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.
Leeth C, Adkins J, Hay A, Bogers S, Potter A, Witonsky S, Zhu J.Immunological studies in the horse are frequently hampered by lack of environmental control, complicated study design, and ethical concerns when performing high risk studies. The purpose of the current study was to investigate the utility of a xenograft model for studying acute equine immune responses. Immunocompromised non obese diabetic (NOD). sudden combined immunodeficiency (scid).gamma-/- (NSG) mice were engrafted with either equine peripheral blood lymphocytes (PBLs) or equine bone marrow to determine an optimal protocol for equine lymphocyte engraftment. We found that both PBL and bone ...
Easton-Jones C.Equid gammaherpesviruses are ubiquitous and widespread in the equine population. Despite their frequent detection, their contribution to immune system modulation and the pathogenesis of several diseases remains unclear. Genetic variability and the combination of equid gammaherpesvirus strains a horse is infected with might be clinically significant. Initial gammaherpesvirus infection occurs in foals peripartum with latency then established in peripheral blood mononuclear cells. A novel EHV-5 study suggests that following inhalation equid gammaherpesviruses might obtain direct access to T and B...
Jørgensen E, Bjarnsholt T, Jacobsen S.In chronic wounds in humans, biofilm formation and wound chronicity are linked, as biofilms contribute to chronic inflammation and delayed healing. Biofilms are aggregates of bacteria, and living as biofilms is the default mode of bacterial life; within these aggregates, the bacteria are protected from both antimicrobial substances and the immune response of the host. In horses, delayed healing is more commonly seen in limb wounds than body wounds. Chronic inflammation and hypoxia are the main characteristics of delayed wound healing in equine limbs, and biofilms might also contribute to this ...
Cassimeris L, Armstrong C, Burger QC, Stokes S, van Eps A, Galantino-Homer H.The euglycemic hyperinsulinemic clamp model (EHC) of equine endocrinopathic laminitis induces rapid loss of lamellar tissue integrity, disrupts keratinocyte functions, and induces inflammation similar to natural disease. Continuous digital hypothermia (CDH) blocks tissue damage in this experimental model, allowing identification of specific genes or molecular pathways contributing to disease initiation or early progression. Archived lamellar tissues (8 horses, 48 h EHC treatment, including CDH-treated front limbs) were used to measure relative expression levels of genes encoding keratin 17 (KR...
Lucassen A, Finkler-Schade C, Schuberth HJ. () fermentation products (SCFP) are used in animal husbandry as pre- and postbiotic feed supplements. A variety of immunomodulatory effects are noted in many species. The purpose of this study was to test the hypothesis that horses fed with SCFP containing feed additive Olimond BB display a modulated early immune response after influenza vaccination. Six horses received Olimond BB pellets (OLI) and five horses were fed placebo pellets (PLA) for 56 days. On day 40 all horses were vaccinated with a recombinant influenza A/equi-2 vaccine. At the day of vaccination, the groups did not differ in t...
Carroll CSE, Andrew ER, Malik L, Elliott KF, Brennan M, Meyer J, Hintze A, Almonte AA, Lappin C, MacPherson P, Schulte KM, Dahlstrom JE, Tamhane R....We describe intratumoral injection of a slow-release emulsion of killed mycobacteria (complete Freund's adjuvant (CFA)) in three preclinical species and in human cancer patients. Efficacy and safety were tested in mammary tumors in mice, in mastocytomas in mice and dogs, and in equine melanomas. In mice, survival, tumor growth, and tumor infiltration by six immune cell subsets (by flow cytometry) were investigated and analyzed using Cox proportional hazards, a random slopes model, and a full factorial model, respectively. Tumor growth and histology were investigated in dogs and horses, as well...
Bannai H, Kambayashi Y, Tsujimura K, Nagashima T, Takebe N, Tominari M, Nemoto M, Ohta M.The antibody response in horses inoculated with 2 doses of a live equine herpesvirus type 1 vaccine with different vaccination intervals (1 to 3 months) was evaluated with regard to the persistence of virus-neutralizing (VN) antibodies. The durations for which the geometric mean VN titers were maintained significantly higher than those before the first vaccination (P<0.05) were up to 5 months in horses that received the vaccination with a 1-month interval (n=17) and 7 months for those that received it with a 2-month (n=17) or 3-month interval (n=14 or 17). The vaccination program with the 2...
