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.
Svala E, Löfgren M, Sihlbom C, Rüetschi U, Lindahl A, Ekman S, Skiöldebrand E.The molecular aspects of inflammation were investigated in equine articular cartilage explants using quantitative proteomics. Articular cartilage explants were stimulated with interleukin (IL)-1β in vitro for 25 days, and proteins released into cell culture media were chemically labeled with isobaric mass tags and analyzed by liquid chromatography-tandem mass spectrometry. A total of 127 proteins were identified and quantified in media from explants. IL-1β-stimulation resulted in an abundance of proteins related to inflammation, including matrix metalloproteinases, acute phase proteins, comp...
Meulenbroeks C, van der Lugt JJ, van der Meide NM, Willemse T, Rutten VP, Zaiss DM.The immunological mechanisms explaining development of an allergy in some individuals and not in others remain incompletely understood. Insect bite hypersensitivity (IBH) is a common, seasonal, IgE-mediated, pruritic skin disorder that affects considerable proportions of horses of different breeds, which is caused by bites of the insect Culicoides obsoletus (C. obsoletus). We investigated the allergen-specific immune status of individual horses that had either been diagnosed to be healthy or to suffer of IBH. Following intradermal allergen injection, skin biopsies were taken of IBH-affected an...
Remacha AR, Barrachina L, Álvarez-Arguedas S, Ranera B, Romero A, Vázquez FJ, Zaragoza P, Yañez R, Martín-Burriel I, Rodellar C.The immunomodulatory capacities of mesenchymal stem cells (MSCs) have made them the subject of increased clinical interest for tissue regeneration and repair. We have studied the immunomodulatory capacity of equine MSCs derived from bone marrow (BM-MSCs) and adipose tissue (AT-MSCs) in cocultures with allogeneic peripheral blood mononuclear cells (PBMCs). Different isoforms and concentrations of phytohaemaglutinin (PHA) were tested to determine the best stimulation conditions for PBMC proliferation and a proliferation assay was performed for 7 days to determine the optimal day of stimulation o...
Kol A, Wood JA, Carrade Holt DD, Gillette JA, Bohannon-Worsley LK, Puchalski SM, Walker NJ, Clark KC, Watson JL, Borjesson DL.Intravenous (IV) injection of mesenchymal stem cells (MSCs) is used to treat systemic human diseases and disorders but is not routinely used in equine therapy. In horses, MSCs are isolated primarily from adipose tissue (AT) or bone marrow (BM) and used for treatment of orthopedic injuries through one or more local injections. The objective of this study was to determine the safety and lymphocyte response to multiple allogeneic IV injections of either AT-derived MSCs (AT-MSCs) or BM-derived MSCs (BM-MSCs) to healthy horses. Methods: We injected three doses of 25 × 10(6) allogeneic MSCs fro...
Pezzanite LM, Fortier LA, Antczak DF, Cassano JM, Brosnahan MM, Miller D, Schnabel LV.This study tested the hypothesis that Major Histocompatibility Complex (MHC) incompatible equine mesenchymal stromal cells (MSCs) would induce cytotoxic antibodies to donor MHC antigens in recipient horses after intradermal injection. No studies to date have explored recipient antibody responses to allogeneic donor MSC transplantation in the horse. This information is critical because the horse is a valuable species for assessing the safety and efficacy of MSC treatment prior to human clinical application. Methods: Six MHC heterozygote horses were identified as non-ELA-A2 haplotype by microsat...
Gajos K, Kozdrowski R, Nowak M, Siemieniuch MJ.Mares that fail to become pregnant after repeated breeding, without showing typical signs of clinical endometritis, should be suspected of subclinical endometritis (SE). Contact with infectious agents results in altered synthesis and secretion of inflammatory mediators, including cytokines and arachidonic acid metabolites, and disturbs endometrial functional balance. To address the hypothesis that SE affects the immune endocrine status of the equine endometrium, spontaneous secretion of prostaglandin E(2) (PGE(2)), prostaglandin F(2α) (PGF(2α)), 6-keto-PGF(1α )(a metabolite of prostacyclin ...
