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.
Li Z, Yu T, Ge L, Lv S, Fu Q, Shi H.Equine herpesvirus type 1 (EHV-1) is a major veterinary pathogen causing significant economic losses in the livestock industry. Despite its impact, effective vaccines and targeted antiviral strategies remain limited, largely due to an incomplete understanding of host factors regulating viral replication and pathogenesis. Unassigned: To systematically identify host genes essential for EHV-1 infection, we established a BHK-21 cell line stably expressing Cas9 and performed a genome-wide CRISPR/Cas9 knockout screen using a pooled lentiviral single-guide RNA library. Significantly enriched candidat...
Dropsy H, Husson JC, Degorce-Rubiales F, Cochet-Faivre N.A 9-year-old gelding Quarter Horse with a lesion on the right upper eyelid was diagnosed with cutaneous lupus erythematosus. Clinical resolution and control of UV-induced flares were achieved with topical tacrolimus and a UV-blocking mask without adverse effects over the following 3 years.
Aucoin AA, Zhidkov V, Legere RM, Borba KER, Landrock KK, Parker LE, Bray JM, Bordin AI, Cohen ND.To characterize age-related trajectories of the relative concentrations of anti-virulence-associated protein A (VapA) immunoglobulin (Ig)-G1, IgG3/5, IgG4/7, and IgA in serum and bronchoalveolar lavage fluid (BALF) as indicators of systemic and intrapulmonary immune responses in foals naturally exposed to Rhodococcus equi. Unassigned: Blood and BALF samples were collected at ages 4, 14, 28, and 56 days from healthy Quarter Horse foals (n = 19) naturally exposed to R equi. Samples were tested via ELISA for relative concentration of IgG1, IgG3/5, IgG4/7, and IgA recognizing the VapA of R equi. D...
Schmitz M, Neugebauer E, Full F, Conn KL.Comparative transcriptomics offers a powerful approach to elucidate host-virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species' cells infected with three alphaherpesviruses-herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)-to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection...
Carotenuto SE, Broussard G, Fox GA, Hayes WK.To assess the efficacy of a new equine F[ab'] antivenom (US Department of Agriculture code 6101.05) in removing serum venom and lowering the snakebite severity score (SSS) in animals suffering from naturally occurring viperid envenomation. Methods: Retrospective study, April 2020 to October 2021. Methods: Veterinary hospitals across four North American regions. Methods: Twenty-two dogs, one cat, and one horse. Methods: All patients received the new antivenom intravenously and were assessed for clinical response. Most dogs required one vial for clinical control of signs. Results: Among the dogs...
Pettersson J, Levanov L, Tervo S, Hautala K, Aaltonen K, Utriainen M, Kareinen L, Gadd T, Sironen T, Vapalahti O, Kinnunen PM.Parapoxviruses (PPV) cause skin and mucous membrane signs to several animal species and humans worldwide. Equine parapoxvirus (EqPPV) was first detected in a sick horse in Finland in 2013. It is potentially zoonotic, and a similar virus has been detected in humans in the USA. In winter 2021–2022, EqPPV caused a large-scale pastern dermatitis epidemic in racehorses all over Finland. Field reports suggest that similar epidemics of unverified cause have also occurred in 2015 and 2019. The aim of this study was to develop a serological test and study the immune response, seroprevalence, and hist...
Heilen LB, Roßgardt J, Dern-Wieloch J, Vogelsberg J, Staszyk C.Horses' hypsodont (high-crowned) teeth face permanent dental wear. This is compensated for by a continuous eruption, which requires a high adaptability of odontoblasts; otherwise, the dental pulp would be exposed. Here, we report on how equine odontoblasts respond to the challenge of maintaining a high production rate of dentin. We analyzed CD90, a marker of odontoblastic differentiation, and nestin, a marker of mature odontoblasts, in equine pulpal tissue via immunofluorescence. For comparison, we examined the hypselodont (ever-growing) incisors and brachydont (short-crowned) molars of rats. ...