Skipper L, Pusterla N.The purpose of this study was to establish if peak serum amyloid A (SAA) concentrations can be used to determine an appropriate immune response to a vaccine containing West Nile Virus (WNV) antigen. A pilot study with 20 clinically healthy horses was performed to identify peak SAA concentration postvaccination with a commercial multivalent WNV vaccine. Blood was collected for SAA at 0, 24, 48, 72, 96, 168 hours postvaccination. Serum for WNV serum neutralization antibody testing was obtained immediately prior to and 30 days postvaccination. An additional 40 horses underwent the study protocol,...
Zaugg I, Ottiger HP.The aim of the vigilance system in Switzerland is the evaluation and classification of reported suspected adverse reactions of immunological veterinary medicines (IVMP), including suspected lack of expected efficacy. The Institute of Virology and Immunology (IVI) is the competent authority for marketing authorizations of immunological veterinary medicinal products in Switzerland and responsible for the vaccinovigilance system. In 2020, 130 adverse reaction reports were received (5% less compared to 2019). The reports mainly concerned dogs (41%) and cats (25%) followed by cattle (18%) and horse...
Vail KJ, da Silveira BP, Bell SL, Cohen ND, Bordin AI, Patrick KL, Watson RO.Rhodococcus equi is a major cause of foal pneumonia and an opportunistic pathogen in immunocompromised humans. While alveolar macrophages constitute the primary replicative niche for R. equi, little is known about how intracellular R. equi is sensed by macrophages. Here, we discovered that in addition to previously characterized pro-inflammatory cytokines (e.g., Tnfa, Il6, Il1b), macrophages infected with R. equi induce a robust type I IFN response, including Ifnb and interferon-stimulated genes (ISGs), similar to the evolutionarily related pathogen, Mycobacterium tuberculosis. Follow up studi...
Hay AN, Potter A, Lindsay D, LeRoith T, Zhu J, Cashwell S, Witonsky S, Leeth C.Sarcocystis neurona is the predominant etiological agent of the infectious equine neurologic disease, equine protozoal myeloencephalitis (EPM), which is prevalent in the United States. A wealth of knowledge about S. neurona biology and its life cycle has accumulated over the last several decades. However, much remains unknown about the aberrant equine host's immune response to S. neurona and the relatively high prevalence of exposure to the protozoa but relatively infrequent occurrence of clinical neurologic disease. Mouse models simulating EPM are commonly used to study the disease due to num...
Kahn SK, Cywes-Bentley C, Blodgett GP, Canaday NM, Turner-Garcia CE, Vinacur M, Cortez-Ramirez SC, Sutter PJ, Meyer SC, Bordin AI, Vlock DR, Pier GB....The efficacy of transfusion with hyperimmune plasma (HIP) for preventing pneumonia caused by Rhodococcus equi remains ill-defined. Quarter Horse foals at 2 large breeding farms were randomly assigned to be transfused with 2 L of HIP from adult donors hyperimmunized either with R. equi (RE HIP) or a conjugate vaccine eliciting antibody to the surface polysaccharide β-1→6-poly-N-acetyl glucosamine (PNAG HIP) within 24 hours of birth. Antibody activities against PNAG and the rhodococcal virulence-associated protein A (VapA), and to deposition of complement component 1q (C՛1q) onto PNAG were d...
Bantle CM, Rocha SM, French CT, Phillips AT, Tran K, Olson KE, Bass TA, Aboellail T, Smeyne RJ, Tjalkens RB.Viral infection of the central nervous system (CNS) can cause lasting neurological decline in surviving patients and can present with symptoms resembling Parkinson's disease (PD). The mechanisms underlying postencephalitic parkinsonism remain unclear but are thought to involve increased innate inflammatory signaling in glial cells, resulting in persistent neuroinflammation. We therefore studied the role of glial cells in regulating neuropathology in postencephalitic parkinsonism by studying the involvement of astrocytes in loss of dopaminergic neurons and aggregation of α-synuclein protein fo...