Kravtsov AL.Compare the content of bactericidal granules (BG) in blood phagocytes of animals, that differ by species sensitivity to plague infection, under the conditions of measuring, that ensure automatic differentiating by this parameter of monocytes and granulocytes of human blood. Methods: Human whole blood leukocytes were studied, as well as from 7 animal species: mice, guinea pigs, golden hamsters, white rats, rabbits, dogs and horses. Acridine orange (AO) was used for supra-vital staining in primary (bactericidal) granule cells. Relative BG content was measured in separate cells in conventional un...
Woodward EM, Troedsson MH.Transient post breeding endometritis is a normal physiological reaction in the mare, as it is believed that an inflammatory response is necessary for the effective removal of contaminating bacteria and excess spermatozoa introduced into the uterus. While most mares can clear endometritis within a reasonable amount of time, persistent endometritis caused by either bacteria or spermatozoa can threaten the success of a pregnancy. A subpopulation of mares is susceptible to persistent endometritis, and these mares are a concern in equine reproductive medicine. Research has identified several factor...
Wobeser BK.During a widespread anthrax outbreak in Canada, miniature horses were vaccinated using a live spore anthrax vaccine. Several of these horses died from an apparent immune-mediated vasculitis temporally associated with this vaccination. During the course of the outbreak, other miniature horses from different regions with a similar vaccination history, clinical signs, and necropsy findings were found. Vaccin contre l’anthrax associé à la mort de chevaux miniatures. Durant une vaste éclosion d’anthrax au Canada, des chevaux miniatures ont été vaccinés en utilisant un vaccin à base de sp...
Zabrecky KA, Slovis NM, Constable PD, Taylor SD.Accurate diagnostic markers for sepsis in neonatal foals are needed. Plasma C-reactive protein concentration (p[CRP]) and haptoglobin concentration (p[Hp]) are well-established biomarkers of infection in humans, but studies are lacking in foals. Objective: p[CRP]) and p[Hp] are increased in septic foals compared to sick nonseptic and healthy control foals, and are predictive of survival. Methods: Eighty critically ill foals (40 septic, 40 sick nonseptic) and 39 healthy control foals <1 week of age. Methods: Multicenter, prospective observational clinical study. Venous blood was collected at a...
Hoffman CJ, McKenzie HC, Furr MO, Desrochers A.Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis occurs in horses with systemic inflammatory response syndrome (SIRS). Peripheral resistance to glucocorticoids has not been investigated in horses. Objective: To determine if glucocorticoid receptor (GR) function in horses can be measured using flow cytometry, and to use this information to evaluate HPA axis dynamics. Methods: Eleven healthy adult horses in parts 1 and 2. Ten horses with SIRS and 10 age and sex matched controls in part 3. Methods: Flow cytometry was used to evaluate GR density and binding affinity (BA) in 3 healthy...
Mask TA, Schoenecker KA, Kane AJ, Ransom JI, Bruemmer JE.Immunocontraception with porcine ZP (pZP) can be an effective means of fertility control in feral horses. Previous studies suggest that antibodies produced after pZP vaccination may both inhibit fertilization and cause follicular dysgenesis. Zonastat-H, PZP-22, and SpayVac are three pZP vaccines proposed for use in horses. Although all these vaccines contain the pZP antigen, variations in antigen preparation and vaccine formulation lead to differences in antigenic properties among them. Likewise, despite numerous efficacy and safety studies of Zonastat-H and PZP-22, the contraceptive mechanism...
McLean R, Rash NL, Robinson C, Waller AS, Paillot R.Streptococcus equi subspecies equi (S. equi) is the causative agent of strangles, a highly contagious upper respiratory disease of equids. Streptococcus equi produces superantigens (sAgs), which are thought to contribute to strangles pathogenicity through non-specific T-cell activation and pro-inflammatory response. Streptococcus equi infection induces abscesses in the lymph nodes of the head and neck. In some individuals, some abscess material remains into the guttural pouch and inspissates over time to form chondroids which can harbour live S. equi. The aim of this study was to determine...
Ranera B, Antczak D, Miller D, Doroshenkova T, Ryan A, McIlwraith CW, Barry F.Recently, it has been shown that mesenchymal stem cells (MSCs) do not express the major histocompatibility complex (MHC) II antigen and are able to inhibit proliferation of MHC-mismatched stimulated lymphocytes, enabling their use as in vivo allogeneic transplants. However, prior to clinical application of allo-MSCs, in vitro tests are required to confirm the safety of treatment protocols. Objective: To evaluate the immunosuppressive capabilities of equine bone-marrow-derived MSCs (BM-MSCs) on MHC-mismatched lymphocytes. Methods: In vitro experiment. Methods: Phytohaemagglutinin-stimulated per...