Richardson LM, Gordon J, Davila C, Chamoun-Emanuelli AM, Zdyrski C, Whitfield-Cargile CM.Gastrointestinal (GI) disease is a major cause of morbidity and mortality in horses, with disruption of the intestinal epithelial barrier playing a central role in disease pathogenesis. A deeper understanding of the molecular and functional properties of the equine intestinal barrier is essential to improve diagnostics and therapeutics. While intestinal organoids have emerged as a promising tool for modeling GI physiology and disease, equine-specific data remain limited. Existing studies vary in methodology and often lack functional characterization, particularly across different intestinal re...
Thieulent CJ, Sarkar S, Carossino M, Bhowmik M, Zhu H, Balasuriya UBR.Our laboratory identified the susceptible allelic variant of equine CXCL16 protein (EqCXCL16S) as an entry receptor for equine arteritis virus (EAV). However, EAV has a broad host cell tropism and infects cells that lack EqCXCL16S. Thus, we hypothesized that EAV interacts with other host cell protein(s) that facilitate EAV infection. A virus overlay protein-binding assay in combination with a Far-Western blot from EAV-susceptible equine pulmonary artery endothelial cells (EECs) and equine dermal fibroblasts (E. Derm) identified a 57 kDa protein, present in the membrane fraction of the protein ...
Beniwal N, Lal B, Mithina S, Verma CK, Kumar S, Phagna V, Jakhar K, Sonar S, Gupta V, Singh R, Kumar N, Tan CW, Thachamvally R, Singha H, Murzello K....Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission ...
Kern-Allely C, Scott D, Magzamen S, Duncan C.Air pollution is a major global health threat that is expected to worsen, yet its effects on domestic animals remain poorly understood. The objective of this scoping review was to synthesize existing evidence on associations between ambient air pollutants and health outcomes in domestic animals and to identify gaps to guide future research. Unassigned: A scoping review was conducted following the Arksey and O'Malley framework and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines with 2 search databases (PubMed and Web of Science) using ...
Shahid MA, Guitart AS, Bertin FR, Simon O, Ceusters J, Serteyn D, Whitworth DJ.A minimally invasive microbiopsy-based method for the isolation of mesenchymal stem cells (MSCs) from equine skeletal muscle (M-MSCs) provides a readily accessible source of MSCs for clinical applications. We examined the expression of genes associated with immunomodulation and anti-inflammatory pathways, in addition to those of growth factors and the major histocompatibility complex (MHC) molecules I and II, at constitutive levels and after priming with inflammatory cytokines, an immunostimulant, and heat-shocking. While there was notable variation between the M-MSCs from each of the horses i...
Varela V, Costa M, Maciel C, Barbeito J, Barrera EE, Gutierre E, Correa A, Elgue M, Carrasco S, Larrosa MD, Pereira M, Correa J, Crosignani N....Anti-NGF monoclonal antibodies have recently been approved for treating degenerative joint disease, including osteoarthritis pain, in dogs and cats. However, their widespread use is limited by high cost and the requirement for repeated injections. Nerve Growth Factor and Substance P play central roles in the initiation and maintenance of inflammation and chronic pain in OA. There is a pressing need for new, safe, cost-effective therapies that target the underlying mechanisms of OA chronic pain. Here, we designed and produced a novel recombinant fusion protein, termed rNGFSP, which functions as...
Kirmse L, Thieme K, Doherr MG, Eule JC.To evaluate different laboratory procedures for determining the etiologic diagnosis of equine recurrent uveitis regarding intraocular infection with Leptospira spp. and to establish a diagnostic guideline. Methods: Eighty horses with a history of ERU were ophthalmologically examined. Serum and aqueous humor were collected. Total protein, albumin level, and MAT against Leptospira spp. were evaluated on serum and aqueous humor. PCR for Leptospira spp., EHV-1 and -4 was performed on aqueous humor. Goldmann-Witmer coefficient (GWC) and C-value (CC) were calculated based on MAT. In 42 cases, an add...
Qiu Y, Lei Y, Yi X, Tang X, Zhang B, Wang S, Sun X.This study investigated three donkey breeds-Guanzhong, Jiami, and Northern Shaanxi-to characterize the structural organization and diversification mechanisms of the immunoglobulin light-chain (IgL) loci and to conduct both intra-breed and interspecies comparisons with horses. The donkey IGλ locus is located on chromosome 8 and arranged in a Vλ-(Jλ-Cλ)-Vλ configuration. It contains 7 Cλ genes, each preceded by a corresponding Jλ gene to form a Jλ-Cλ cluster. Upstream of this cluster, 156 Vλ genes were identified, including 29 potential functional genes; downstream, 98 Vλ genes were d...
