Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists.
Abstract: Our understanding of the innate immune response in the horse has been limited by a lack of definitive data concerning cell signaling in response to microbial products. Toll-like receptors (TLRs) recognize conserved molecular motifs of microbes and elicit immune responses through their coupling with intracellular adaptor molecules, particularly MyD88 and TRIF. To provide a more definitive characterization of TLR signaling in the horse, the objectives of this study were to: (1) characterize the responses of equine monocytes to TLR ligands that signal through MyD88, TRIF or both in other species, and (2) determine the profiles of gene expression initiated utilizing these adaptor molecules. Monocytes were used to establish concentration response curves for Escherichia coli lipopolysaccharide (LPS; TLR4 ligand) and N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-[R]-cysteinyl-[S]-seryl-[S]-lysyl-[S]-lysyl-[S]-lysyl-[S]-lysine x 3 HCl (Pam(3)CSK(4); TLR2 ligand) based on expression of procoagulant activity (PCA) and production of tumor necrosis factor-alpha (TNF-alpha); effects of polyinosine-polycytidylic acid (Poly I:C; TLR3 ligand) were determined by quantifying expression of mRNA for interferon-beta (IFN-ss). Expression of genes associated with the MyD88- (TNF-alpha, IL-1ss, IL-6 and IL-10) and TRIF-dependent pathways (IFN-ss, IP-10, RANTES and TRAF1) were measured at intervals spanning 20 h. LPS and Pam(3)CSK(4) induced significantly higher expression of TNF-alpha, IL-1ss, and IL-10 than did Poly I:C. Poly I:C induced significantly higher expression of IFN-ss, IP-10 and RANTES than did either the TLR2 or TLR4 ligands. High concentrations of E. coli LPS did not significantly increase expression of genes associated with the TRIF-dependent pathway. The results of this study suggest that equine monocytes utilize a common intracellular pathway in response to TLR2 and TLR4 ligands, but a distinct pathway in response to TLR3 ligands.
Publication Date: 2008-10-11 PubMed ID: 19019456DOI: 10.1016/j.vetimm.2008.09.028Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This research article explores the different ways in which equine monocytes, a type of immune cell in horses, respond to different microbial threats. It specifically looks at how these cells use different signaling pathways, namely MyD88 and TRIF, in response to activators of the Toll-like receptors (TLRs), which are integral to the immune response.
Background and Objectives
- The study aimed to extend our understanding of the immune response in horses by clarifying how their cells react to microbial threats using different signaling pathways – MyD88 and TRIF. Previous information in this area for horses was limited and unclear.
- The objectives included understanding how equine monocytes respond to different TLR ligands (molecules that can bind to a protein) and exploring how gene expression changes following the utilization of the MyD88 and TRIF adaptors.
Methodology
- The researchers used monocytes (a type of white blood cell) and various TLR ligands, including Escherichia coli lipopolysaccharide (LPS; TLR4 ligand), N-palmitoyl-S-[2,3-bis (palmitoyloxy) – (2RS) -propyl] – [R] – cysteinyl – [S] -seryl – [S] – lysyl-[S]-lysyl-[S]-lysine x 3 HCl (Pam(3)CSK(4); TLR2 ligand), and polyinosine-polycytidylic acid (Poly I: C; TLR3 ligand).
- The responses of the monocytes were evaluated based on the expression of procoagulant activity (PCA) and the production of tumor necrosis factor-alpha (TNF-alpha).
- Gene expression associated with the MyD88 and TRIF pathways over a 20-hour period were checked using mRNA expression.
Findings
- TNF-alpha, IL-1ss, and IL-10 – genes associated with the MyD88 pathway – showed significantly higher expression in response to LPS and Pam(3)CSK(4) (TLR2 and TLR4 ligands, respectively) than Poly I: C (TLR3 ligand).
- IFN-ss, IP-10, and RANTES – genes associated with the TRIF-dependent pathway –were expressed significantly more in response to Poly I: C, compared to the TLR2 and TLR4 ligands.
- High concentrations of E. coli LPS did not significantly increase expression of genes associated with the TRIF-dependent pathway.
Conclusion
- The study demonstrated that equine monocytes utilize different cellular pathways in response to different TLR ligands, suggesting that these cells use a common intracellular pathway in response to TLR2 and TLR4 ligands, but use a distinct pathway when responding to TLR3 ligands.
Cite This Article
APA
Figueiredo MD, Vandenplas ML, Hurley DJ, Moore JN.
(2008).
Differential induction of MyD88- and TRIF-dependent pathways in equine monocytes by Toll-like receptor agonists.
Vet Immunol Immunopathol, 127(1-2), 125-134.
https://doi.org/10.1016/j.vetimm.2008.09.028 Publication
Researcher Affiliations
- Department of Large Animal Medicine, College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7385, USA. mf239@uga.edu
MeSH Terms
- Adaptor Proteins, Vesicular Transport / metabolism
- Animals
- Base Sequence
- Chemokine CCL5 / genetics
- Chemokine CXCL10 / genetics
- Cytokines / genetics
- DNA Primers / genetics
- Gene Expression Profiling
- Horses / genetics
- Horses / immunology
- Horses / metabolism
- In Vitro Techniques
- Interferon-gamma / genetics
- Ligands
- Lipopeptides / pharmacology
- Lipopolysaccharides / pharmacology
- Monocytes / drug effects
- Monocytes / immunology
- Monocytes / metabolism
- Myeloid Differentiation Factor 88 / metabolism
- Poly I-C / pharmacology
- RNA, Messenger / genetics
- RNA, Messenger / metabolism
- Signal Transduction / drug effects
- Toll-Like Receptors / agonists
- Tumor Necrosis Factor-alpha / biosynthesis
- Tumor Necrosis Factor-alpha / genetics
Citations
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