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...
Ortved K, Wagner B, Calcedo R, Wilson J, Schaefer D, Nixon A.Intraarticular (IA) administration of viral vectors expressing a therapeutic transgene is an attractive treatment modality for osteoarthritis (OA) as the joint can be treated as a contained unit. Humoral and cell-mediated immune responses in vivo can limit vector effectiveness. Transduction of articular tissues has been investigated; however, the immune response to IA vectors remains largely unknown. We hypothesized that IA rAAV2 and rAAV5 overexpressing insulin-like growth factor-I (IGF-I) would result in long-term IGF-I formation but would also induce neutralizing antibodies (NAb) and anti-c...
Sánchez-Matamoros A, Beck C, Kukielka D, Lecollinet S, Blaise-Boisseau S, Garnier A, Rueda P, Zientara S, Sánchez-Vizcaíno JM.African horse sickness (AHS) is a viral disease that causes high morbidity and mortality rates in susceptible Equidae and therefore significant economic losses. More rapid, sensitive and specific assays are required by diagnostic laboratories to support effective surveillance programmes. A novel microsphere-based immunoassay (Luminex assay) in which beads are coated with recombinant AHS virus (AHSV) structural protein 7 (VP7) has been developed for serological detection of antibodies against VP7 of any AHSV serotype. The performance of this assay was compared with that of a commercial enzyme-l...
Nielsen MK, Rubinson EF, Chambers TM, Horohov DW, Wagner B, Betancourt A, Reedy SE, Jacobsen S.Anthelmintics and vaccines are commonly given concurrently in routine equine management, but it is unknown to what extent an interaction between the two exists. Cyathostomins can modulate the local immune response by stimulating a type 2 helper T cell (Th2) response. In addition, anti-inflammatory effects of ivermectin have been found in rodent models. It is unknown whether these anti-inflammatory effects affect the acute phase response elicited by commonly used vaccines. This study evaluated how the acute phase inflammatory response, leukocyte expression of pro-inflammatory cytokines, and vac...
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...
Valle E, Zanatta R, Odetti P, Traverso N, Furfaro A, Bergero D, Badino P, Girardi C, Miniscalco B, Bergagna S, Tarantola M, Intorre L, Odore R.The aim of the study was to evaluate markers of the acute phase response (APR) in eventing horses by measuring acute phase proteins (APP) (haptoglobin, Hp, and serum amyloid A, SAA), lysozyme, protein adducts such as pentosidine-like adducts (PENT), malondialdehyde adducts (MDA), hydroxynonenal adducts (HNE) and total advanced glycation/glycoxidation end products (AGEs), complete blood count and lymphocyte subpopulations (CD4+, CD8+ and CD21+) both at rest and at the end of an eventing competition. Blood samples were collected from eight Warmblood horses (medium age 10 ± 3) during an offici...
Sanz MG, Villarino N, Ferreira-Oliveira A, Horohov DW.Rhodococcus equi is a common cause of pneumonia in young foals worldwide and has considerable economic effects on the global equine industry. Despite ongoing efforts, no vaccine is currently available to prevent rhodococaal pneumonia. This is due, in part, to an incomplete understanding of the protective immune response to this bacterium. While antibodies to VapA, a lipoprotein produced by virulent R. equi, are useful in differentiating antibody production in response to pathogenic versus non-pathogenic strains, the significance of the humoral response of foals to this lipoprotein remains poor...
Frellstedt L, Gosset P, Kervoaze G, Hans A, Desmet C, Pirottin D, Bureau F, Lekeux P, Art T.Respiratory diseases, including inflammatory airway disease (IAD), viral and bacterial infections, are common problems in exercising horses. The airway epithelium constitutes a major physical barrier against airborne infections and plays an essential role in the lung innate immune response mainly through toll-like receptor (TLR) activation. The aim of this study was to develop a model for the culture of equine bronchial epithelial cells (EBEC) in vitro and to explore EBEC innate immune responses in trained horses. Bronchial epithelial biopsies were taken from 6 adult horses during lower airway...