Murillo A, Lebrero ME, Valdés M, Ramos J, Villanueva-Saz S, Davies JE, Gómez Á, Pérez E, Riera C, Marteles-Aragüés D.Equine leishmaniosis, caused by Leishmania infantum and transmitted by infected sand flies, has been increasingly reported in Europe, although clinical and immunological data remain scarce. We describe a 10-year-old mare from southern Spain presenting with periocular nodular lesions. Histopathology and immunohistochemistry confirmed granulomatous dermatitis with intrahistiocytic Leishmania amastigotes. Additionally, Leishmania infantum DNA was detected in paraffin embedded skin biopsy. Following surgical removal of the lesions, sequential serological monitoring using enzyme-linked immunosorben...
Sayre KC, Flores-Ahlschwede P, Wethington AB, Kahn SK, Bray JM, Volding DM, Ahlschwede S, Bordin AI, Cohen ND, Welsh TH.Transfusion of Rhodococcus equi hyperimmune plasma (REHIP) to neonatal foals is done to reduce the incidence of rhodococcal pneumonia. Objective: To determine effects in newborn foals of REHIP transfusion on serum cortisol concentrations; the association of serum cortisol concentrations with serum globulin concentration and anti-rhodococcal immunoglobulin activity; and cumulative incidence of rhodococcal pneumonia. Methods: Serum samples were collected from 356 newborn foals from 13 New York farms immediately before and after transfusion of 1 L or 2 L of REHIP. Serum samples were assayed for c...
Underberg BA, Van der Vekens E, Drews B, Kaessmeyer S.Equine laminitis is a complex and potentially fatal disease characterized by severe vascular and inflammatory alterations within the equine foot. This study aimed to develop immunohistochemistry (IHC) protocols for the detection of cyclooxygenase-2 (COX-2) and von Willebrand factor (vWF) in equine feet with and without laminitis, post-mortem perfused with paraffin oil. Unassigned: A total of 12 equine forelimbs from 8 horses were utilized in this study, divided into two study cohorts: one with laminitis and the other as a non-laminitis control. To develop the IHC protocols thoroughly, the tiss...
Meeremans M, Devriendt B, Bairiot S, Van Poucke M, Peelman L, Demeyere K, Meyer E, Van Vlierberghe S, De Schauwer C.Macrophages play key roles in tissue homeostasis and regeneration-associated inflammation. Unlike humans, a reliable protocol to obtain and polarise equine monocyte-derived macrophages is lacking. In this study the polarisation of equine macrophages, derived from CD172a peripheral blood monocytes is described. After differentiation, IFN-γ/LPS or IL-4 were used to induce pro- and anti-inflammatory phenotypes, respectively. Evaluation criteria included morphology, mRNA (RT-qPCR) and protein expression (flow cytometry, immunofluorescence), nitric oxide and arginase production, cytokine secretion...
Rask E, Righetti F, Ruiz A, Bjerketorp J, Frosth S, Frykberg L, Jacobsson K, Guss B, Flock JI, Henriques-Normark B, Hartman E, Gustafsson A....Infection of susceptible horses with subspecies (), the causative agent of strangles, is associated with commingling. Exposure may occur among horses at equestrian events, sales, or horses moved among different equine stabling environments. Strangles can affect all horses on a farm, leading to the death of up to 10% of cases depending on their immunity status at the time of infection, the development of complications, the success of biosecurity measures, and the use of vaccination. The current retrospective study used ELISAs to measure the exposure of horses to at a farm that experienced an...
Prasad S, Patel B, Kumar P, Lall R.Postbiotics, which are preparations of inanimate microorganisms and their components, have emerged as a promising functional ingredient in animal health and nutrition. Postbiotics are primarily composed of microbial cell fractions, metabolites, enzymes, vitamins, polysaccharides, and short-chain fatty acids. Unlike probiotics, postbiotics do not contain live microorganisms, which strengthens their greater stability and safety in feed/food formulations. Postbiotics offer several beneficial effects, including antioxidant, anti-inflammatory, immune-modulatory, and antimicrobial actions. They enha...
