The equine immune system is a complex network of cells, tissues, and organs that work collaboratively to defend against pathogens and maintain homeostasis. It consists of innate and adaptive components, each with distinct functions and mechanisms. The innate immune system provides the first line of defense through physical barriers, phagocytic cells, and the complement system. The adaptive immune system involves lymphocytes, such as B cells and T cells, which generate specific responses to antigens and provide immunological memory. Research in equine immunology explores the interactions between these components, the impact of genetic and environmental factors on immune function, and the development of vaccines and therapeutics. This page gathers peer-reviewed studies and scholarly articles focusing on the mechanisms, regulation, and clinical applications of the equine immune system in health and disease.
Harman RM, Rajesh A, Van de Walle GR.Treatment of skin wounds is a high priority in veterinary medicine because healthy uncompromised skin is essential for the well-being of horses. Stem cells and other biologic therapies offer benefits by reducing the need for surgical procedures and conventional antibiotics. Evidence from in vitro studies and small in vivo trials supports the use of equine stem cells and biologics for the treatment of acute and chronic cutaneous wounds. Larger clinical trials are warranted to better evaluate the regenerative and immunological responses to these treatments. Additionally, delivery methods and t...
Vasoya D, Tzelos T, Benedictus L, Karagianni AE, Pirie S, Marr C, Oddsdóttir C, Fintl C, Connelley T.The Major Histocompatibility Complex (MHC) genes play a key role in a number of biological processes, most notably in immunological responses. The MHCI and MHCII genes incorporate a complex set of highly polymorphic and polygenic series of genes, which, due to the technical limitations of previously available technologies, have only been partially characterized in non-model but economically important species such as the horse. The advent of high-throughput sequencing platforms has provided new opportunities to develop methods to generate high-resolution sequencing data on a large scale and app...
Li L, Maboni G, Lack A, Gomez DE.Nontuberculous mycobacteria (NTM) infections are increasing in human and veterinary medicine. Although horses were initially thought to be resistant to NTM infection, reports of horses suffering from gastrointestinal, respiratory, and reproductive diseases associated with NTM have increased in the last few decades. The aim of this literature review is to summarize the mycobacteria species found in horses, describe clinical manifestations, diagnostic and treatment approaches, and public health concerns of NTM infection in horses. Clinical manifestations of NTM in horses include pulmonary diseas...
Pimenta J, Pires I, Prada J, Cotovio M.Melanocytic tumors are an important neoplastic disease in human and veterinary medicine, presenting large differences regarding tumor behavior between species. In horses, these tumors present a prolonged benign behavior, with rare invasiveness and metastases. In humans and small animals, invasion and metastasis have been associated with an Epithelial-Mesenchymal Transition, where the loss of E-cadherin expression plays a key role in tumor progression. This process and the role of E-cadherin have not yet been evaluated in equine melanocytic tumors. This study aimed to assess the immunolabeling ...
Wang XF, Zhang X, Ma W, Li J, Wang X.Equine infectious anemia virus (EIAV) is a member of the lentivirus genus in the Retroviridae family and is considered an animal model for HIV/AIDS research. An attenuated EIAV vaccine, which was successfully developed in the 1970s by classical serial passage techniques, is the first and only lentivirus vaccine that has been widely used to date. Restriction factors are cellular proteins that provide an early line of defense against viral replication and spread by interfering with various critical steps in the viral replication cycle. However, viruses have evolved specific mechanisms to overcom...
Wong KS, Cheung HW, Choi YC, To NS, Wan TSM, Ho ENM.Recombinant human follistatin (rhFST) is a potential performance-enhancing agent owing to its stimulating effect on muscle growth. Administration of rhFST to athletes is prohibited in human sports by the World Anti-Doping Agency (WADA) and in horseracing according to Article 6 of the International Agreement on Breeding, Racing and Wagering published by the International Federation of Horseracing Authorities (IFHA). For effective control of the potential misuse of rhFST in flat racing, methods for screening and confirmatory analysis are required. This paper describes the development and validat...
Kašpárková N, Bártová E, Žákovská A, Budíková M, Sedlák K.Lyme disease, caused by some strains of bacterial spirochetes Borrelia burgdorferi sensu lato (Bbsl), affects humans but also domestic animals including horses. The primary pathogens in horses in Europe are B. afzelii, B. garinii and B. burgdorferi sensu stricto. To our knowledge, there are no data available on the seropositivity of B. burgdorferi s.l. in horses from the Czech Republic. In this country, horses are mainly used for sport, breeding, and recreational riding in areas where vectors of B. burgdorferi s.l. are present, which is why they are frequently at risk of infection. The aim of ...