Robinson C, Heather Z, Slater J, Potts N, Steward KF, Maskell DJ, Fontaine MC, Lee JJ, Smith K, Waller AS.Strangles, caused by Streptococcus equi subspecies equi (S. equi) is one of the most frequently diagnosed infectious diseases of horses and there remains a significant need to develop new preventative vaccines. We generated a live vaccine strain of S. equi containing deletions in six genes: sagA, hasA, aroB, pyrC, seM and recA, which was administered to nine Welsh mountain ponies via the intramuscular route. Four vaccinated ponies developed adverse reactions following the first vaccination from which the live vaccine strain was isolated. Two of these ponies were withdrawn from the study and se...
Taylor S.Sepsis is defined as an exaggerated, systemic inflammatory response to infection and is a common condition in horses. Systemic inflammatory response syndrome (SIRS) associated with bacterial infection is a hallmark of sepsis. Sepsis in neonatal foals is a common sequela of failure of passive transfer and, in addition to development of SIRS, may be characterised by bacteraemia, pneumonia, enterocolitis, omphalophlebitis, meningoencephalitis or arthritis. Sepsis in mature horses is most commonly observed secondary to gastrointestinal lesions that result in disrupted mucosa and bacterial transloc...
Perkins GA, Wagner B.The development of equine immunity from the fetus to adulthood is complex. The foal's immune response and the immune mechanisms that they are equipped with, along with changes over the first months of life until the immune system becomes adult-like, are only partially understood. While several innate immune responses seem to be fully functional from birth, the onset of adaptive immune response is delayed. For some adaptive immune parameters, such as immunoglobin (Ig)G1, IgG3, IgG5 and IgA antibodies, the immune response starts before or at birth and matures within 3 months of life. Other antib...
Davis EG, Bello NM, Bryan AJ, Hankins K, Wilkerson M.Protection from infectious disease requires antigen-specific immunity. In foals, most vaccine protocols are delayed until 6 months to avoid maternal antibody interference. Susceptibility to disease may exist prior to administration of vaccination at age 4-6 months. Objective: The aim of this investigation was to characterise immune activation among healthy foals in response to a multivalent vaccine protocol and compare immune responses when foals were vaccinated at age either 90 or 180 days. Methods: Randomised block design. Methods: Twelve healthy foals with colostral transfer were blocked fo...
Bullone M, Lavoie JP.Animal models have been studied to unravel etiological, immunopathological, and genetic attributes leading to asthma. However, while experiments in which the disease is artificially induced have helped discovering biological and molecular pathways leading to allergic airway inflammation, their contribution to the understanding of the causality of the disease has been more limited. Horses naturally suffer from an asthma-like condition called "heaves" which presents sticking similarities with human asthma. It is characterized by reversible airway obstruction, airway neutrophilic inflammation, an...
Do Carmo GM, Da Silva AS, Klauck V, Pazinato R, Moura AB, Duarte T, Duarte MM, Bochi GV, Moresco RN, Stefani LM.Toxoplasmosis is an important parasitic disease affecting several species of mammals, but little is known about this disease in horses. This study aimed to investigate the levels of several immunological variables and markers of cell damage in the serum of seropositive horses for Toxoplasma gondii. Sera samples of adult horses from the Santa Catarina State, Brazil used on a previous study were divided into groups according to their antibody levels for T. gondii determined by immunofluorescence assay, i.e. 20 samples from seronegative horses (Group A - control), 20 samples from horses with tite...
Bielefeldt-Ohmann H, Prow NA, Wang W, Tan CS, Coyle M, Douma A, Hobson-Peters J, Kidd L, Hall RA, Petrovsky N.In 2011, following severe flooding in Eastern Australia, an unprecedented epidemic of equine encephalitis occurred in South-Eastern Australia, caused by Murray Valley encephalitis virus (MVEV) and a new variant strain of Kunjin virus, a subtype of West Nile virus (WNVKUN). This prompted us to assess whether a delta inulin-adjuvanted, inactivated cell culture-derived Japanese encephalitis virus (JEV) vaccine (JE-ADVAX™) could be used in horses, including pregnant mares and foals, to not only induce immunity to JEV, but also elicit cross-protective antibodies against MVEV and WNVKUN. Foals, 74...
