine whether airway inflammation in heaves is associated with a pattern of expression of cytokine suggestive of a Th2 type response. The expressio...
Lewis MJ, Wagner B, Woof JM.Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1>IgG3>IgG4>IgG7>IgG2=IgG5>IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately t...
Goodman LB, Wagner B, Flaminio MJ, Sussman KH, Metzger SM, Holland R, Osterrieder N.Equine herpesvirus type 1 (EHV-1) is a ubiquitous alphaherpesvirus of horses which causes rhinopneumonitis, abortion and myeloencephalopathy. To test the efficacy of commercial vaccines in protection against neurological EHV-1 challenge, groups of five horses were immunized with modified-live virus or an inactivated vaccine, or received placebo. Horses were challenged by aerosol with a recent virus isolate obtained from a case of paralytic EHV-1. The duration of fever decreased significantly in the modified-live virus vaccine group. Three animals in each of the inactivate and control groups sh...