Oladunni FS, Oseni SO, Martinez-Sobrido L, Chambers TM.Equine influenza virus (EIV) is a constantly evolving viral pathogen that is responsible for yearly outbreaks of respiratory disease in horses termed equine influenza (EI). There is currently no evidence of circulation of the original H7N7 strain of EIV worldwide; however, the EIV H3N8 strain, which was first isolated in the early 1960s, remains a major threat to most of the world's horse populations. It can also infect dogs. The ability of EIV to constantly accumulate mutations in its antibody-binding sites enables it to evade host protective immunity, making it a successful viral pathogen. C...
Miller AB, Harris PA, Barker VD, Adams AA.Long-distance transport is associated with stress-related changes in equine immune function, and shipping-associated illnesses are often reported. Horses are frequently transported short distances, yet the effects of short-term transport on immune function remain largely unknown. Twelve horses, aged 15-30 yr, were assigned to either the control (n = 6) or treatment (n = 6) groups; treatment horses received a daily antioxidant supplement 3 weeks before and after transport. All horses were transported for approximately 1.5-2 hr on Day 0. Blood was collected via jugular venipuncture at 15-min pre...
Hu D, Yang J, Qi Y, Li B, Li K, Mok KM.Intestinal microbiota is involved in immune response and metabolism of the host. The frequent use of anthelmintic compounds for parasite expulsion causes disturbance to the equine intestinal microbiota. However, most studies were on the effects of such treatment on the intestinal bacterial microbes; none is on the entire microbial community including archaea and eukaryotic and viral community in equine animals. This study is the first to explore the differences of the microbial community composition and structure in Przewalski's horses prior to and following anthelmintic treatment, and to dete...
Fettelschoss-Gabriel A, Birkmann K, Pantelyushin S, Kündig TM.Equine Culicoides hypersensitivity (CH) is the most common allergic condition in horses affecting the skin. This review focuses on immunopathology and molecular mechanisms of equine CH. The role of eosinophils is emphasized, as well as disease severity and the influence of long-term chronic allergen exposure on T helper (Th) 2 cells. Using current knowledge from human allergic disorders, similar effects are hypothesized in equine patients. Key aspects of CH diagnosis and treatment are discussed, focusing on allergen specific immunotherapy and allergen-independent approaches, such as targeting ...
Freitas NFQR, Otaka DY, Galvão CC, de Almeida DM, Ferreira MRA, Moreira Júnior C, Hidalgo MMMH, Conceição FR, Salvarani FM.In horses, Clostridium perfringens is associated with acute and fatal enterocolitis, which is caused by a beta toxin (CPB), and myonecrosis, which is caused by an alpha toxin (CPA). Although the most effective way to prevent these diseases is through vaccination, specific clostridial vaccines for horses against C. perfringens are not widely available. The aim of this study was to pioneer the immunization of horses with three different concentrations (100, 200 and 400 µg) of C. perfringens recombinant alpha (rCPA) and beta (rCPB) proteins, as well as to evaluate the humoral immune response ove...
Van Hecke L, Magri C, Duchateau L, Beerts C, Geburek F, Suls M, Da Dalt L, Patruno M, Saunders J, Broeckx SY, Depuydt E, Spaas JH.The use of mesenchymal stem cells (MSCs) for the treatment of equine joint disease is widely investigated because of their regenerative and immunomodulatory potential. Allogeneic MSCs provide a promising alternative to autologous MSCs, since the former are immediately available and enable a thorough donor screening. However, questions have been raised concerning the immunogenic potential of allogeneic MSCs, especially after repeated administration. Methods: Current retrospective study assessed the cellular and humoral immunogenicity of ten jumping and dressage horses with naturally occurring d...
Cohen ND, Kahn SK, Cywes-Bentley C, Ramirez-Cortez S, Schuckert AE, Vinacur M, Bordin AI, Pier GB.Rhodococcus equi is a prevalent cause of pneumonia in foals worldwide. Our laboratory has demonstrated that vaccination against the surface polysaccharide β-1→6-poly-N-acetylglucosamine (PNAG) protects foals against intrabronchial infection with R. equi when challenged at age 28 days. However, it is important that the efficacy of this vaccine be evaluated in foals when they are infected at an earlier age, because foals are naturally exposed to virulent R. equi in their environment from birth and because susceptibility is inversely related to age in foals. Using a randomized, blind experim...