Janda J, Lehmann M, Luttmann W, Marti E.Interleukin-3 is a growth and differentiation factor for various hematopoietic cells. IL-3 also enhances stimulus-dependent release of mediators and cytokine production by mature basophils. Function of IL-3 has not been studied in horses because of lack of horse-specific reagents. Our aim was to produce recombinant equine IL-3 and test its effect on sulfidoleukotriene and cytokine production by equine peripheral blood leukocytes (PBL). Equine IL-3 was cloned, expressed in E. coli and purified. PBL of 19 healthy and 20 insect bite hypersensitivity (IBH)-affected horses were stimulated with Culi...
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...
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 ...
Sheoran AS, Artiushin S, Timoney JF.The intranasal immunogenicity of cholera toxin (CT) genetically coupled to peptide sequence aa236-334 (F3) of the SeM protein of Streptococcus equi was studied in five young adult Welsh ponies. All ponies made rapid CTB- and SeMF3-specific serum antibody responses following the first immunization. Specific nasal IgA responses were detected in two ponies 14 days after the first immunization, in another two 14 days after a second immunization on day 14, and in all ponies 28 days after a third immunization on day 42. SeMF3-specific antibody responses in sera and nasal washes were dominated by IgG...
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...
Lucassen A, Hankel J, Finkler-Schade C, Osbelt L, Strowig T, Visscher C, Schuberth HJ.Feed supplements such as fermentation products (SCFP) alter immune responses in horses. The purpose of this study was to analyze whether a prebiotic activity of the SCFP alters the gut microbiome in horses. Racehorses were fed either SCFP (Olimond BB, OLI, = 6) or placebo pellets (PLA, = 5) for 43 days. Fecal microbiota analysis was performed using 16S rRNA gene sequencing. The numbers and function of circulating immune cell subpopulations were analyzed by flow cytometry. SCFP supplementation resulted in non-consistent differences in fecal microbiota between the PLA and OLI during the feedi...
Depuydt E, Broeckx SY, Chiers K, Patruno M, Da Dalt L, Duchateau L, Saunders J, Pille F, Martens A, Van Hecke L, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine tendon disease is widely investigated because of their regenerative and immunomodulatory potential. However, questions have been raised concerning the immunogenic properties of allogeneic MSCs. Therefore, two studies were conducted to assess the safety of equine allogeneic peripheral blood-derived tenogenic primed MSCs (tpMSCs). The objective was to evaluate if a single and repeated tpMSC administration induced a cellular and humoral immune response in horses suffering from tendon injuries. Horses enrolled in the first study ...
Bidaud P, Hébert L, Barbey C, Appourchaux AC, Torelli R, Sanguinetti M, Laugier C, Petry S.Rhodococcus equi is one of the most widespread causes of disease in foals aged from 1 to 6 months. R. equi possesses antioxidant defense mechanisms to protect it from reactive oxygen metabolites such as hydrogen peroxide (H(2)O(2)) generated during the respiratory burst of phagocytic cells. These defense mechanisms include enzymes such as catalase, which detoxify hydrogen peroxide. Recently, an analysis of the R. equi 103 genome sequence revealed the presence of four potential catalase genes. We first constructed ΔkatA-, ΔkatB-, ΔkatC-and ΔkatD-deficient mutants to study the ability of R. ...
O'Neill W, McKee S, Clarke AF.This study was undertaken to compile new data on the efficacy of Echinacea in stimulating the immune system of the horse. Use of Echinacea is becoming widespread in horses, despite an absence of controlled laboratory research into its effectiveness or safety. This paper documents results of a double-blind, placebo-controlled, cross-over trial investigating the effect of standardised Echinacea extract on 8 horses. Animals were supplemented with Echinacea or placebo for 42 days, and their response to supplements recorded. Treatment with Echinacea increased phagocytic ability of isolated neutroph...
Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V.Lipopolysaccharide (endotoxin, LPS) is a strong inducer of the innate immune response. It is widespread in our environment, e.g. in house dust and contributes to asthma. Compared to humans, horses are even more sensitive to LPS. However, data on LPS effects on the equine transcriptome are very limited. Using RNA-seq we analysed LPS-induced differences in the gene expression in equine peripheral blood mononuclear cells at the gene and gene-network level in two half-sib families and one group of unrelated horses. 24 h-LPS challenge of equine immune cells resulted in substantial changes in the t...