Ma X, Zhang M, Zhang X, Qi T, Zhang W, Zhao Y, Na L, Zhang Y, Wang XF, Wang X.African horse sickness (AHS) is a lethal vector-borne disease caused by African horse sickness virus (AHSV) and represents a major threat to equine health and the horse industry. In 2020, outbreaks of AHS caused by AHSV serotype 1 (AHSV-1) were reported in Thailand, increasing the risk of AHS introduction into China. Given the safety issues associated with currently available live attenuated AHS vaccines, the development of safer and more effective vaccination strategies is urgently needed. In this study, we constructed a recombinant fowlpox virus (rFPV) expressing the AHSV-1 VP2 protein as a ...
El-Geneady MA, Ramadan RM, Mahdy OA, Kamel MS, Salem MA.Hippobosca equina, a common ectoparasite of horses, poses a significant challenge to equine health worldwide. This study provides a molecular characterization of H. equina and examines its impact on host immune responses and oxidative stress. Genetic analysis of samples from various regions revealed notable homogeneity, indicating limited genetic variation among populations. Phylogenetic analysis demonstrated close genetic relationships among sequences from Egypt, France, Kazakhstan and Portugal, while also showing comparable but more distant identities to sequences from China, Denmark, Finlan...
Yerlikaya Z, Miranda-CasoLuengo R, Jahns H, Byrne O, Meijer WG, Mulcahy G, Walshe N.Cyathostomins are the most prevalent and currently considered the most pathogenic gastrointestinal nematodes in horses. Their life cycle includes an encystment phase within the large intestinal mucosa, where up to 90 % of the total worm burden resides. Clinical disease ranges from chronic protein-losing enteropathy to acute, sometimes fatal, typhlocolitis. Despite their significance, the ecological interplay between cyathostomins, the host immune response, and the gut microbiota remains poorly understood. To our knowledge, this is the first study to investigate these interactions at the mucos...
Liang S, Xu Z, Liu X, Yang Y, Zhao L, Hu C, Hou J, Wei Z, Zhang Y, Li D, Yang J, Zhang J, Bi J, Wang Y, Lou Z.Western equine encephalitis virus (WEEV), a group of encephalitic alphaviruses that cause severe diseases in humans and equids, historically used the very-low-density lipoprotein receptor (VLDLR) as a receptor during infection. However, current epidemic strains no longer use VLDLR as a receptor. In this study, we identify that LA1, LA2, LA3, and LA5 of VLDLR can directly interact with WEEV. Using cryo-electron microscopy, we investigate the structures of complexes formed between WEEV and VLDLR-LBD or other VLDLR fragments. Our findings show that LA1 and LA2 insert into a cleft formed by two ad...
Graide H, Duysens J, Frank T, Mouithys-Mickalad A, Niesten A, Sandersen C, Ceusters J, Serteyn D.Musculoskeletal pathologies present challenges in athletic horses, often leading to functional impairment. The slow or limited regenerative capacity of bone, joint, and tendon/ligament injuries, coupled with the limitations of conventional treatments, highlights the need for innovative therapies such as ortho-biologics and mesenchymal stem/stroma cells. Traditional 2D cell culture systems with fetal bovine serum (FBS) fail to replicate the complexity of the in vivo environment, whereas 3D cultures more accurately mimic native tissue architecture and cell-cell interactions. This study describes...
Cooper BL, Hobbs KJ, Bayless R, Stinson-Miller A, Gruber E, Hepworth-Warren K, Lavoie JP, Sheats MK.Severe equine asthma (sEA) is characterized by increased lower airway neutrophils that contribute to dysregulated inflammation through the release of cytokines, reactive oxygen species and neutrophil extracellular traps (NETs). NETs are composed of cell-free DNA (cfDNA) intercalated with enzymatic proteins and are known to be increased in the lower airway of asthmatic horses. The objectives of this study were two-fold: 1. Determine if cfDNA can be accurately measured in equine bronchoalveolar lavage fluid (BALF) and tracheal wash (TW) with a Qubit 4 fluorometer. 2. Determine whether Qubit-meas...
Mules (Equus mulus), as sterile hybrids between mares and donkeys, present a unique uterine morphology and physiology that remains poorly characterized. This study provides the first histomorphometric evaluation and transcriptional profiling of the endometrium in adult mules. To achieve this, endometrial biopsies were analysed using quantitative stereology, histological classification (Kenney-Doig system), and qPCR of key immune-related and fibrotic genes. Histometric analyses revealed that the stratum spongiosum was the predominant component of the mule endometrium (mean volume density: 84.7...