Hemberg E, Niazi A, Guo Y, Debnár VJ, Vincze B, Morrell JM, Kútvölgyi G.The presence of a microbiome/microbiota in the placenta is hotly debated. In previous studies, the presence of bacteria in equine amniotic fluid and umbilical blood was independent of foal health. The objective of the present study was to determine if the same bacteria are present in the equine placenta as in amniotic fluid and umbilical blood. Samples were obtained from 24 parturient mares and foals. Placental bacterial DNA was extracted, and the microbiome was identified using 16S rRNA sequencing. All amniotic fluid samples contained some polymorphonucleocytes; bacteria were isolated from fo...
Gehlen H, Inerle K, Bartel A, Stöckle SD, Ulrich S, Briese B, Straubinger RK.There are limited data on Lyme borreliosis (LB), a tick-borne disease caused by the Borrelia burgdorferi sensu lato complex, in horses. Seropositivity is not necessarily associated with clinical disease. Data on seropositivity against Borrelia burgdorferi and Anaplasma phagocytophilum in German horses are sparse. Therefore, serum samples from horses (n = 123) suspected of having Lyme borreliosis and clinically healthy horses (n = 113) from the same stables were tested for specific antibodies against Borrelia burgdorferi sensu lato and Anaplasma phagocytophilum. The samples were screened for an...
Beaumont RE, Smith EJ, Zhou L, Marr N, Thorpe CT, Guest DJ.We investigated how Interleukin 1 beta (IL-1β) impacts equine tenocyte function and global gene expression in vitro and determined if these effects could be rescued by pharmacologically inhibiting nuclear factor-κB (NF-B) or interleukin 1 signalling. Equine superficial digital flexor tenocytes were cultured in three-dimensional (3D) collagen gels and stimulated with IL-1β for two-weeks, with gel contraction and interleukin 6 (IL6) measured throughout and transcriptomic analysis performed at day 14. The impact of three NF-B inhibitors on gel contraction and IL6 secretion were measured in 3D ...
Yates KM, Stilwell NK, Fontenot RL, Betbeze CM.To determine the in vitro antibacterial efficacy of equine and canine autologous conditioned plasma (ACP) and amniotic membrane extract eye drops (AMEED) against aerobic bacteria common to the corneal surface. Methods: Canine (n = 4) and equine (n = 4) anticoagulated whole blood samples were sterilely collected, pooled for each species, and processed using the Arthrex ACP® Double-Syringe System. Platelet counts were performed on ACP and pooled blood. AMEED were obtained from a commercial source. An electronic medical records search (2013-2022) identified aerobic bacteria cultured from...
Kakoi H, Kikuchi M, Ishige T, Hirosawa Y, Tanaka S, Nagata SI.To confirm the positive conversion of antibodies against erythrocyte antigens in horses, possible blood transfusion donor horses selected from draft horse populations were periodically monitored with an indirect antiglobulin (Coombs) test for approximately 3 years. In this study, 19 horses (16 females and 3 males) were investigated, and five mares showed alloantibodies during the monitoring period. Four mares were typically pregnant when positive conversion was detected, whereas no particular cause of conversion could be observed for one mare based on its clinical records. In the analyzed hors...
Lee DH, Lee EB, Seo JP, Ko EJ.Toll-like receptor (TLR) agonists have been used as adjuvants to modulate immune responses in both animals and humans. Objective: The objective of this study was to evaluate the combined effects of the TLR 4 agonist monophosphoryl lipid A (MPL) and the TLR 3 agonist polyinosinic:polycytidylic acid (Poly I:C) on equine peripheral blood mononuclear cells (PBMCs), monocyte-derived dendritic cells (MoDCs), and bone marrow-derived mesenchymal stromal cells (BM-MSCs). Methods: The PBMCs, MoDCs, and BM-MSCs collected from three mixed breed horses were treated with MPL, Poly I:C, and their combination...
Kinoshita Y, Yamanaka T, Kodaira K, Niwa H, Uchida-Fujii E, Ueno T.A two-dose revaccination against tetanus is recommended for horses over 2 years old in Japan with no history of vaccination in the previous year. Here, the need for two-dose revaccination was evaluated in terms of antibody titers for each vaccine type, namely monovalent or multivalent. There was no difference in antibody titers between one- and two-dose regimens for up to 1 year, except at 8 weeks with the multivalent vaccine, and all horses had sufficient antibody titers for 1 year of tetanus prophylaxis. These results suggest that one-dose revaccination, regardless of the vaccine type, is as...
