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Topic:Interferons
Interferons are a group of signaling proteins produced by the cells of the immune system in horses in response to viral infections and other immune challenges. They are part of the innate immune response and help regulate the activity of the immune system by inhibiting viral replication and modulating the immune response. In horses, interferons are categorized into types I, II, and III, with type I interferons, such as interferon-alpha and interferon-beta, being the most extensively studied. These proteins are integral to the horse's defense mechanisms against viral pathogens and are also explored for their therapeutic potential. This page compiles peer-reviewed research studies and scholarly articles that investigate the production, function, and clinical applications of interferons in equine health.
Genomic analysis and mRNA expression of equine type I interferon genes. This study aimed at identifying all of the type I interferon (IFN) genes of the horse and at monitoring their expression in equine cells on in vitro induction. We identified 32 putative type I IFN loci on horse chromosome 23 and an unplaced genomic scaffold. A phylogentic analysis characterized these into 8 different type I IFN classes, that is, putative functional genes for 6 IFN-α, 4 IFN-β, 8 IFN-ω (plus 4 pseudogenes), 3 IFN-δ (plus 1 pseudogene), 1 IFN-κ and 1 IFN-ε, plus 1 IFN-ν pseudogene, and 3 loci belonging to what has previously been called IFN-αω. Our analyses indicate that...
Cytokines and angiogenesis in the corpus luteum. In adults, physiological angiogenesis is a rare event, with few exceptions as the vasculogenesis needed for tissue growth and function in female reproductive organs. Particularly in the corpus luteum (CL), regulation of angiogenic process seems to be tightly controlled by opposite actions resultant from the balance between pro- and antiangiogenic factors. It is the extremely rapid sequence of events that determines the dramatic changes on vascular and nonvascular structures, qualifying the CL as a great model for angiogenesis studies. Using the mare CL as a model, reports on locally produced c...
Establishment and evaluation of a bead-based luminex assay allowing simultaneous quantification of equine IL-12 and IFN-γ. Interleukin-12 (IL-12) and interferon gamma (IFN-γ) are key cytokines in immunemediated equine melanoma therapy. Currently, a method for accurate simultaneous quantification of these equine cytokines is lacking. Therefore, we sought to establish an assay that allows for accurate and simultaneous quantification of equine IL-12 (eIL-12) and IFN-γ (eIFN-γ). Methods: Several antibodies were evaluated for cross-reactivity to eIL-12 and eIFN-γ and were used to establish a bead-based Luminex assay, which was subsequently applied to quantify cytokine concentrations in biological samples. Results: ...
Differentiation and activation of equine monocyte-derived dendritic cells are not correlated with CD206 or CD83 expression. Dendritic cells (DC) are the main immune mediators inducing primary immune responses. DC generated from monocytes (MoDC) are a model system to study the biology of DC in vitro, as they represent inflammatory DC in vivo. Previous studies on the generation of MoDC in horses indicated that there was no distinct difference between immature and mature DC and that the expression profile was distinctly different from humans, where CD206 is expressed on immature MoDC whereas CD83 is expressed on mature MoDC. Here we describe the kinetics of equine MoDC differentiation and activation, analysing both ph...
[Experimental and clinicolaboratory evaluation of complex therapy efficacy in arboviral infections]. Search for drugs efficient in prophylaxis and treatment of dangerous infections (especially arboviral ones) is rather actual, since no specific therapy is available. Many-year investigations of interferon inductors showed that they had immunomodulating, antiviral and antiinflammatory effects and were low toxic. The present study demonstrated that the protective effect was the following: Venezuelan equine encephalitis (VEE)--cycloferon > amixin = ridostin, Rift Valley fever (RVF)--cycloferon > amixin > ridostin, predator pox (PP)--cycloferon > amixin = ridostin, that was obvious tha...
Immunogenomic analysis of insect bite hypersensitivity in a model horse population. Equine insect bite hypersensitivity (IBH) is a seasonal IgE-mediated dermatosis caused by bites of insects of the genus Culicoides. A familial predisposition for the disease has been shown but, except for the MHC, the genes involved have not been identified so far. An immunogenomic analysis of IBH was performed in a model population of Old Kladruby horses, all living in the same environment. Clinical signs of IBH were used as phenotypic manifestation of IBH. Furthermore, total serum IgE levels were determined in the sera of these horses and used as an independent phenotypic marker for the immu...
