Interleukin-17A as a Biomarker for Bovine Tuberculosis.
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ABSTRACT:
SUBMITTER: Waters WR
PROVIDER: S-EPMC4744917 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:INTRODUCTION:Morphea is a disease included in the group of scleroderma type autoimmune diseases. Interleukin (IL)-17A may play a role at every stage of its pathogenesis. The study aimed at evaluation of IL-17A and IL-23 (as the main cytokine which is supposed to stimulate and maintain synthesis of IL-17) in pathogenesis of morphea. MATERIAL AND METHODS:The studies were performed on 41 blood samples from patients with morphea. Skin was sampled from 29 patients. The evaluation included: (1) expression of IL-17A and IL-23 genes in peripheral blood mononuclear cells (PBMC) using real-time polymerase chain reaction (PCR), (2) plasma concentrations of IL-17A and IL-23 using ELISA, (3) expression of IL-17A and IL-23 genes in skin using real-time PCR. RESULTS:The results of gene expression are expressed as median number of copies per million copies of GAPDH. Higher expression of IL-17A has been demonstrated in PBMC of morphea vs. control group (2630 and 1906 respectively; p = 0.004), accompanied by absence of significant differences in its plasma concentration (10 pg/ml in both groups) and by lowered expression in affected skin (9119 and 19113 respectively; p = 0.036). The results failed to demonstrate elevated IL-23 plasma concentration in morphea vs. control group (5 pg/ml and 6 pg/ml respectively; p = 0.335) or its increased expression in the skin (292 vs. 427; p = 0.383), although we noted its increased expression in PBMC (4419 vs. 808; p < 0.001). CONCLUSIONS:BASED ON THE OBSERVED CORRELATIONS WE SUGGEST THAT: (1) IL-17A does not represent a factor which promotes tissue injury in morphea, (2) IL-23 may playa role in pathogenesis of morphea.
| S-EPMC3542501 | biostudies-literature
Project description:Bovine tuberculosis (bTB) is primarily caused by infection with Mycobacterium bovis, which belongs to the Mycobacterium tuberculosis complex. The airborne route is considered the most common for transmission of M. bovis, and more than 15% of cattle with bTB shed the Mycobacterium, which can be detect by nested PCR to amplify mycobacterial mpb70 from a nasal swab from a cow. To screen for cytokines fostering early and accurate detection of bTB, peripheral blood mononuclear cells were isolated from naturally M. bovis-infected, experimentally M. bovis 68002-infected, and uninfected cattle, then these cells were stimulated by PPD-B, CFP-10-ESAT-6 (CE), or phosphate-buffered saline (PBS) for 6 h. The levels of interferon gamma (IFN-γ), IFN-γ-induced protein 10 (IP-10), IL-6, IL-12, IL-17A, and tumor necrosis factor alpha mRNA were measured using real-time PCR. To explore the cytokines associated with different periods of M. bovis infection, cattle were divided into three groups: PCR-positive, PCR-negative, and uninfected using the tuberculin skin test, CFP-10/ESAT-6/TB10.4 protein cocktail-based skin test, IFN-γ release assay (IGRA), CFP-10/ESAT-6 (CE)-based IGRA, and nested PCR. The expression of IP-10, IL-17A, and IFN-γ proteins induced by PPD-B, CE, or PBS was detected by ELISA. The results showed that levels of PPD-B-stimulated IL-17A and IP-10 (mRNA and protein), and CE-induced IP-10 (mRNA and protein) were significantly higher in cattle naturally or experimentally infected with M. bovis than in those that were uninfected. The levels of PPD-B- or CE-induced IL-17A and IP-10 (protein) could be used to differentiate M. bovis-infected calves from uninfected ones for 6 to 30 weeks post-infection, whereas PPD-B- and CE-induced IP-10 and IL-17A mRNA expression could be used to differentiate M. bovis-infected calves from uninfected ones between 6 and 58 weeks post-infection. However, CE-induced IL-17A (protein) was not a reliable indicator of M. bovis infection in cattle that were confirmed positive for infection by nested PCR. Furthermore, the levels of PPD-B- or CE-induced IP-10 and IL-17A protein were lower than IFN-γ in M. bovis-infected cattle. Therefore, IL-17A and IP-10 protein are not suitable biomarkers for bTB. Antigen-induced IP-10 mRNA should be analyzed further for their potential to be used in the diagnosis of bTB.