Hayes AM, Kastl B, Perry E, Moore AR, Springer NL.Myeloma-related disorders, including multiple myeloma, extramedullary plasmacytoma, and solid osseous plasmacytoma, are rare in horses. Clinical complaints for myeloma-related disorders are nonspecific, and when present, M-protein location is more variable on protein electrophoresis in horses relative to dogs and cats. Here, we describe a case of a 15-year-old Thoroughbred mare who presented with recurrent blepharitis. Marked hyperglobulinemia was an incidental finding on routine hematologic and biochemical testing. Bone marrow aspiration consisted of >30% plasma cells, and serum protein el...
Li Z, He Y, Ge L, Quan R, Chen J, Hu Y, Sa R, Liu J, Ran D, Fu Q, Shi H.Equine herpesvirus type 1 (EHV-1) poses a global threat to equines. The anticancer agent berbamine (BBM), a bioactive alkaloid, has been shown to inhibit viral infection. However, whether BBM can inhibit EHV-1 infection remains unclear. This study investigated the effect of BBM treatment on EHV-1 infection. Quantitative PCR (qPCR), immunoblotting, the Reed-Muench method, and pathological examination were employed to study the ability of BBM to inhibit EHV-1 infection, viral DNA replication, viral protein production, virion secretion, and cytopathogenesis in vitro and in vivo. The in vitro stud...
Schwarz ER, Long MT.West Nile virus (WNV) neuroinvasive disease threatens the health and well-being of horses and humans worldwide. Disease in horses and humans is remarkably similar. The occurrence of WNV disease in these mammalian hosts has geographic overlap with shared macroscale and microscale drivers of risk. Importantly, intrahost virus dynamics, the evolution of the antibody response, and clinicopathology are similar. The goal of this review is to provide a comparison of WNV infection in humans and horses and to identify similarities that can be exploited to enhance surveillance methods for the early dete...
Punzón E, García-Castillo M, Rico MA, Padilla L, Pradera A.Mesenchymal stem cells are multipotent cells with a wide range of therapeutic applications, including, among others, tissue regeneration. This work aims to test the safety (EUC-MSC) of intra-articular administration of equine umbilical cord mesenchymal stem cells in young healthy dogs under field conditions following single and repeated administration. This was compared with the safety profile of allogenic canine adipose derived mesenchymal stem cells (CAD-MSC) and placebo in order to define the safety of xenogeneic use of mesenchymal stem cells when administered intra-articular. Twenty-four p...
Anderson C, Baha H, Boghdeh N, Barrera M, Alem F, Narayanan A.Zoonotic pathogens that are vector-transmitted have and continue to contribute to several emerging infections globally. In recent years, spillover events of such zoonotic pathogens have increased in frequency as a result of direct contact with livestock, wildlife, and urbanization, forcing animals from their natural habitats. Equines serve as reservoir hosts for vector-transmitted zoonotic viruses that are also capable of infecting humans and causing disease. From a One Health perspective, equine viruses, therefore, pose major concerns for periodic outbreaks globally. Several equine viruses ha...
Marsella R, White S, Fadok VA, Wilson D, Mueller R, Outerbridge C, Rosenkrantz W.Allergic skin diseases are common in horses worldwide. The most common causes are insect bites and environmental allergens. Objective: To review the current literature and provide consensus on pathogenesis, diagnosis, treatment and prevention. Methods: The authors reviewed the literature up to November 2022. Results were presented at North America Veterinary Dermatology Forum (2021) and European Veterinary Dermatology Congress (2021). The report was available to member organisations of the World Association for Veterinary Dermatology for feedback. Conclusions: Insect bite hypersensitivity (IBH...
Terhaar HM, Henriksen ML, Mehaffy C, Hess A, McMullen RJ.The objective of this study was to use shotgun label-free tandem mass spectrometry (LF-MS/MS) to evaluate aqueous humor (AH) from horses with uveitis (UH) compared to ophthalmologically healthy horses (HH). Methods: Twelve horses diagnosed with uveitis based on ophthalmic examination and six ophthalmologically healthy horses (postmortem) purchased for teaching purposes. Methods: All horses received a complete ophthalmic examination and physical exam. Aqueous paracentesis was performed on all horses and AH total protein concentrations were measured with nanodrop (TPn) and refractometry (TPr). A...
Hassall L, Rigsby P, Stickings P.The International Standard for Diphtheria Antitoxin Equine is essential for the standardisation of assays used to determine the potency of therapeutic diphtheria antitoxin products produced from equine serum. This paper describes the production and characterization of the 2nd International Standard for Diphtheria Antitoxin Equine and its calibration in International Units. Calibration was performed by toxin neutralization test in vivo and in vitro (Vero cell assay), and potency was expressed relative to the 1st International Standard to ensure continuity of the International Unit. The candidat...