Hydrocortisone inhibits IFN-γ production in equine, ovine, and bovine PBMCs. Hydrocortisone is widely accepted as an anti-inflammatory agent and there are many products available containing hydrocortisone as an active ingredient. Surprisingly, there is little data available specifically on the immunological effects of hydrocortisone in large animals. Glucocorticoids are well-characterized for their ability to repress inflammation via a wide variety of mechanisms including suppression of cytokine production. In this study the effects of hydrocortisone on IFN-γ production by equine, bovine, and ovine PBMCs were assessed using flow cytometric or ELISpot analysis. Hydroco...
Age-related changes in intracellular expression of IFN-γ and TNF-α in equine lymphocytes measured in bronchoalveolar lavage and peripheral blood. 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...
Effect of cytokines and ovarian steroids on equine endometrial function: an in vitro study. Regulation of immune-endocrine interactions in the equine endometrium is not fully understood. The aims of the present study were to: (1) investigate the presence of tumour necrosis factor alpha (TNF), interferon gamma (IFNG), Fas ligand (FASLG) and their receptors in the mare endometrium throughout the oestrous cycle; and (2) assess endometrial secretory function (prostaglandins), angiogenic activity and cell viability in response to TNF, oestradiol (E2), progesterone (P4) and oxytocin (OXT). Transcription of TNF and FASLG mRNA increased during the early and late luteal phase (LP), whereas IF...
The promoter region of interferon-gamma is hypermethylated in neonatal foals and its demethylation is associated with increased gene expression. While born with a limited production, foals' interferon-gamma (IFN-γ) expression increases after birth. The underlying mechanisms remain unknown. DNA methylation is considered to be involved. Therefore, the DNA methylation status of the Ifng promoter in CD4(+) cells from neonatal foal was determined using a methylation-specific PCR (MSP), and its relevance to IFN-γ mRNA expression was estimated. The effect of environment on the DNA methylation was also evaluated by comparing ponies that were kept in a barn versus those on pasture. The DNA in the Ifng promoter was hypermethylated and its deme...
Transcriptome analyses of bovine, porcine and equine endometrium during the pre-implantation phase. Different reproductive strategies evolved in various mammalian groups to achieve recognition, establishment and maintenance of pregnancy. The complexity of these processes is reflected by a high incidence of embryonic loss during this critical period in many mammalian species. Besides studies in mice and humans a number of transcriptome studies of endometrial tissue samples and also of early embryos have been performed during the pre-implantation phase in cattle, swine and horse to identify genes associated with embryo-maternal interaction. Results of these studies are reviewed and compared be...
Effects of a single dose of enrofloxacin on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. To evaluate effects of a single dose of enrofloxacin (5 mg/kg, IV) on body temperature and tracheobronchial neutrophil count in healthy Thoroughbreds premedicated with interferon-α and undergoing long-distance transportation. Methods: 32 healthy Thoroughbreds. Methods: All horses received interferon-α (0.5 U/kg, sublingually, q 24 h) as an immunologic stimulant for 2 days before transportation and on the day of transportation. Horses were randomly assigned to receive enrofloxacin (5 mg/kg, IV, once; enrofloxacin group) or saline (0.9% NaCl) solution (50 mL, IV, once; control group) ≤ 1 hou...
Modeling within-host dynamics of influenza virus infection including immune responses. Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and ...
The determination of in vivo envelope-specific cell-mediated immune responses in equine infectious anemia virus-infected ponies. Distinct from human lentivirus infection, equine infectious anemia virus (EIAV)-infected horses will eventually enter an inapparent carrier state in which virus replication is apparently controlled by adaptive immune responses. Although recrudescence of disease can occur after immune suppression, the actual immune correlate associated with protection has yet to be determined. Therefore, EIAV provides a model for investigating immune-mediated protective mechanisms against lentivirus infection. Here, we have developed a method to monitor EIAV-envelope specific cellular immunity in vivo. An EIA c...
Effect of strenuous exercise and ex vivo TLR3 and TLR4 stimulation on inflammatory gene expression in equine pulmonary leukocytes. The effects of strenuous exercise and ex vivo stimulation of TLR3 and TLR4 pathways on the expression of six inflammatory genes in equine pulmonary leukocytes were investigated. The genes tested were interferon-beta (IFN-β), interleukin-1-beta (IL-1β), interleukin-6 (IL-6), interferon gamma-induced protein 10 (IP-10), chemokine (c-c motif) ligand 5 (RANTES) and tumor necrosis factor-alpha (TNF-α). We hypothesized that strenuous exercise would modulate basal gene expression on one hand and modulate the response to bacterial lipopolysaccharide (LPS) and to polyinosinic:polycytidylic acid (Pol...