Santos AC, Nogueira CEW, Dos Santos Suñe Moraes B, Müller V, Mousquer MA, Leite FPL.Equine theileriosis, caused by the Theileria equi protozoan, is a disease of worldwide importance. T. equi expresses surface proteins, of which the EMA-2 protein is a promising antigen for vaccine use. The aim of this study was to evaluate the immune response of adult horses, pregnant mares, and foals to an experimental EMA-2 protein of recombinant T. equi vaccine. A total of 46 horses were used in this study for vaccine trials and challenges. Twelve geldings, 14 pregnant mares, and 14 foals were divided into vaccinated and control groups. Total serum specific anti-rEMA-2 IgG, IgG subclasses, ...
Pusterla N, James K, Bain F, Barnett DC, Chappell D, Gaughan E, Craig B, Schneider C, Vaala W, Papich M.The aim of this study was to determine if bi-weekly administration of diclazuril at half the label dose would reduce seroprevalence and magnitude of titers to S. neurona in healthy horses naturally exposed to the apicomplexan protozoal parasite. 12 healthy adult horses were moved from a low-risk exposure to a farm with high exposure rate to S. neurona in their horse population. The horses were randomly assigned to either a treatment or a control group. Treatment consisted in the administration of half the label dose (0.5 mg/kg) of diclazuril (Protazil) pelleted top dress twice weekly (every 3-...
Warda FF, Ahmed HES, Shafik NG, Mikhael CA, Abd-ElAziz HMG, Mohammed WA, Shosha EA.Equine herpesvirus-1 infection in horses causes a wide range of manifestations affecting the respiratory tract. The virus can cause serious economic losses through sporadic abortion in pregnant mares, perinatal death, respiratory disease in young foals. This study was designed to prepare inactivated equine herpesvirus-1 (EHV-1) vaccine using both 0.005 M binary ethylenimine (BEI) and 0.0006% formaldehyde (FA) to decrease the use of BEI and provide a good immunological response. The efficacy, safety, and duration of immunity of the prepared inactivated EHV-1 vaccine were evaluated. Methods: The...
Equine asthma is an inflammatory respiratory disorder, classified as mild-moderate (MEA) and severe (SEA). SEA is characterized by recurrent exacerbations, consisting of dyspnea, coughing and exercise intolerance; MEA causes poor performance, occasional cough and mucus hypersecretion. Although a precise pathogenesis is not completely understood, allergic mechanisms are considered an important pathophysiological feature of equine asthma. In equine medicine, intradermal testing (IDT) is effective in identifying hypersensitivity to specific allergens. However, to date, the studies about IDT in as...
El-Sheikh Ali H, Loux SC, Kennedy L, Scoggin KE, Dini P, Fedorka CE, Kalbfleisch TS, Esteller-Vico A, Horohov DW, Erol E, Carter CN, Smith JL, Ball BA.Nocardioform placentitis (NP) continues to result in episodic outbreaks of abortion and preterm birth in mares and remains a poorly understood disease. The objective of this study was to characterize the transcriptome of the chorioallantois (CA) of mares with NP. The CA were collected from mares with confirmed NP based upon histopathology, microbiological culture and PCR for Amycolatopsis spp. Samples were collected from the margin of the NP lesion (NPL, n = 4) and grossly normal region (NPN, n = 4). Additionally, CA samples were collected from normal postpartum mares (Control; CRL, n...
Monteiro de Barros MR, Davies-Morel MCG, Mur LAJ, Creevey CJ, Alison RH, Nash DM.Persistent mating-induced endometritis is a major cause of poor fertility rates in the mare. Endometritis can be investigated using an ex vivo equine endometrial explant system which measures uterine inflammation using prostaglandin F2α as a biomarker. However, this model has yet to undergo a wide-ranging assessment through transcriptomics. In this study, we assessed the transcriptomes of cultured endometrial explants and the optimal temporal window for their use. Endometrium harvested immediately post-mortem from native pony mares (n = 8) were sampled (0 h) and tissue explants were cultured ...
Jonsdottir S, Torsteinsdottir S, Svansson V, Gudbrandsson J, Stefansdottir SB, Mar Bjornsson J, Runarsdottir A, Marti E.Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses, an IgE-mediated reaction to Culicoides midges. Causative Culicoides spp. are not indigenous in Iceland resulting in high prevalence of IBH in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. The aims were (i) to compare IgE levels in sera of IBH-affected horses born in Iceland (n = 47) with horses of the Icelandic breed (n = 23) and of other breeds (n = 27) born in Culicoides infested area; (ii) to investigate if barley could be a useful production system of allerge...