Bannai H, Kambayashi Y, Nemoto M, Yamanaka T, Tsujimura K.Using 85 sera collected from horses that had been experimentally infected with equine infectious anemia virus (EIAV) and 200 field sera collected from racehorses in Japan, we compared 4 agar gel immunodiffusion (AGID) kits for serologic detection of EIAV antibodies from Idexx, VMRD, IDvet, and the National Engineering Research Center of Veterinary Biologics, China (NECVB). The positive control lines were sufficiently clear in all kits for evaluation to be made, with slight differences in sharpness: NECVB was the sharpest, followed by VMRD, IDvet, and Idexx. The test results for all 285 samples...
Craig NM, Munguia NS, Trujillo AD, Wilkes R, Dorr M, Marsella R.Preliminary evidence supports a role for IL-31 in equine insect bite hypersensitivity (IBH) and pruritus. Our studies investigated IL-31 and IL-31 receptor-α (IL-31RA) transcription in leukocytes from normal and IBH horses in response to Culicoides nubeculosus. 19 normal and 15 IBH horses were recruited in the summer of 2019 (low-dose study) and 8 normal and 10 IBH horses in the winter of 2022 to 2023 (high-dose study). Normal horses had no history or signs of allergic skin disease, while IBH horses had a history and clinical signs compatible with IBH. Pruritus was scored using a visual analo...
Fan Y, Lou J, Tam CC, Wen W, Conrad F, Leal da Silva Alves P, Cheng LW, Garcia-Rodriguez C, Farr-Jones S, Marks JD.Equine-derived antitoxin (BAT) is the only treatment for botulism from botulinum neurotoxin serotype G (BoNT/G). BAT is a foreign protein with potentially severe adverse effects and is not renewable. To develop a safe, more potent, and renewable antitoxin, humanized monoclonal antibodies (mAbs) were generated. Yeast displayed single chain Fv (scFv) libraries were prepared from mice immunized with BoNT/G and BoNT/G domains and screened with BoNT/G using fluorescence-activated cell sorting (FACS). Fourteen scFv-binding BoNT/G were isolated with K values ranging from 3.86 nM to 103 nM (median K 2...
Smith HL, Berglund AK, Robertson JB, Schnabel LV, McMullen RJ, Gilger BC, Oh A.The objective of the study was to determine the effect of gentamicin on CD3+ T-lymphocyte proliferation and cell viability using an in vitro cell culture model as a means of investigating the mechanism of action of low-dose intravitreal gentamicin injection. Methods: Three adult horses with no evidence of ophthalmic or systemic disease. Methods: Peripheral blood lymphocytes were treated with gentamicin at concentrations 37.5 μg/mL, 112.5 μg/mL, 187 μg/mL, 375 μg/mL, or 750 μg/mL then stimulated to proliferate with concanavalin A (ConA). 4',6-diamidino-2-phenylindole (DAPI) and c...
Plasil M, Oppelt J, Klumplerova M, Bubenikova J, Vychodilova L, Janova E, Stejskalova K, Futas J, Knoll A, Leblond A, Mihalca AD, Horin P.The major histocompatibility complex (MHC) with its class I and II genes plays a crucial role in the immune response to pathogens by presenting oligopeptide antigens to various immune response effector cells. In order to counteract the vast variability of infectious agents, MHC class I and II genes usually retain high levels of SNPs mainly concentrated in the exons encoding the antigen binding sites. The aim of the study was to reveal new variability of selected MHC genes with a special focus on MHC class I physical haplotypes. Long-range NGS to was used to identify exon 2-exon 3 alleles in th...
Smith MA, Kristula MA, Aceto H, Levine DG.Fibrinogen and serum amyloid A (SAA) are commonly measured equine acute phase proteins. Limited data exist on SAA and fibrinogen responses to combination vaccination protocols in horses. A prospective cohort study evaluating SAA, fibrinogen, and rectal temperature following a standard combination vaccination. Blood for measurement of SAA and serum fibrinogen and rectal temperatures were obtained before (0 hour) and after vaccination (24, 48, 72, 96, 168 hours). After vaccination, SAA and fibrinogen increased in all horses. Imports had elevated SAA from 24-168 hours, whereas native horses retur...
Costa PWL, Oliveira CSM, Bezerra RA, Alvares FBV, Formiga VHAS, Martins MRDD, Feitosa TF, Vilela VLR.The aim of this study was to describe the prevalence of anti- and anti- antibodies in equids that carry out traction work in Northeastern Brazil, and to establish the potential risk factors associated with seropositivity for these agents. Blood samples were collected from 322 traction equids (horses, donkeys and mules) in urban areas of 16 municipalities in the State of Paraíba, Brazil. The samples were sent for serological diagnosis using the Immunofluorescence Antibody Test (IFAT). Epidemiological questionnaires were given to the owners to assess the possible risk factors associated with in...