Van Cleemput J, Poelaert KCK, Laval K, Vanderheijden N, Dhaenens M, Daled S, Boyen F, Pasmans F, Nauwynck HJ.β-Defensins protect the respiratory tract against the myriad of microbial pathogens entering the airways with each breath. However, this potentially hostile environment is known to serve as a portal of entry for herpesviruses. The lack of suitable respiratory model systems has precluded understanding of how herpesvirus virions overcome the abundant mucosal β-defensins during host invasion. We demonstrate how a central alphaherpesvirus, equine herpesvirus type 1 (EHV1), actually exploits β-defensins to invade its host and initiate viral spread. The equine β-defensins (eBDs) eBD1, -2, and -3...
Chung C, Mealey RH, McGuire TC.Cytotoxic T lymphocytes (CTL) are critical for lentivirus control including EIAV. Since CTL from most EIAV carrier horses recognize Gag epitope clusters (EC), the hypothesis that carrier horses would have high functional avidity CTL to optimal epitopes in Gag EC was tested. Twenty-two optimal EC epitopes were identified; two in EC1, six in EC2, and seven each in EC3 and 4. However, only five of nine horses had high functional avidity CTL (<or=11 nM) recognizing six epitopes in EC; four in relatively conserved EC3; and one each in EC1 and 2. Horses with high functional avidity CTL had signif...
Equine recurrent uveitis serves as a spontaneous model for human autoimmune uveitis. Unpredictable relapses and ongoing inflammation in the eyes of diseased horses as well as in humans lead to destruction of the retina and finally result in blindness. However, the molecular mechanisms leading to inflammation and retinal degeneration are not well understood. An initial screening for differentially regulated proteins in sera of uveitic cases compared to healthy controls revealed an increase of the alternative pathway complement component factor B in ERU cases. To determine the activation status ...
Gilger BC, Salmon JH, Yi NY, Barden CA, Chandler HL, Wendt JA, Colitz CM.To determine the role of intraocular bacteria in the pathogenesis of equine recurrent uveitis (ERU) in horses from the southeastern United States by evaluating affected eyes of horses with ERU for bacterial DNA and intraocular production of antibodies against Leptospira spp. Methods: Aqueous humor, vitreous humor, and serum samples of 24 clinically normal horses, 52 horses with ERU, and 17 horses with ocular inflammation not associated with ERU (ie, non-ERU inflammation). Methods: Ribosomal RNA quantitative PCR (real-time PCR) assay was used to detect bacterial DNA in aqueous humor and vitreou...
Simonen-Jokinen T, Pirie RS, McGorum BC, Maisi P.Airway matrix metalloproteinases (MMPs) increase following inhalation of organic dust. The relative contribution of dust components to this elevation is unknown. Objective: To identify components of organic dust responsible for elevated MMP levels in equine airways. Methods: Bronchoalveolar lavage (BALF) from 7 heaves-susceptible horses, collected 6 h following inhalation challenges with saline, 2 different hay dust suspensions (HDS-1 and -2) and soluble and particulate fractions of HDS-1, were analysed for MMP-2 and -9 using SDS-page gelatin zymography. Results: HDS-1 challenge increased BALF...
Sarkar S, Balasuriya UB, Horohov DW, Chambers TM.Equine herpesvirus-1 (EHV-1) is a major respiratory viral pathogen of horses, causing upper respiratory tract disease, abortion, neonatal death, and neurological disease that may lead to paralysis and death. EHV-1 replicates initially in the respiratory epithelium and then spreads systemically to endothelial cells lining the small blood vessels in the uterus and spinal cord leading to abortion and EHM in horses. Like other herpesviruses, EHV-1 employs a variety of mechanisms for immune evasion including suppression of type-I interferon (IFN) production in equine endothelial cells (EECs). Previ...