Cytokine production and proliferation upon in vitro oligodeoxyribonucleotide stimulation of equine peripheral blood mononuclear cells. Synthetic oligodeoxyribonucleotides (ODN) may prove useful immune modulators in equine medicine. It is however important to assess the effects of each specific ODN in the species it is intended to be used in. The present study therefore aimed to evaluate some ODN for induction of cytokine production; i.e. type I interferons (IFN), IFN-γ, tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and proliferation of equine peripheral blood mononuclear cells (PBMC). A panel of four ODN containing unmethylated cytosine-guanosine sequences (CpG) was used: ODN 1 and ODN 8 repre...
Cytokines tumor necrosis factor-α and interferon-γ participate in modulation of the equine corpus luteum as autocrine and paracrine factors. Knowledge on the regulation of corpus luteum (CL) function in the mare is scarce. In this study, the presence of cytokines tumor necrosis factor alpha (TNF) and interferon gamma (IFNG), and their receptors (TNFRI, TNFRII and IFNRI), was investigated in equine CL throughout the luteal phase. The effects of TNF and IFNG on secretory function and viability of luteal cells were defined in vitro. Cytokine ligands and receptors were present in steroidogenic and endothelial cells. Protein expression for TNF was greater in mid-phase and regressing CL, while TNFRI was increased in regressing CL and TNF...
Effect of progesterone on the in vitro response of peripheral blood mononuclear cells stimulated by Escherichia coli in mares. Escherichia coli(E. coli) isolated from the uterus of a Thoroughbred mare with bacterial endometritis was used to evaluate the effect of progesterone (P(4)) on the immune response of mares. Peripheral blood mononuclear cells (PBMCs) were collected from 10 nonpregnant clinically healthy adult mares (range, 4-12 years) during diestrus, four Thoroughbreds and six Hokkaido native horses. Cell proliferation and expression of cytokine mRNA, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-10, of PBMCs stimulated with E. coli and P(4) were examined in vitro. P(4) was...
ISCOM-matrix-based equine influenza (EIV) vaccine stimulates cell-mediated immunity in the horse. The humoral immune response induced by ISCOM-matrix (Immuno Stimulating COMplex-Matrix)-adjuvanted equine influenza virus (EIV) vaccine is well documented in horses. ISCOM-matrix adjuvanted vaccines against human influenza are strong inducers of cell-mediated immunity (CMI), including T cell proliferation and virus-specific cytotoxic T cell. In the horse, the CMI response to equine influenza vaccination is less well characterised. An ISCOM-based vaccine has been shown to induce interferon gamma (IFN-γ) synthesis, a CMI marker, in the horse, but this has not been shown for the ISCOM-matrix vac...
The role of proliferation in the regulation of interferon gamma (IFNγ) expression in foals. Interferon-gamma (IFNγ) plays an important role against viral and intracellular bacterial infections and its production is deficient in foals. Cellular proliferation provides an opportunity for de novo gene expression, though little is known about its role in regulating IFNγ expression in foals. While stimulation of foal peripheral blood mononuclear cells (PBMCs) with concanavalin A (ConA) increased the frequency of IFNγ(+) cells, the overall percentage of IFNγ(+) cells remained below that of adults. By contrast, the proliferative response of foal PBMC was significantly greater than that o...
In vivo induction of interferon gamma expression in grey horses with metastatic melanoma resulting from direct injection of plasmid DNA coding for equine interleukin 12. Whole blood pharmacokinetics of intratumourally injected naked plasmid DNA coding for equine Interleukin 12 (IL-12) was assessed as a means of in vivo gene transfer in the treatment of melanoma in grey horses. The expression of induced interferon gamma (IFN-g) was evaluated in order to determine the pharmacodynamic properties of in vivo gene transduction. Seven grey horses bearing melanoma were injected intratumourally with 250 µg naked plasmid DNA coding for IL-12. Peripheral blood and biopsies from the injection site were taken at 13 time points until day 14 post injection (p.i.). Samples w...
MyD88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection. 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...
Equine ELISPOT assay to study secretion of IFNγ and IL-4 from peripheral blood mononuclear cells. Human and mouse immune system cells are the most frequently used specimens in ELISPOT assays. In an effect to expand the application of ELISPOT assay to other species, we developed matched antibody pairs for ready-to-use kits designed for studying the frequency of equine IFNγ- and IL-4-secreting peripheral blood mononuclear cells (PBMCs). Equine PBMCs were stimulated with either concanavalin A (Con A) or calcium ionomycin mixed with phorbol 12-myristate 13-acetate (CaI + PMA). We found that Con A, in general, had a more profound stimulating effect than CaI + PMA on IL-4 secretion, whereas bot...