Figueiredo MD, Vandenplas ML, Hurley DJ, Moore JN.Our understanding of the innate immune response in the horse has been limited by a lack of definitive data concerning cell signaling in response to microbial products. Toll-like receptors (TLRs) recognize conserved molecular motifs of microbes and elicit immune responses through their coupling with intracellular adaptor molecules, particularly MyD88 and TRIF. To provide a more definitive characterization of TLR signaling in the horse, the objectives of this study were to: (1) characterize the responses of equine monocytes to TLR ligands that signal through MyD88, TRIF or both in other species,...
Hong CB, Donahue JM, Giles RC, Petrites-Murphy MB, Poonacha KB, Roberts AW, Smith BJ, Tramontin RR, Tuttle PA, Swerczek TW.Pathologic and microbiologic examinations were performed on 1,211 aborted equine fetuses, stillborn foals, and placentas from premature foals in central Kentucky during the 1988 and 1989 foaling seasons to determine the causes of reproductive loss in the mare. Placentitis (19.4%) and dystocia-perinatal asphyxia (19.5%) were the 2 most important causes of equine reproductive loss. The other causes (in decreasing order) were contracted foal syndrome and other congenital anomalies (8.5%), twinning (6.1%), improper separation of placenta (4.7%), torsion of umbilical cord (4.5%), placental edema (4...
Battsetseg B, Lucero S, Xuan X, Claveria FG, Inoue N, Alhassan A, Kanno T, Igarashi I, Nagasawa H, Mikami T, Fujisaki K.The potential role of Boophilus microplus as a natural tick vector of Babesia equi and Babesia caballi in Brazilian horses was assessed using nested polymerase chain reaction (PCR)-based marker assay. B. equi merozoite-specific 218bp gene fragment was detected in almost 96% of horse blood samples, and 45.3-62.5% of females, eggs, larvae, and nymphs of B. microplus collected from 47 horses at Campo Grande in the State of Matto Grosso, Brazil. Except for the partially-fed female ticks, the B. caballi-specific 430bp gene fragment was amplified from horse blood samples, and all developmental stage...
Dhar M, Neilsen N, Beatty K, Eaker S, Adair H, Geiser D.Two studies report variability in proliferation and limited adipocyte differentiation of equine peripheral blood-derived adult mesenchymal stem cells, thus casting doubt on their adipogenic potential. Peripheral blood can be a valuable source of adult mesenchymal stem cells if cell culture conditions permissive for their adherence, proliferation and differentiation are defined. Hyperbaric oxygen treatment has been reported to mobilise haematopoietic progenitor stem cells into the peripheral blood in humans and mice, but similar experiments have not been done in horses. Objective: To optimise c...
Hedges JF, Balasuriya UB, Timoney PJ, McCollum WH, MacLachlan NJ.The persistently infected carrier stallion is the critical natural reservoir of equine arteritis virus (EAV), as venereal infection of mares frequently occurs after breeding to such stallions. Two Thoroughbred stallions that were infected during the 1984 outbreak of equine viral arteritis in central Kentucky subsequently became long-term EAV carriers. EAV genomes amplified from the semen of these two stallions were compared by sequence analysis of the six 3' open reading frames (ORFs 2 through 7), which encode the four known structural proteins and two uncharacterized glycoproteins. The major ...
Lin Q, Rikihisa Y.Diverse p44 alleles at the p44 expression locus (p44Es) encoding surface-exposed major membrane proteins, P44s, of Anaplasma phagocytophilum were hypothesized to be garnered by recombination to enact antigenic variation. However, this hypothesis has not been proven so far, due to inability to clone this obligate intragranulocytic rickettsia. To define the p44E recombination, we developed a novel method to clone A. phagocytophilum. This isogenic cloned population containing a defined p44E was used to infect a naive horse and severe combined immunodeficiency (SCID) mice. During a 58-day infectio...
Dubey JP, Davis SW, Speer CA, Bowman DD, de Lahunta A, Granstrom DE, Topper MJ, Hamir AN, Cummings JF, Suter MM.Sarcocystis neuronan n. sp. is proposed for the apicomplexan taxon associated with myeloencephalitis in horses. Only asexual stages of this parasite presently are known, and they are found within neuronal cells and leukocytes of the brain and spinal cord. The parasite is located in the host cell cytoplasm, does not have a parasitophorous vacuole, and divides by endopolygeny. Schizonts are 5-35 microns x 5-20 microns and contain 4-40 merozoites arranged in a rosette around a prominent residual body. Merozoites are approximately 4 x 1 micron, have a central nucleus, and lack rhoptries. Schizonts...