Dixon JB, Jenkins P, Allan D.Culture of murine lymph node cells together with living protoscolices of Echinococcus granulosus is described. The presence of the parasite induced potent blastic transformation in lymphocytes of unimmunized mice as indicated by tritiated thymidine incorporation. The response was markedly reduced by killing the parasite immediately prior to culture. No blastogenic activity was detectable in supernatants from living parasites cultured alone. Protoscolices from artificially infected syngeneic mice were effective stimuli, as were protoscolices from naturally infected horse and sheep. Stimulation ...
Tabynov K, Kydyrbayev Z, Ryskeldinova S, Assanzhanova N, Kozhamkulov Y, Inkarbekov D, Sansyzbay A.To design and evaluate the safety and immunogenicity of a modified-live vaccine to prevent equine influenza virus (EIV) infection based on the novel reassortant cold-adapted strain A/HK/Otar/6:2/2010. Methods: Surface proteins (HA, NA) from the wild-type strain A/equine/Otar/764/2007 (H3N8) and internal proteins (PB2, PB1, PA, NP, M, NS) from the attenuated cold-adapted donor strain A/Hong Kong/1/68/162/35CA (H3N2) were included in the vaccine. Horses were administered 10(9.2) EID50 /mL of the modified-live vaccine or saline solution using a nasal spray. The clinical condition of the animals w...
Newman MJ, Issel CJ, Truax RE, Powell MD, Horohov DW, Montelaro RC.Suppression of the immune system is a common aspect of the disease pathogenesis associated with retroviral infections in both man and animals. We have measured transient suppression of the equine immune system as a loss or decrease in antigen-specific and polyclonal lymphocyte proliferation following experimental infection of ponies with three variants of equine infectious anemia virus (EIAV) with difference virulence characteristics. The transient suppression of proliferative responses was temporally associated with recurrent febrile episodes, which are the hallmark symptom of EIAV-induced di...
Steelman SM, Johnson D, Wagner B, Stokes A, Chowdhary BP.Chronic equine laminitis causes persistent pain and lameness in affected animals and often necessitates euthanasia when pain management strategies become ineffective. Published studies as well as anecdotal reports suggest that this chronic inflammatory disease is associated with systemic alterations in immune responsiveness, perhaps involving an autoimmune component. We investigated this broad hypothesis by measuring a variety of immune indicators in healthy control horses (CON) and horses with chronic laminitis (LMN). We found that white blood cells from LMN horses produced more IFNγ than di...
Wagnerová P, Sak B, Květoňová D, Maršálek M, Langrová I, Kváč M.A total of 9 (8 stallions and 1 mare) 1 year old ponies were used for the experimental infection caused by Encephalitozoon cuniculi genotype II (10(7) spores per animal). Subsequently, individual horses were slaughtered 7, 14, 21, 28, 35, 42, 49, 56, and 63 days post infection. Immediately after slaughter, tissues samples of stomach, duodenum, jejunum, ileum, caecum, colon, spleen, liver, kidney, bladder, heart, lungs, and brain were sampled. In addition, urine, feces and blood specimens were collected. Enzyme-linked immunosorbent assay was used for determination of humoral immune response and...
REBERS PA, HURWITZ E, HEIDELBERGER M.Rebers, Paul A. (Rutgers University, New Brunswick, N. J.), Esther Hurwitz, and Michael Heidelberger. Immunochemistry of pneumococcal types II, V, and VI. II. Inhibition tests in the type VI precipitating system. J. Bacteriol. 82:920-926. 1961.-As in other immune systems involving polysaccharides, rabbit antibodies but not those engendered in the horse were found sensitive to degradation of type VI pneumococcal (Pn) polysaccharide (SVI), and were readily inhibited by fragments of SVI. Large amounts, 30 to 111 mumoles, of most sugars gave up to 15% inhibition, while sugar and polyol phosphates ...
Jonsdottir S, Svansson V, Stefansdottir SB, Mäntylä E, Marti E, Torsteinsdottir S.Insect bite hypersensitivity is an immunoglobulin (Ig)E-mediated dermatitis of horses initiated by bites of midges of the genus Culicoides. Culicoides spp. are not indigenous to Iceland and the prevalence of insect bite hypersensitivity is much higher in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. Immunotherapy is therefore needed. Objective: The aim of the study was to express an allergen from Culicoides in barley grain and investigate whether an immune response could be obtained in healthy Icelandic horses by oral treatment with ...