Barrett RS, Wiethoelter A, Halpin K.To elucidate veterinarians' and horse owners' perceptions towards the use of Hendra virus (HeV) antibody titre testing and how it influences veterinary advice. Methods: Six semi-structured phone interviews were conducted with veterinarians who have submitted samples for HeV antibody titre testing. Interviews were recorded, transcribed and thematically analysed to identify and report common themes within the data. Results: Veterinarians are predominantly using the titre tests as an alternative to vaccination due to clients' fear of vaccine reactions. The high cost of titre testing, the difficul...
Tomlinson JE, Wolfisberg R, Fahnøe U, Patel RS, Trivedi S, Kumar A, Sharma H, Nielsen L, McDonough SP, Bukh J, Tennant BC, Kapoor A, Rosenberg BR....Equine hepacivirus (EqHV) is phylogenetically the closest relative of HCV and shares genome organization, hepatotropism, transient or persistent infection outcome, and the ability to cause hepatitis. Thus, EqHV studies are important to understand equine liver disease and further as an outbred surrogate animal model for HCV pathogenesis and protective immune responses. Here, we aimed to characterize the course of EqHV infection and associated protective immune responses. Seven horses were experimentally inoculated with EqHV, monitored for 6 months, and rechallenged with the same and, subsequen...
Wagner B, Burton A, Ainsworth D.Cytokines produced by T helper (Th) cells are important in orchestrating the immune response during health and disease. Recent reports indicated that cytokine mRNA expression in foals is often quantitatively lower than that of adult horses suggesting that foal T cells are not fully mature. Here, peripheral blood mononuclear cells from foals and adult horses were stimulated with phorbol 12-myristate 13-acetate and analyzed for intracellular interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and IL-10 production, representing the Th1, Th2 and regulatory TR1 cell phenotypes respectively, by flow ...
Edlund Toulemonde C, Daly J, Sindle T, Guigal PM, Audonnet JC, Minke JM.Fifteen influenza-naive Welsh mountain ponies were randomly assigned to three groups of five. A single dose of a recombinant ALVAC vaccine was administered intramuscularly to five of the ponies, two doses, administered five weeks apart, were administered to five, and the other five served as unvaccinated, challenge controls. Two weeks after the completion of the vaccination programme, the ponies were all challenged by exposure to an aerosol of influenza virus A/eq/Newmarket/5/03. Their clinical signs were scored daily for 14 days according to a standardised scoring protocol, and nasal swabs we...
Stoneham SJ, Palmer L, Cash R, Rossdale PD.This paper describes the use of a latex agglutination assay to measure serum amyloid A (SAA) in the neonatal foal. The normal range and response to clinical disease was determined. This retrospective study evaluated SAA concentrations over the first 3 days postpartum of 226 Thoroughbred foals judged to be clinically healthy. The normal range for each day was determined; levels were found to be significantly highest on Day 2 (Day 1 vs. Day 2 P<0.0001). The 95th percentile for Days 1-3 was 27.1 mg/l. Clinical records of 133 foals, presented as first or second opinion cases, were evaluated. Fo...
Murcia RY, Vargas A, Lavoie JP.Glucocorticoids (GCs) are the most effective drugs for the treatment of human asthma. However, a subgroup of asthmatic patients with neutrophilic airway inflammation is insensitive to GCs. Interleukin-17 (IL-17), a cytokine upregulated in the airways of a subset of human asthmatic patients, contributes to the recruitment of neutrophils and induces a glucocorticoid resistance in human airway epithelial cells. We hypothesized that IL-17 similarly activates neutrophils and contributes to their persistence in the asthmatic airways in spite of glucocorticoid therapy. To determine whether IL-17 dire...
Viļuma A, Mikko S, Hahn D, Skow L, Andersson G, Bergström TF.The mammalian Major Histocompatibility Complex (MHC) region contains several gene families characterized by highly polymorphic loci with extensive nucleotide diversity, copy number variation of paralogous genes, and long repetitive sequences. This structural complexity has made it difficult to construct a reliable reference sequence of the horse MHC region. In this study, we used long-read single molecule, real-time (SMRT) sequencing technology from Pacific Biosciences (PacBio) to sequence eight Bacterial Artificial Chromosome (BAC) clones spanning the horse MHC class II region. The final asse...