Esteves CL, Sheldrake TA, Dawson L, Menghini T, Rink BE, Amilon K, Khan N, Péault B, Donadeu FX.Mesenchymal stem/stromal cells (MSCs) have been used in human and equine regenerative medicine, and interest in exploiting their potential has increased dramatically over the years. Despite significant effort to characterize equine MSCs, the actual origin of these cells and how much of their native phenotype is maintained in culture have not been determined. In this study, we investigated the relationship between MSCs, derived from adipose tissue (AT) and bone marrow (BM), and pericytes in the horse. Both pericyte (CD146, NG2, and αSMA) and MSC (CD29, CD90, and CD73) markers were detected in ...
Williams KJ.Progressive lung fibrosis in humans, typified by idiopathic pulmonary fibrosis (IPF), is a serious cause of morbidity and mortality in people. Similar diseases have been described in dogs, cats, and horses. The cause and pathogenesis of such diseases in all species is poorly understood. There is growing evidence in human medicine that IPF is a manifestation of abnormal wound repair in response to epithelial injury. Because viruses can contribute to epithelial injury, there is increasing interest in a possible role of viruses, particularly gammaherpesviruses, in the pathogenesis of pulmonary fi...
Gilger BC, Malok E, Cutter KV, Stewart T, Horohov DW, Allen JB.Equine recurrent uveitis (ERU), a chronic, recurrent inflammation primarily of the anterior uveal tract, is the most common cause of blindness in horses. Recently, T-lymphocytes have been found to be the most numerous cell type to infiltrate the anterior uveal of horses with ERU. In the present study, we characterized the T-lymphocyte population in the anterior uveal tract of eyes of horses with chronic ERU by evaluating the microscopic appearance (histopathologic features), the T-lymphocyte subsets, and the relative levels and amounts of T-lymphocyte cytokine mRNA in the anterior uvea. Seven ...
de Vries AA, Glaser AL, Raamsman MJ, de Haan CA, Sarnataro S, Godeke GJ, Rottier PJ.Equine arteritis virus (EAV) is an enveloped, positive-stranded RNA virus belonging to the family Arteriviridae of the order Nidovirales. The unsegmented, infectious genome of EAV is 12,704 nt in length [exclusive of the poly(A) tail] and contains eight overlapping genes that are expressed from a 3'-coterminal nested set of seven leader-containing mRNAs. To investigate the importance of the overlapping gene arrangement in the viral life-cycle and to facilitate the genetic manipulation of the viral genome, a series of mutant full-length cDNA clones was constructed in which either EAV open readi...
Karagianni AE, Kapetanovic R, McGorum BC, Hume DA, Pirie SR.Alveolar macrophages (AMs) constitute the first line of defence in the lung of all species, playing a crucial role in the regulation of immune responses to inhaled pathogens. A detailed understanding of the function and phenotype of AMs is a necessary pre-requisite to both elucidating their role in preventing opportunistic bacterial colonisation of the lower respiratory tract and developing appropriate preventative strategies. The purpose of the study was to characterise this important innate immune cell at the tissue level by making functional and phenotypic comparisons with peritoneal macrop...
Parker JL, White KK.A complete search of the literature concerning Lyme borreliosis as it relates to horses and cattle was done. The epidemiology, pathogenesis, immunological response to the disease, diagnosis and treatment are discussed. A review of clinical cases in horses and cattle is presented. Clinical signs of Lyme borreliosis in horses include: chronic weight loss, sporadic lameness, laminitis, low grade fever, swollen joints, muscle tenderness, and anterior uveitis. In addition to those clinical signs, neurological signs such as depression, behavioral changes, dysphagia, head tilt and encephalitis can be...
Pigott JH, Ishihara A, Wellman ML, Russell DS, Bertone AL.To compare the clinical and inflammatory joint responses to intra-articular injection of bone marrow-derived mesenchymal stem cells (MSC) including autologous, genetically modified autologous, allogeneic, or xenogeneic cells in horses. Methods: Six five-year-old Thoroughbred mares had one fetlock joint injected with Gey's balanced salt solution as the vehicle control. Each fetlock joint of each horse was subsequently injected with 15 million MSC from the described MSC groups, and were assessed for 28 days for clinical and inflammatory parameters representing synovitis, joint swelling, and pain...