Zamith Cunha R, Gobbo F, Morini M, Salamanca G, Zanoni A, Bernardini C, Gramenzi A, Chiocchetti R.Evidence suggests that the endocannabinoid system (ECS) is crucial for regulating inflammation, cell proliferation and pain. The ECS is composed of cannabinoid receptors such as type 1 (CBR1), type 2 (CBR2) and GPR55, endocannabinoids and enzymes. Proteins of ECS have previously been localized in the epidermal cells of the horse hooves. Given the physio-pathological role and cellular distribution of the ECS across species, the authors hypothesized that cannabinoid receptors are expressed within the inflammatory cells, fibroblasts and endothelial cells of the equine hoof laminae, going beyond t...
Lobigs M, Pavy M, Hall RA, Lobigs P, Cooper P, Komiya T, Toriniwa H, Petrovsky N.Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a ...
Posthuma CC, Pedersen KW, Lu Z, Joosten RG, Roos N, Zevenhoven-Dobbe JC, Snijder EJ.The replication/transcription complex of the arterivirus equine arteritis virus (EAV) is associated with paired membranes and/or double-membrane vesicles (DMVs) that are thought to originate from the endoplasmic reticulum. Previously, coexpression of two putative transmembrane nonstructural proteins (nsp2 and nsp3) was found to suffice to induce these remarkable membrane structures, which are typical of arterivirus infection. Here, site-directed mutagenesis was used to investigate the role of nsp3 in more detail. Liberation of the hydrophobic N terminus of nsp3, which is normally achieved by c...
Cross AR, Higson FK, Jones OT, Harper AM, Segal AW.1. The absorption coefficient of human neutrophil plasma-membrane reduced-minus-oxidized cytochrome b-245 was determined [delta epsilon (mM; 559-540 nm) = 21.6 cm-1]. 2. Neutrophil polymorphonuclear leucocytes (neutrophils) were prepared from human, ox, horse and pig blood. In each case plasma-membrane fractions were found to contain low-potential cytochrome b. When membranes from horse neutrophils were incubated anaerobically with either NADH or NADPH the cytochrome b became reduced. Prior stimulation of the cells with phorbol myristate acetate did not increase the rate or extent of cytochrom...
Barberini DJ, Freitas NP, Magnoni MS, Maia L, Listoni AJ, Heckler MC, Sudano MJ, Golim MA, da Cruz Landim-Alvarenga F, Amorim RM.Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identical in vitro conditions, to compare these sources for research or an allogeneic therapy cell bank. Methods: The BM-MS...
Lewis NS, Daly JM, Russell CA, Horton DL, Skepner E, Bryant NA, Burke DF, Rash AS, Wood JL, Chambers TM, Fouchier RA, Mumford JA, Elton DM, Smith DJ.Equine influenza virus is a major respiratory pathogen in horses, and outbreaks of disease often lead to substantial disruption to and economic losses for equestrian industries. The hemagglutinin (HA) protein is of key importance in the control of equine influenza because HA is the primary target of the protective immune response and the main component of currently licensed influenza vaccines. However, the influenza virus HA protein changes over time, a process called antigenic drift, and vaccine strains must be updated to remain effective. Antigenic drift is assessed primarily by the hemagglu...
Salinovich O, Payne SL, Montelaro RC, Hussain KA, Issel CJ, Schnorr KL.Previous results from our laboratory have demonstrated that equine infectious anemia virus displays structural variations in its surface glycoproteins and RNA genome during passage and chronic infections in experimentally infected Shetland ponies (Montelaro et al., J. Biol. Chem. 259:10539-10544, 1984; Payne et al., J. Gen. Virol. 65:1395-1399, 1984). The present study was undertaken to obtain an antigenic and biochemical characterization of equine infectious anemia virus isolates recovered from an experimentally infected pony during sequential disease episodes, each separated by intervals of ...