Prow NA, Tan CS, Wang W, Hobson-Peters J, Kidd L, Barton A, Wright J, Hall RA, Bielefeldt-Ohmann H.In 2011 an unprecedented epidemic of equine encephalitis occurred in south-eastern (SE) Australia following heavy rainfall and severe flooding in the preceding 2-4 months. Less than 6% of the documented cases occurred in Queensland, prompting the question of pre-existing immunity in Queensland horses. A small-scale serological survey was conducted on horses residing in one of the severely flood-affected areas of SE-Queensland. Using a flavivirus-specific blocking-ELISA we found that 63% (39/62) of horses older than 3 years were positive for flavivirus antibodies, and of these 18% (7/38) had ne...
Craigo JK, Li F, Steckbeck JD, Durkin S, Howe L, Cook SJ, Issel C, Montelaro RC.Among the diverse experimental vaccines evaluated in various animal lentivirus models, live attenuated vaccines have proven to be the most effective, thus providing an important model for examining critical immune correlates of protective vaccine immunity. We previously reported that an experimental live attenuated vaccine for equine infectious anemia virus (EIAV), based on mutation of the viral S2 accessory gene, elicited protection from detectable infection by virulent virus challenge (F. Li et al., J. Virol. 77:7244-7253, 2003). To better understand the critical components of EIAV vaccine e...
Ambagala APN, Gopinath RS, Srikumaran S.Equine herpesvirus-1 (EHV-1) downregulates surface expression of major histocompatibility complex (MHC) class I molecules on infected cells. The objective of this study was to investigate whether EHV-1 interferes with peptide translocation by the transporter associated with antigen processing (TAP) and to identify the proteins responsible. Using an in vitro transport assay, we showed that EHV-1 inhibited transport of peptides by TAP as early as 2 h post-infection (p.i). Complete shutdown of peptide transport was observed by 8 h p.i. Furthermore, pulse-chase experiments revealed that maturation...
Burton AB, Wagner B, Erb HN, Ainsworth DM.Previously it was reported that compared to surviving septic foals, non-surviving foals had a 35-fold increase in interleukin-10 (IL-10) and 15-fold increase in IL-6 gene expression in their peripheral blood mononuclear cells (PBMC). As gene expression profiles can be time-consuming, we sought to determine if serum IL-6 and IL-10 in foals would aid in the diagnosis and prognosis of septicemia. A prospective study of septic neonatal foals admitted to the Cornell University Equine Hospital during 2007 and 2008 was performed. Septicemia was confirmed in 15 foals using blood culture results and se...
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...
Soboll G, Horohov DW, Aldridge BM, Olsen CW, McGregor MW, Drape RJ, Macklin MD, Swain WF, Lunn DP.We have previously demonstrated that hemagglutinin (HA) gene vaccination and influenza virus infection generate protective antibody responses in equids. However, these antibody responses differ substantially in that particle mediated DNA vaccination does not induce an immunoglobulin A (IgA) response. A study was performed to investigate the regional immunoregulatory mechanisms associated with these different immune responses. Ponies were either vaccinated with equine HA DNA vaccines at skin and mucosal sites, infected with influenza virus or left untreated and influenza-specific antibody respo...
Wong DM, Wilkins PA.Defining and describing the systemic inflammatory response syndrome (SIRS) and sepsis facilitated recognition and investigation of the complex disease processes involving the host response to infection and trauma. Over the years a variety of definitions of SIRS have been examined and applied to numerous research studies to improve critical care in both human and veterinary clinical practice. This article summarizes the history of the development of the SIRS definition, outlines the pathophysiologic processes that are involved in SIRS, and provides a specific definition for use in foal medicine...
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...
Kleiber C, McGorum BC, Horohov DW, Pirie RS, Zurbriggen A, Straub R.Equine recurrent airway obstruction (RAO) is thought to result from an aberrant immune response to inhaled antigens, modulated by T lymphocytes via the secretion of pro-inflammatory cytokines. However data relating to the phenotypes of the T lymphocytes present in peripheral blood and bronchoalveolar lavage fluid of RAO horses and their cytokine profiles are contradictory. The aim of this study was to further investigate the cytokine (IL-4, IL-5, IL-13 and INF-gamma) mRNA expression profile in peripheral blood lymphocytes and bronchoalveolar lavage lymphocytes from RAO and control horses, befo...