Hansen S, Sun L, Baptiste KE, Fjeldborg J, Horohov DW.Diseases of the lower airways represent some of the most common conditions affecting horses of all ages, but the type and severity tends to follow the horses' age. The age-related dysregulation of pro-inflammatory cytokines may, in part contribute to the development of the diseases. Therefore, we hypothesize that the expression of pro-inflammatory cytokines increases with age. Peripheral blood mononuclear cells (PBMC) and bronchoalveolar lavage (BAL) cells from clinically healthy horses of different ages were used for the investigation. The cells were stimulated and the production of IFN-γ an...
Thompson MK, Fridy PC, Keegan S, Chait BT, Fenyö D, Rout MP.Antibodies made in large animals are integral to many biomedical research endeavors. Domesticated herd animals like goats, sheep, donkeys, horses and camelids all offer distinct advantages in antibody production. However, their cost of use is often prohibitive, especially where poor antigen response is commonplace; choosing a non-responsive animal can set a research program back or even prevent experiments from moving forward entirely. Over the course of production of antibodies from llamas, we found that some animals consistently produced a higher humoral antibody response than others, even t...
Ortved K, Wagner B, Calcedo R, Wilson J, Schaefer D, Nixon A.Intraarticular (IA) administration of viral vectors expressing a therapeutic transgene is an attractive treatment modality for osteoarthritis (OA) as the joint can be treated as a contained unit. Humoral and cell-mediated immune responses in vivo can limit vector effectiveness. Transduction of articular tissues has been investigated; however, the immune response to IA vectors remains largely unknown. We hypothesized that IA rAAV2 and rAAV5 overexpressing insulin-like growth factor-I (IGF-I) would result in long-term IGF-I formation but would also induce neutralizing antibodies (NAb) and anti-c...
McClellan A, Paterson YZ, Paillot R, Guest DJ.In horses and humans, tendon injuries are a significant problem. Not only can they occur in both athletes and nonathletes, they require lengthy periods of recuperation and undergo poor natural regeneration, which leads to high reinjury rates. Embryonic stem cells (ESCs) may provide a renewable source of allogeneic cells to use in clinical applications to aid tissue regeneration. Equine ESCs can undergo tenocyte differentiation in vivo and in vitro, but the immune properties of tenocytes isolated from either ESCs or tissues have not previously been characterized. Here, we demonstrate that equin...
Roth SP, Burk J, Brehm W, Troillet A.Mesenchymal stromal cells (MSC) represent a promising treatment option for tendon disorders and joint diseases, primarily osteoarthritis. Since MSC are highly context-sensitive to their microenvironment, their therapeutic efficacy is influenced by their tissue-specific pathologically altered targets. These include not only cellular components, such as resident cells and invading immunocompetent cells, but also components of the tissue-characteristic extracellular matrix. Although numerous models have already shown potential MSC-related mechanisms of action in tendon and joint diseases, only a...
Durward-Akhurst SA, Finno CJ, Barnes N, Shivers J, Guo LT, Shelton GD, Valberg SJ.Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. Objective: To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Methods: Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). ...
Murphy BA, Vick MM, Sessions DR, Cook RF, Fitzgerald BP.Peripheral clocks receive timing signals from the master mammalian pacemaker in the suprachiasmatic nucleus (SCN) and function to adaptively anticipate daily changes that influence local physiology. Evidence suggests that peripheral immune activation may act as a resetting signal for circadian clocks in peripheral tissues. We wished to investigate whether acute systemic inflammation could synchronize clock gene expression in equine peripheral blood, a tissue that does not normally oscillate in this species. We report that in vivo administration of lipopolysaccharide (LPS) results in significan...
Smith KC, Whitwell KE, Mumford JA, Hannant D, Blunden AS, Tearle JP.The V592 strain of equid herpesvirus-1 (EHV-1), which was originally isolated from a fetus during an abortion epizootic, has proved to be of low virulence in infection studies. Five Welsh Mountain pony mares and one foal were challenged intranasally or by aerosol with this isolate, and monitored clinically and virologically. All six animals shed virus in nasopharyngeal mucus, and viraemia was recorded from day 7 post-infection (PI). Pathological investigations revealed mild rhinitis and bronchiolitis in the mares, with viral antigen expression in degenerating epithelial cells of the nasal muco...