Guest DJ, Smith MR, Allen WR.Autologous mesenchymal progenitor cells (MPCs) purified from bone marrow aspirates are being used in the treatment of superficial digital flexor tendon (SDFT) injuries in the horse with promising results. In this study the fate of autologous and allogeneic MPCs following injection into the SDFT was monitored by stable transfection of MPCs with green fluorescent protein (GFP). Small lesions were created manually in one forelimb SDFT of 2 horses and injected with autologous MPCs, allogeneic MPCs or bone marrow supernatant alone. Post mortem examinations performed after 10 or 34 days revealed GFP...
Pauvolid-Corrêa A, Campos Z, Juliano R, Velez J, Nogueira RM, Komar N.A recent study reported neutralizing antibodies to West Nile virus (WNV) in horses from four ranches of southern Pantanal. To extend that study, a serosurvey for WNV and 11 Brazilian flaviviruses was conducted with 760 equines, 238 sheep and 61 caimans from 17 local cattle ranches. Among the tested equines, 32 were collected from a ranch where a neurologic disorder outbreak had been recently reported. The sera were initially screened by using a blocking ELISA and then titrated by 90% plaque-reduction neutralization test (PRNT90) for 12 flaviviruses. Employing the criterion of 4-fold greater ti...
Möstl E, Messmann S, Bagu E, Robia C, Palme R.After 14C-labelled cortisol infusion in ponies and pigs, faecal samples were collected. Extraction of 0.5 g faeces with 5 ml 80-90% methanol yielded the highest radioactivity in the supernatant. Most of the metabolites were ether soluble. After high performance liquid chromatography (HPLC), the presence of immunoreactive metabolites was demonstrated by measuring each HPLC fraction using enzyme immunoassays for cortisol, corticosterone and 11-oxoaetiocholanolone. Only the assay for 11-oxoaetiocholanolone revealed peaks with co-eluting radioactivity. For biological validation of the test system,...
Bowen RA, Nemeth NM.West Nile virus emerged recently in North America as a serious human and animal pathogen. This review summarizes the use of experimental infections with West Nile virus in diverse vertebrate species that have been used to answer fundamental questions about the host response, pathogenesis of West Nile virus infection and virus evolution. Results: West Nile virus has an extremely broad vertebrate host range. Infection of common species of birds has defined those with high vs. low potential to serve as amplifying hosts for the virus. In general, mammals (primates, horses, companion animals) are d...
Lindenberg F, Krych L, Fielden J, Kot W, Frøkiær H, van Galen G, Nielsen DS, Hansen AK.Billions of bacteria inhabit the gastrointestinal tract. Immune-microbial cross talk is responsible for immunological homeostasis, and symbiotic microbial species induce regulatory immunity, which helps to control the inflammation levels. In this study we aimed to identify species within the equine intestinal microbiota with the potential to induce regulatory immunity. These could be future targets for preventing or treating low-grade chronic inflammation occurring as a result of intestinal microbial changes and disruption of the homeostasis. 16S rRNA gene amplicon sequencing was performed on ...
Wagner B, Freer H.The detection and quantification of equine cytokines has been hampered by the lack of antibodies for many years. With the development of antibody pairs for equine cytokines during the past years, the quantification of these essential regulators of the immune response became possible. After being successfully tested by enzyme-linked immunosorbent assays (ELISA), three of these anti-cytokine reagents were used here to establish the first cytokine multiplex assay for equine IL-4, IL-10 and IFN-alpha. A fluorescent bead-based system was used as matrix for this assay that allows the simultaneous de...
Carrade Holt DD, Wood JA, Granick JL, Walker NJ, Clark KC, Borjesson DL.Mesenchymal stem cells (MSCs) are used in both human clinical trials and veterinary medicine for the treatment of inflammatory and immune-mediated diseases. MSCs modulate inflammation by decreasing the cells and products of the inflammatory response. Stimulated equine MSCs from bone marrow (BM), adipose tissue (AT), cord blood (CB), and umbilical cord tissue (CT) inhibit lymphocyte proliferation and decrease inflammatory cytokine production. We hypothesized that equine MSCs inhibit T cell proliferation through secreted mediators and that MSCs from different tissue sources decrease T cell proli...