Sellon DC.The ability of EIAV to persistently infect horses in the face of a profound immune response by the host makes it a potentially devastating disease for the horse population of the United States. Its ability to evade host immune defenses by lying dormant in apparently healthy animals and by rapidly changing its antigenic determinants is proving to be a major obstacle to vaccine development. Because most infected horses appear clinically normal and a large proportion of horses in this country remain untested, the virus is not likely to be eradicated in the near future. Yet, for the same reason, b...
Wagner B, Hillegas JM, Antczak DF.Interleukin-4 (IL-4) is secreted by T helper type 2 cells, mast cells, basophils and eosinophils. Detection of IL-4 can contribute the evaluation of cellular immune responses during infectious diseases, immunological disorders or vaccination. We used recombinant equine IL-4 to generate a monoclonal antibody (mAb) to equine IL-4. The mAb detected recombinant IL-4 in mammalian cells transfected with different plasmids containing IL-4 cDNA. After mitogen stimulation of equine peripheral blood mononuclear cells, an intracellular protein was recognized by the new mAb in 1-2% of lymphocytes using fl...
Nash DM, Sheldon IM, Herath S, Lane EA.Reproductive efficiency in mares is low and persistent mating-induced endometritis (PMIE) is an important cause of subfertility. Mating-induced endometritis (MIE) an obligate precursor to PMIE, is a ubiquitous, transient inflammatory response to the presence of sperm, seminal components and pathogens. However, the specific inflammatory pathways that derive from MIE and that may also be precursors to PMIE are not clear. The ability to identify and measure robust, repeatable markers of inflammation integral to MIE may be key to understanding the progression to PMIE. The aim of the study was to (...
Miró J, Marín H, Catalán J, Papas M, Gacem S, Yeste M.In the donkey, artificial insemination (AI) with frozen-thawed semen is associated with low fertility rates, which could be partially augmented through adding seminal plasma (SP) and increasing sperm concentration. On the other hand, post-AI endometrial inflammation in the jenny is significantly higher than in the mare. While previous studies analyzed this response through recovering Polymorphonuclear Neutrophils (PMN) from uterine washings, successive lavages can detrimentally impact the endometrium, leading to fertility issues. For this reason, the first set of experiments in this work inten...
Robinson C, Waller AS, Frykberg L, Flock M, Zachrisson O, Guss B, Flock JI.The equine disease strangles, caused by Streptococcus equi, remains a major cause of welfare and economic cost to the global horse industry. Here we report the safety, immunogenicity and efficacy of a novel multi-component chimeric fusion protein vaccine, called Strangvac, when administered to ponies via the intramuscular route. Across the four studies, Strangvac was safe and induced robust antibody responses towards the vaccine components in blood serum and the nasopharynx, which were boosted by revaccination up to 12 months after a primary course of 2 vaccinations 4 weeks apart. The vaccin...
Goodyear A, Troyer R, Bielefeldt-Ohmann H, Dow S.The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effec...
Karagianni AE, Lisowski ZM, Hume DA, Scott Pirie R.The mononuclear phagocyte system (MPS) is a family of cells of related function that includes bone marrow progenitors, blood monocytes and resident tissue macrophages. Macrophages are effector cells in both innate and acquired immunity. They are a major resident cell population in every organ and their numbers increase in response to proinflammatory stimuli. Their function is highly regulated by a wide range of agonists, including lymphokines, cytokines and products of microorganisms. Macrophage biology has been studied most extensively in mice, yet direct comparisons of rodent and human macro...
Jacobs CC, Holcombe SJ, Cook VL, Gandy JC, Hauptman JG, Sordillo LM.Endotoxaemia contributes to morbidity and mortality in horses with colic due to inflammatory cascade activation. Effective therapeutic interventions are limited for these horses. Ethyl pyruvate (EP), an anti-inflammatory agent that alters the expression of proinflammatory cytokines, improved survival and organ function in sepsis and gastrointestinal injury in rodents and swine. Therapeutic efficacy of EP is unknown in endotoxaemic horses. Objective: Determine the effects of EP on signs of endotoxaemia and expression of proinflammatory cytokines following administration of lipopolysaccharide (L...