The effect of environment on interferon-gamma production in neonatal foals. While interferon-gamma (IFNγ) plays an important role in protection against viral and intracellular bacterial infections, its production in neonates is deficient. Exposure to environmental antigens can promote the maturation of the immune system of neonatal humans and mice. We hypothesize that exposure to high level of microbial components would increase the production of IFNγ in neonatal foals. To test this hypothesis, one group of foals was placed into stalls three times a week for 8 weeks. A second group of foals remained on pasture. Air samples were collected from the barn and pasture fo...
Lawsonia intracellularis-specific interferon γ gene expression by peripheral blood mononuclear cells in vaccinated and naturally infected foals. The cell-mediated immune response to Lawsonia intracellularis, the agent of equine proliferative enteropathy (EPE), was investigated in vaccinated and naturally infected foals. Interferon (IFN)-γ gene expression was determined in peripheral blood mononuclear cells collected from vaccinated (n=6) and control foals (n=6) every 30 days for 180 days following first vaccine administration, and from clinically affected foals (n=16) within 7-10 days of diagnosing EPE. Seroconversion (immunoperoxidase monolayer assay titer ≥60) occurred in 5/6 vaccinated foals between 60 and 90 days following the f...
Characterization of the interferon gamma response to Lawsonia intracellularis using an equine proliferative enteropathy challenge (EPE) model. Lawsonia intracellularis is the etiological agent of infectious intestinal hyperplasia for which several clinical diseases have been described including proliferative enteropathy (PE), intestinal adenomatosis, and ileitis. While initially recognized as the causative agent of PE in pigs, L. intracellularis is now viewed as an emerging cause of intestinal hyperplasia in a wide range of mammalian species, including horses. Equine proliferative enteropathy (EPE) has been reported worldwide though definitive diagnosis is difficult and the epidemiology of the disease remains poorly understood. Weanl...
Exercise-induced increases in inflammatory cytokines in muscle and blood of horses. Studies have demonstrated increases in mRNA expression for inflammatory cytokines following exercise in horses and have suggested those markers of inflammation may play a role in delayed onset muscle soreness. However, measurement of mRNA expression in white blood cells is an indirect method. No studies to date have documented the cytokine response to exercise directly in muscle in horses. Objective: This study tested the hypothesis that exercise increases cytokine markers of inflammation in blood and muscle. Methods: Blood and muscle biopsies were obtained from 4 healthy, unfit Standardbred m...
Effect of Propionibacterium acnes-containing immunostimulant on interferon-gamma (IFNγ) production in the neonatal foal. Production of the Th1 cytokine interferon gamma (IFNγ) is associated with resistance to intracellular pathogens, including Rhodococcus equi. While neonatal foals are initially deficient in IFNγ production, expression of this cytokine increases throughout their first year of life. This is presumably the result of stimulation by environmental antigens including pathogen associated molecular patterns (PAMPS) signaling through toll-like receptors (TLR). This increased expression of IFNγ is likewise associated with an age-related resistance to R. equi infection. While immunostimulants containing...
The expression of interferon-stimulated gene 15 in equine endometrium. Establishment of pregnancy is critically dependent upon a precisely orchestrated embryo-maternal interaction leading to a receptive uterine environment. The up-regulation of the interferon-stimulated protein 15 kDa (ISG15) during pregnancy has been described in various species and has been hypothesized to be part of the molecular repertoire that makes the uterus receptive to conceptus development. In the current study, the expression of ISG15 and enzymes involved in ISG15ylation was examined at the mRNA and protein level in equine endometrium at Day 14 of the luteal phase and at Day 14 and 50 ...
Identification of three novel superantigen-encoding genes in Streptococcus equi subsp. zooepidemicus, szeF, szeN, and szeP. The acquisition of superantigen-encoding genes by Streptococcus pyogenes has been associated with increased morbidity and mortality in humans, and the gain of four superantigens by Streptococcus equi is linked to the evolution of this host-restricted pathogen from an ancestral strain of the opportunistic pathogen Streptococcus equi subsp. zooepidemicus. A recent study determined that the culture supernatants of several S. equi subsp. zooepidemicus strains possessed mitogenic activity but lacked known superantigen-encoding genes. Here, we report the identification and activities of three novel ...