Mehdizadeh Gohari I, Parreira VR, Nowell VJ, Nicholson VM, Oliphant K, Prescott JF.A role for type A Clostridium perfringens in acute hemorrhagic and necrotizing gastroenteritis in dogs and in necrotizing enterocolitis of neonatal foals has long been suspected but incompletely characterized. The supernatants of an isolate made from a dog and from a foal that died from these diseases were both found to be highly cytotoxic for an equine ovarian (EO) cell line. Partial genome sequencing of the canine isolate revealed three novel putative toxin genes encoding proteins related to the pore-forming Leukocidin/Hemolysin Superfamily; these were designated netE, netF, and netG. netE a...
Pirie RS.Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fu...
Cheevers WP, McGuire TC.Equine infectious anemia (EIA) is a chronic, relapsing infectious disease of horses caused by a nononcogenic retrovirus. Virus persists in infected animals for life and can be reliably detected by serologic tests that measure levels of antibody to the major structural protein of the virus. Periodic virus replication in macrophages leads to an immunologically mediated acute disease characterized primarily by severe anemia. Recrudescence of acute EIA is the result of antigenic variation of the surface glycoprotein of EIA virus. The frequency and severity of clinical episodes of EIA decrease in m...
Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS.The term "equine asthma" has been proposed as a unifying descriptor of inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and summer pasture-associated obstructive airway disease. Whilst the term will increase comprehensibility for both the lay and scientific communities, its biologic relevance must be compared and contrasted to asthma in human medicine, recognizing the limited availability of peer-reviewed equine-derived data, which are largely restricted to clinical signs, measures of airway obstruction and inflammation and response to therapy. Such limitations constrain ...
von Bargen K, Haas A.The soil actinomycete Rhodococcus equi is a pulmonary pathogen of young horses and AIDS patients. As a facultative intracellular bacterium, R. equi survives and multiplies in macrophages and establishes its specific niche inside the host cell. Recent research into chromosomal virulence factors and into the role of virulence plasmids in infection and host tropism has presented novel aspects of R. equi infection biology and pathogenicity. This review will focus on new findings in R. equi biology, the trafficking of R. equi-containing vacuoles inside host cells, factors involved in virulence and ...
Radcliffe CH, Flaminio MJ, Fortier LA.Mesenchymal progenitor cells (MPCs) are often characterized using surface markers after expansion and treatment in culture. There are no studies directly comparing gene and protein markers in undifferentiated samples during the very early phases of culture. The goal of this study was to evaluate temporal gene and protein expression changes during establishment of equine MPC cultures. Bone marrow aspirate was obtained from 35 horses and processed by density gradient centrifugation. In freshly isolated bone marrow, mononuclear cells had variable expression of CD44, CD11a/CD18, CD90, and CD45RB c...
Brault AC, Powers AM, Chavez CL, Lopez RN, Cachón MF, Gutierrez LF, Kang W, Tesh RB, Shope RE, Weaver SC.Eastern equine encephalitis virus (EEEV), the sole species in the EEE antigenic complex, is divided into North and South American antigenic varieties based on hemagglutination inhibition tests. Here we describe serologic and phylogenetic analyses of representatives of these varieties, spanning the entire temporal and geographic range available. Nucleotide sequencing and phylogenetic analyses revealed additional genetic diversity within the South American variety; 3 major South/Central American lineages were identified including one represented by a single isolate from eastern Brazil, and 2 lin...
Cassano JM, Schnabel LV, Goodale MB, Fortier LA.Inflammatory licensed mesenchymal stem cells (MSCs) have the ability to promote functional tissue repair. This study specifically sought to understand how the recipient tissue environment reciprocally affects MSC function. Inflammatory polarized macrophages, modeling an injured tissue environment, were exposed to licensed MSCs, and the resultant effects of MSC immunomodulation and functionality of the MSC secretome on chondrocyte homeostasis were studied. Inflammatory licensed MSCs were generated through priming with either IFN-γ or polyinosinic:polycytidylic acid (poly I:C). Macrophages were...
Carrade DD, Affolter VK, Outerbridge CA, Watson JL, Galuppo LD, Buerchler S, Kumar V, Walker NJ, Borjesson DL.BACKGROUND AIMS. The use of allogeneic mesenchymal stem cells (MSC) to treat acute equine lesions would greatly expand equine cellular therapy options; however, the safety and antigenicity of these cells have not been well-studied. We hypothesized that equine allogeneic umbilical cord tissue (UCT)-derived MSC would not elicit acute graft rejection or a delayed-type hypersensitivity response when injected intradermally. METHODS. Six Quarterhorse yearlings received 12 intradermal injections (autologous MSC, allogeneic MSC, positive control and negative control, in triplicate) followed by the sam...