Canisso IF, Ball BA, Cray C, Williams NM, Scoggin KE, Davolli GM, Squires EL, Troedsson MH.Currently, placentitis, an important cause of late pregnancy loss in mares, is diagnosed by clinical signs and ultrasonography. Acute phase proteins (APP) are mainly produced and secreted by the liver in response to acute inflammatory stimuli. We hypothesized that APP are increased in mares with placentitis. Methods: Concentrations of serum amyloid A (SAA), haptoglobin (Hp), fibrinogen (Fb), and white blood cell counts (WBC) were determined in plasma of mares with experimentally induced placentitis and gestationally age-matched control mares. Placentitis was induced via intracervical inoculati...
Belknap JK, Giguère S, Pettigrew A, Cochran AM, Van Eps AW, Pollitt CC.Recent research has indicated that inflammation plays a role in the early stages of laminitis and that, similar to organ failure in human sepsis, early inflammatory mechanisms may lead to downstream events resulting in lamellar failure. Characterisation of the type of immune response (i.e. innate vs. adaptive) is essential in order to develop therapeutic strategies to counteract these deleterious events. Objective: To quantitate gene expression of pro-inflammatory cytokines known to be important in the innate and adaptive immune response during the early stages of laminitis, using both the bla...
Hooper-McGrevy KE, Wilkie BN, Prescott JF.Rhodococcus equi causes severe pyogranulomatous pneumonia in foals and in immunocompromised humans. Replication of virulent isolates within macrophages correlates with the presence of a large plasmid which encodes a family of seven virulence-associated proteins (VapA and VapC to VapH), whose functions are unknown. Although cell-mediated immunity is thought to be crucial in eliminating R. equi infection, antibody partially protects foals. The antibody response to both VapA and VapC was similar in six adult horses and six naturally exposed but healthy foals, as well as in eight foals with R. equ...
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...
Capomaccio S, Cappelli K, Barrey E, Felicetti M, Silvestrelli M, Verini-Supplizi A.It is known that moderate physical activity may have beneficial effects on health, whereas strenuous effort induces a state resembling inflammation. The molecular mechanisms underlying the cellular response to exercise remain unclear, although it is clear that the immune system plays a key role. It has been hypothesized that the physio-pathological condition that develops in athletes subjected to heavy training is caused by derangement of cellular immune regulation. The purpose of the present study was to obtain information on endurance horse gene transcription under strenuous conditions and t...
Walton TE, Alvarez O, Buckwalter RM, Johnson KM.Ten horses (Equus caballus) were vaccinated with strain TC-83 Venezuelan equine encephalomyelitis (VEE) virus vaccine. Febrile responses and leukopenia due to a reduction of lymphocytes and neutrophils were observed in all animals. Viremias were demonstrable in eight horses, with a maximum of 10(3.5) median tissue culture infectious dose units per ml of serum in two horses. Clinical illness with depression and anorexia were observed in five horses. Neutralizing (N), hemagglutination-inhibiting, and complement-fixing antibodies to the vaccine virus were demonstrable by 5, 6.5, and 7 days, respe...
Timoney JF, Kumar P.Little is known about entry and subsequent multiplication of Streptococcus equi following exposure of a susceptible horse. This information would have value in design of intranasal vaccines and understanding of shedding and protective immune responses. Objective: To determine entry points and sites of subsequent replication and dispersion of S. equi at different times after intranasal infection or commingling exposure. Methods: Previously unexposed horses and ponies were subjected to euthanasia 1, 3, 20 or 48 h following intranasal inoculation with biotin labelled or unlabelled S. equi CF32. S...
Tumas DB, Hines MT, Perryman LE, Davis WC, McGuire TC.The immune control of chronic equine infectious anaemia (EIA) lentiviral infection was investigated by specifically depleting CD5+ T lymphocytes in vivo with monoclonal antibody (MAb) or by immunosuppression with corticosteroids. MAb was given at 25 to 50 mg/day intravenously for 11 days. Murine IgG1 anti-equine CD2 MAb (n = 2 horses) or IgG1 (n = 2) and IgG2a control MAb (n = 2 normal; 2 EIA-infected) did not deplete CD2+ T lymphocytes in horses. Horses given murine IgG2a anti-CD5 MAb HB19A (n = 4 normal; 5 EIA-infected) had depletion of peripheral blood CD5+ T lymphocytes during treatment. T...