| S-EPMC5845669 | biostudies-literature
Project description:The excellent clinical efficacy of anti-interleukin 17A (IL-17A) biologics on psoriasis indicates a crucial pathogenic role of IL-17A in this autoinflammatory skin disease. IL-17A accelerates the proliferation of epidermal keratinocytes. Keratinocytes produce a myriad of antimicrobial peptides and chemokines, such as CXCL1, CXCL2, CXCL8, and CCL20. Antimicrobial peptides enhance skin inflammation. IL-17A is capable of upregulating the production of these chemokines and antimicrobial peptides in keratinocytes. CXCL1, CXCL2, and CXCL8 recruit neutrophils and CCL20 chemoattracts IL-17A-producing CCR6+ immune cells, which further contributes to forming an IL-17A-rich milieu. This feed-forward pathogenic process results in characteristic histopathological features, such as epidermal hyperproliferation, intraepidermal neutrophilic microabscess, and dermal CCR6+ cell infiltration. In this review, we focus on IL-17A and keratinocyte interaction regarding psoriasis pathogenesis.
| S-EPMC7072868 | biostudies-literature
Project description:BACKGROUND: Early and unambiguous detection of bovine tuberculosis (bTB), a significant disease of cattle worldwide, is necessary to control the spread of infection to other animals and humans. Current testing strategies are laborious, time consuming and heavily reliant on host responses that do not distinguish bTB from other mycobacteria. We report the presence of a pathogen signature, liparabinomannan (LAM), as a potential biomarker for bTB infection. FINDINGS: Fifty-five animals (uninfected [n?=?33], bTb [n?=?10] and exposed cases [n?=?12]) from a well characterized bovine serum repository were screened for the presence of LAM using a commercially available ELISA. Analysis showed that LAM had a sensitivity of 100% and a specificity of 91.7% for bTB detection (bTB positive versus bTB exposed animals). CONCLUSION: LAM detection easily separated bTB infected animals from bTB exposed and negative controls. We propose that pathogen related markers, such as LAM, should be included with current testing strategies as a battery diagnostic for bTB.
| S-EPMC4152573 | biostudies-literature
Project description:Interleukin (IL)-17A-producing T helper (Th)17 cells are increasingly being acknowledged to be associated with protective immunity to Mycobacterium tuberculosis (Mtb). Subunit vaccines potently promote protective immune responses against Mtb infection that correlate with an expansion of IL-23-dependent Th17 cells. Previous studies revealed that after vaccination, IL-23 is required for protection against challenge with Mtb but the underlying IL-23-dependent-and possibly IL-17A-mediated-mechanisms remain elusive. Therefore, we here analyzed the early outcome of Mtb infection in C57BL/6, IL-23p19-deficient (-/-), and IL-17A-/- mice after vaccination with the subunit vaccine H1-DDA/TDB to investigate the role of the IL-23-Th17 immune axis for the instruction of vaccine-induced protection. While in IL-23p19-/- mice the protective effect was reduced, protection after vaccination was maintained in IL-17A-/- animals for the course of infection of 6 weeks, indicating that after vaccination with H1-DDA/TDB early protection against Mtb is-although dependent on IL-23-not mediated by IL-17A. In contrast, IL-17A deficiency appears to have an impact on maintaining long-term protection. In fact, IL-23 instructed the vaccine-induced memory immunity in the lung, in particular the sustained expansion of tumor necrosis factor (TNF)+IL-2+ multifunctional T cells, independently of IL-17A. Altogether, a targeted induction of IL-23 during vaccination against Mtb might improve the magnitude and quality of vaccine-induced memory immune responses. KEY MESSAGES: After subunit Mtb vaccination with H1-DDA/TDB, IL-23 but not IL-17A contributes to vaccine-induced early protection against infection with Mtb. IL-17F does not compensate for IL-17A deficiency in terms of H1-DDA/TDB-induced protection against Mtb infection. IL 23 promotes the H1-DDA/TDB-induced accumulation of effector memory T cells independently of IL 17A. IL-23 arbitrates the induction of H1-specific IFN-γ-TNF+IL-2+ double-positive multifunctional CD4 T cells after subunit Mtb vaccination in an IL-17A-independent manner.