Rowland AL, Miller D, Berglund A, Schnabel LV, Levine GJ, Antczak DF, Watts AE.Allogeneic mesenchymal stromal cells (MSCs) have been used clinically for decades, without cross-matching, on the assumption that they are immune-privileged. In the equine model, we demonstrate innate and adaptive immune responses after repeated intra-articular injection with major histocompatibility complex (MHC) mismatched allogeneic MSCs, but not MHC matched allogeneic or autologous MSCs. We document increased peri-articular edema and synovial effusion, increased synovial cytokine and chemokine concentrations, and development of donor-specific antibodies in mismatched recipients compared wi...
Brindley MA, Maury W.Recently, it has become evident that entry of some retroviruses into host cells is dependent upon a vesicle-localized, low-pH step. The entry mechanism of equine infectious anemia virus (EIAV) has yet to be examined. Here, we demonstrate that wild-type strains of EIAV require a low-pH step for productive entry. Lysosomotropic agents that inhibit the acidification of internal vesicles inhibited productive entry of EIAV. The presence of ammonium chloride (30 mM), monensin (30 microM), or bafilomycin A (50 nM) in the medium dramatically decreased the number of EIAV antigen-positive cells. We foun...
Halliwell RE, McGorum BC, Irving P, Dixon PM.An enzyme-linked immunosorbent assay (ELISA) was used to quantify isotype-specific antibody to Micropolyspora faeni and to Aspergillus fumigatus in the sera and bronchoalveolar lavage fluid (BALF) of normal horses, horses with chronic obstructive pulmonary disease (COPD) and horses with other chronic respiratory diseases. Elevated antibody levels were not detected in the sera of affected horses. However, both IgE and IgA antibody to both allergens was significantly elevated in BALF in COPD affected horses sampled both when symptomatic and asymptomatic. Elevated levels were also found in animal...
MacLachlan NJ, Balasuriya UB, Hedges JF, Schweidler TM, McCollum WH, Timoney PJ, Hullinger PJ, Patton JF.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, an apparently emerging disease of equids. In this study, the antibody response of horses to the structural proteins of EAV was evaluated using gradient-purified EAV virions and baculovirus-expressed recombinant EAV structural proteins (G(L), G(S), M, N) as antigens in a Western immunoblotting assay. Thirty-three sera from horses that previously had been naturally or experimentally infected with EAV were evaluated, including samples from mares, geldings, and both persistently and nonpersistently infected stallions. S...
Deeg CA, Ehrenhofer M, Thurau SR, Reese S, Wildner G, Kaspers B.Equine recurrent uveitis (ERU) is the most serious eye disease in horses worldwide. Despite the fact that ERU is generally considered to be immune mediated, a detailed description of the histopathology of the posterior part of ERU eyes is lacking. Here, we examined sections of paraffin-embedded eyes using histological and immunhistological methods. Twenty seven eyes of 20 horses with ERU and 30 eyes of 15 healthy control horses were included in this study. We could consistently demonstrate an involvement of the retina and the choroid in all examined eyes of horses with spontaneous ERU. In eyes...
Rikihisa Y, Pretzman CI, Johnson GC, Reed SM, Yamamoto S, Andrews F.Ehrlichia risticii has a close antigenic relationship to E. sennetsu. Sera of ponies experimentally infected with E. risticii, the etiologic agent of Potomac horse fever, consistently reacted with E. sennetsu, a human pathogen, in indirect fluorescent-antibody (IFA) testing, while human E. sennetsu convalescent serum reacted with E. risticii by IFA testing and immunoferritin labeling of cells infected in vitro. Two ponies injected intravenously with live E. sennetsu did no develop clinical illness. Subsequent injection with live E. sennetsu did not develop clinical illness. Subsequent injectio...
Müller J, Feige K, Wunderlin P, Hödl A, Meli ML, Seltenhammer M, Grest P, Nicolson L, Schelling C, Heinzerling LM.Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmi...
Hatanaka H, Iourin O, Rao Z, Fry E, Kingsman A, Stuart DI.The Gag polyprotein is key to the budding of retroviruses from host cells and is cleaved upon virion maturation, the N-terminal membrane-binding domain forming the matrix protein (MA). The 2.8-A resolution crystal structure of MA of equine infectious anemia virus (EIAV), a lentivirus, reveals that, despite showing no sequence similarity, more than half of the molecule can be superimposed on the MAs of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV). However, unlike the structures formed by HIV-1 and SIV MAs, the oligomerization state observed is not trimeric...