Munderloh UG, Madigan JE, Dumler JS, Goodman JL, Hayes SF, Barlough JE, Nelson CM, Kurtti TJ.The equine granulocytic ehrlichiosis agent, Ehrlichia equi, is closely related or identical to the human granulocytic ehrlichiosis (HGE) agent. Both are suspected of being transmitted by ticks. We have successfully isolated E. equi in a cell line, IDE8, derived from a putative vector, the tick Ixodes scapularis. Peripheral blood leukocytes from an experimentally infected horse were inoculated onto IDE8 monolayers. Cultures were incubated in a candle jar at 34 degrees C in tick cell culture medium with NaHCO3 and an organic buffer [3-(N-morpholino)-propanesulfonic acid] (MOPS). Within 2 weeks, ...
Takai S, Koike K, Ohbushi S, Izumi C, Tsubaki S.Antigens of Rhodococcus equi were analyzed by immunoblotting with naturally infected foal sera. Immunoblots of whole-cell antigen preparations of clinical isolates of R. equi revealed that major protein bands with molecular masses of 15 to 17 kDa were present in all clinical isolates tested and all isolates virulent for mice. In contrast, the 15- to 17-kDa antigens were not identified by immunoblotting in ATCC 6939, a type strain of R. equi that was avirulent for mice. Whole-cell antigens of 102 environmental isolates were investigated by immunoblotting and the mouse pathogenicity test. Twenty...
Nara PL, Garrity RR, Goudsmit J.The production of immunoglobulin capable of neutralizing the infectivity of a virus represents one of the most remarkable molecular accomplishments of the host's available immune defenses. It should be no surprise that a virus that has existed in the parenchyma of the immune system has evolved as an equally dynamic molecule (i.e., viral envelope) for survival. Neutralizing immunoglobulin (Ig) can best serve the host under conditions where the invading pathogen requires a well-defined cell-free state for establishing an infection or transmission. Evidence for a controlling and therefore protect...
Browning GF, Fitzgerald TA, Chalmers RM, Snodgrass DR.Equine rotavirus FI23 was shown to be prototypic of a novel G serotype, provisionally G14, by cross-neutralization and VP7 sequence determination. Although distinct, there are as few as six differing amino acid residues (92, 94, 96, 146, 147, and 221) in the VP7 antigenic regions of FI23 and G3 rotaviruses.
Shehu-Xhilaga M, Ablan S, Demirov DG, Chen C, Montelaro RC, Freed EO.The Gag proteins of a number of different retroviruses contain late or L domains that promote the release of virions from the plasma membrane. Three types of L domains have been identified to date: Pro-Thr-Ala-Pro (PTAP), Pro-Pro-X-Tyr, and Tyr-Pro-Asp-Leu. It has previously been demonstrated that overexpression of the N-terminal, E2-like domain of the endosomal sorting factor TSG101 (TSG-5') inhibits human immunodeficiency virus type 1 (HIV-1) release but does not affect the release of the PPPY-containing retrovirus murine leukemia virus (MLV), whereas overexpression of the C-terminal portion...
Blitvich BJ, Bowen RA, Marlenee NL, Hall RA, Bunning ML, Beaty BJ.We evaluated the ability of epitope-blocking enzyme-linked immunosorbent assays (ELISAs) to detect West Nile virus (WNV) antibodies in domestic mammals. Sera were collected from experimentally infected horses, cats, and pigs at regular intervals and screened in ELISAs and plaque reduction neutralization tests. The diagnostic efficacies of these techniques were similar.
Vannella KM, Moore BB.Idiopathic pulmonary fibrosis (IPF) remains exactly that. The disease originates from an unknown cause, and little is known about the mechanisms of pathogenesis. While the disease is likely multi-factorial, evidence is accumulating to implicate viruses as co-factors (either as initiating or exacerbating agents) of fibrotic lung disease. This review summarizes the available clinical and experimental observations that form the basis for the hypothesis that viral infections may augment fibrotic responses. We review the data suggesting a link between hepatitis C virus, adenovirus, human cytomegalo...