| S-EPMC8541990 | biostudies-literature
Project description:Bovine tuberculosis (bTB) is caused by Mycobacterium bovis During the early stage of infection, greater than 15% of M. bovis-infected cattle shed mycobacteria through nasal secretions, which can be detected by nested PCR. To compare the differences in the protein profiles of M. bovis-infected cattle that were nested PCR positive (bTBPCR-P) and M. bovis-infected cattle that were nested PCR negative (bTBPCR-N) and to screen for biomarkers that will facilitate the early and accurate detection of bTB, we investigated the protein expression profiles of serum and bovine purified protein derivative (PPD-B)-stimulated plasma among bTBPCR-P (n = 20), bTBPCR-N (n = 20), and uninfected cattle (NC; n = 20) by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2D LC-MS/MS). After comprehensive analysis, we selected 15 putative differentially expressed serum proteins and 15 plasma proteins for validation by parallel reaction monitoring (PRM) with the same cohort used in the iTRAQ analysis. Four serum and five PPD-B-stimulated proteins were confirmed in follow-up enzyme-linked immunosorbent assays. PPD-B-stimulated interleukin 8 (IL-8) displayed the potential to differentiate M. bovis-infected cattle from NC, with an area under the curve (AUC) value of 0.9662, while PPD-B-stimulated C-reactive protein (CRP) displayed the potential to differentiate bTBPCR-P from bTBPCR-N, with an AUC value of 1.00. Finally, double-blind testing with 244 cattle indicated that the PPD-B-stimulated IL-8 test exhibited good agreement with traditional tests (κ > 0.877) with a >90% relative sensitivity and a >98% relative specificity; the PPD-B-stimulated CRP test displayed good agreement with nested PCR (κ = 0.9117), with an observed 94% relative sensitivity and 97% relative specificity. Therefore, the PPD-B-stimulated IL-8 and CRP tests could be used to detect bTB and to differentiate bTBPCR-P from bTBPCR-N.
| S-EPMC6760949 | biostudies-literature
Project description:BackgroundLymphocytes have dichotomous functions in ischemic stroke. Regulatory T cells are protective, while IL-17A from innate lymphocytes promotes the infarct growth. With recent advances of T cell-subtype specific transgenic mouse models it now has become possible to study the complex interplay of T cell subpopulations in ischemic stroke.MethodsIn a murine model of experimental stroke we analyzed the effects of IL-10 on the functional outcome for up to 14 days post-ischemia and defined the source of IL-10 in ischemic brains based on immunohistochemistry, flow cytometry, and bone-marrow chimeric mice. We used neutralizing IL-17A antibodies, intrathecal IL-10 injections, and transgenic mouse models which harbor a deletion of the IL-10R on distinct T cell subpopulations to further explore the interplay between IL-10 and IL-17A pathways in the ischemic brain.ResultsWe demonstrate that IL-10 deficient mice exhibit significantly increased infarct sizes on days 3 and 7 and enlarged brain atrophy and impaired neurological outcome on day 14 following tMCAO. In ischemic brains IL-10 producing immune cells included regulatory T cells, macrophages, and microglia. Neutralization of IL-17A following stroke reversed the worse outcome in IL-10 deficient mice and intracerebral treatment with recombinant IL-10 revealed that IL-10 controlled IL-17A positive lymphocytes in ischemic brains. Importantly, IL-10 acted differentially on αβ and γδ T cells. IL-17A producing CD4+ αβ T cells were directly controlled via their IL-10-receptor (IL-10R), whereas IL-10 by itself had no direct effect on the IL-17A production in γδ T cells. The control of the IL-17A production in γδ T cells depended on an intact IL10R signaling in regulatory T cells (Tregs).ConclusionsTaken together, our data indicate a key function of IL-10 in restricting the detrimental IL-17A-signaling in stroke and further supports that IL-17A is a therapeutic opportunity for stroke treatment.