MacLachlan NJ, Balasuriya UB, Hedges JF, Schweidler TM, McCollum WH, Timoney PJ, Hullinger PJ, Patton JF.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, an apparently emerging disease of equids. In this study, the antibody response of horses to the structural proteins of EAV was evaluated using gradient-purified EAV virions and baculovirus-expressed recombinant EAV structural proteins (G(L), G(S), M, N) as antigens in a Western immunoblotting assay. Thirty-three sera from horses that previously had been naturally or experimentally infected with EAV were evaluated, including samples from mares, geldings, and both persistently and nonpersistently infected stallions. S...
Luo J, Bruice TC.Molecular dynamics and cross-correlation analysis of the horse liver alcohol dehydrogenase HLADH.NAD(+).PhCH(2)O(-) complex has established anticorrelated motions between the NAD(+)-binding domain and other portions of the enzyme. Four pairs of anticorrelated interactions are (i and ii) cofactor-binding domain: C(alpha) of V292 and the CG1 of V203 with C7 of PhCH(2)O(-); (iii) cofactor-binding domain: amide carbonyl oxygen of I318 with amide N of H67; and (iv) cofactor domain: C(alpha) of T178 with carbonyl oxygen of L141. The average distances between pairs are 9.2 A for i, 8.2 A for ii, 14.7...
Chang YF, Novosol V, McDonough SP, Chang CF, Jacobson RH, Divers T, Quimby FW, Shin S, Lein DH.Seven specific-pathogen-free (SPF) ponies, 1-5 years old, were exposed to Borrelia burgdorferi-infected adult ticks while being treated with dexamethasone over 5 consecutive days. One SPF pony (pony No. 178) was first exposed to laboratory-reared nymphs without B. burgdorferi infection and 3 weeks later was exposed to B. burgdorferi-infected adult ticks with concurrent dexamethasone treatment for 5 consecutive days. Four uninfected ponies treated with dexamethasone, exposed to laboratory-reared ticks without B. burgdorferi infection served as uninfected controls. Clinical signs, bacteriologic ...
Adams AA, Breathnach CC, Katepalli MP, Kohler K, Horohov DW.A number of model systems have been employed to investigate age-associated changes in immune function. The purpose of the current study was to characterize senescent T cells and to investigate the inflamm-aging phenomenon both in vitro and in vivo using the old horse as a model. We examined whether decreased T cell proliferation induced by Con A is caused by increased apoptosis. We also utilized intracellular CFSE to analyze changes within each round of cell proliferation, in particular cytokine production. Intracellular staining with flow cytometry, RT-PCR, and ELISA were used to measure pro-...
Tallmadge RL, Lear TL, Antczak DF.The availability of a contig of bacterial artificial chromosome (BAC) clones spanning the equine major histocompatibility complex (MHC) made possible a detailed analysis of horse MHC class I genes. Prior to this study, only a single horse MHC class I gene had been sequenced at the genomic level. Although many ( approximately 60) MHC class I cDNA sequences had been determined and published, from this information, it was not possible to determine how many class I loci are expressed in horses or to assign individual sequences to allelic series. In this study, 15 MHC class I genes were identified ...
Velie BD, Shrestha M, Franҫois L, Schurink A, Tesfayonas YG, Stinckens A, Blott S, Ducro BJ, Mikko S, Thomas R, Swinburne JE, Sundqvist M....While susceptibility to hypersensitive reactions is a common problem amongst humans and animals alike, the population structure of certain animal species and breeds provides a more advantageous route to better understanding the biology underpinning these conditions. The current study uses Exmoor ponies, a highly inbred breed of horse known to frequently suffer from insect bite hypersensitivity, to identify genomic regions associated with a type I and type IV hypersensitive reaction. A total of 110 cases and 170 controls were genotyped on the 670K Axiom Equine Genotyping Array. Quality control ...
Rwambo PM, Issel CJ, Hussain KA, Montelaro RC.A neutralization escape mutant (A/1 E) of equine infectious anemia virus was isolated after 13 passages in cell culture in the presence of serum containing antibodies to type- and group-specific determinants of EIAV envelope glycoproteins. Loss of neutralization by the selecting serum correlated with loss of two epitopes in the major envelope glycoprotein gp90 of A/1 E which were present in a parallel variant isolated from a persistently infected pony.
Khusro A, Aarti C, Rivas-Caceres RR, Barbabosa-Pliego A.Equine herpesvirus-1 (EHV-1) is one of the most common and ubiquitous viral pathogens infecting equines, particularly horses worldwide. The EHV-1 is known to induce not only humoral but also cellular immune responses in horses. Respiratory distress, abortion in pregnant mares, neurological disorders, and neonatal foal deaths represent EHV-1 infection. Despite the limited success of inactivated, subunit, live, and DNA vaccines, over the past few decades, vaccination remains the prime preventive option to combat EHV-1 infection in horses. However, current vaccines lack the potentiality to protec...