| S-EPMC8590298 | biostudies-literature
Project description:Interleukin (IL)-17A is a well-described mediator of bone resorption in inflammatory diseases, and postmenopausal osteoporosis is associated with increased serum levels of IL-17A. Ovariectomy (OVX) can be used as a model to study bone loss induced by estrogen deficiency and the role of IL-17A in osteoporosis development has previously been investigated using various methods to inhibit IL-17A signaling in this model. However, the studies show opposing results. While some publications reported IL-17A as a mediator of OVX-induced osteoporosis, others found a bone-protective role for IL-17 receptor signaling. In this study, we provide an explanation for the discrepancies in previous literature and show for the first time that loss of IL-17A has differential effects on OVX-induced osteoporosis; with IL-17A being important for cortical but not trabecular bone loss. Interestingly, the decrease in trabecular bone after OVX in IL-17A knock-out mice, was accompanied by increased adipogenesis depicted by elevated leptin levels. Additionally, the bone marrow adipose tissue expanded, and the bone-turnover decreased in ovariectomized mice lacking IL-17A compared to ovariectomized WT mice. Our results increase the understanding of how IL-17A signaling influences bone remodeling in the different bone compartments, which is of importance for the development of new treatments of post-menopausal osteoporosis.
| S-EPMC7105470 | biostudies-literature
Project description:The term spondyloarthritis (SpA) is used to describe a group of inflammatory autoimmune diseases, including ankylosing spondylitis and psoriatic arthritis, with common genetic risk factors and clinical features. SpA is clinically distinct from rheumatoid arthritis and typically affects the spine, sacroiliac joints, entheses, and, less commonly, peripheral joints. Although the pathogenesis of SpA is not fully understood, recent findings have identified the interleukin (IL)-17 pathway as a key mediator of disease pathogenesis. Clinical evidence for the efficacy of IL-17A inhibition by biologic agents was initially shown in patients with chronic plaque psoriasis, another autoimmune disease mediated by the IL-17 pathway. Subsequently, similar positive efficacy for inhibition of IL-17A was seen in patients with ankylosing spondylitis and psoriatic arthritis. Inhibition of IL-17A may also improve cardiovascular and metabolic comorbidities often found in patients with SpA because studies have linked these disorders to the IL-17 pathway. In this review, we will examine key preclinical studies that demonstrated the mechanistic role of IL-17A in the development SpA and discuss how these observations were translated into clinical practice.
| S-EPMC5341175 | biostudies-literature
Project description:Background & objectives:Psoriasis is a chronic inflammatory skin disease with unknown aetiology. So far studies have confirmed that interleukins, pro-inflammatory factors and T-cell activation play major role in the development of disease. Interleukin-17 (IL-17) a T helper inflammatory cytokine, was found to be positively correlated with severity of psoriasis. However, the specific mechanism has not been clarified. IL-17A and IL-17F are group members of IL17 family cytokines and found to be located adjacent to one another on the same human chromosome, 6p12. The present study was designed to identify the association between IL-17A and IL-17F gene polymorphism with susceptibility of psoriasis in north Indian population. Methods:A total of 166 psoriasis patients and 150 healthy controls were genotyped for IL-17A and IL-17F gene polymorphism by amplification refractory mutation system-polymerase chain reaction method. One single nucleotide polymorphism (SNP) was analysed in IL-17A (rs10484879) and one SNP in IL-17F (rs763780) to look for an association with psoriasis. Results:Our study indicated decreased frequency of IL-17A (rs10484879) G allele (51.8 vs. 65.0%), and IL-17F (rs763780) C allele (36.5 vs. 45.7%) in psoriatic patients as compared to healthy controls. Interpretation & conclusions:The present findings suggest that IL-17A (rs10484879) G/T and IL-17F (rs763780) C/T gene polymorphisms may contribute in pathogenesis of psoriasis. Further studies need to be done to confirm these findings.
| S-EPMC6362716 | biostudies-literature