ArticleInfection and immunity2013
Altered Toll-like receptor 9 signaling in Mycobacterium avium subsp. paratuberculosis-infected bovine monocytes reveals potential therapeutic targets.
Article in Infection and immunity, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Paratuberculosis: a mucosal immunology perspective.Frontiers in immunology · 2026Review
- Latent microbial infections leading to myelin and axonal damage in multiple sclerosis: A narrative review.Current journal of neurology · 2024Article
- Bovine Immunity and Vitamin DMicroorganisms · 2022Review
- Signaling differences in peripheral blood mononuclear cells of high and low vaccine responders prior to, and following, vaccination in piglets.Vaccine: X · 2022Article
- A Progressive Loss of phosphoSer138-Profilin Aligns with Symptomatic Course in the R6/2 Mouse Model of Huntington's Disease: Possible Sex-Dependent Signaling.Cellular and molecular neurobiology · 2022Article
- Kinome Analysis of Cattle Peripheral Lymph Nodes to Elucidate Differential Response toMicroorganisms · 2022Article
- Effects of 1,25-Dihydroxyvitamin DFrontiers in veterinary science · 2022Article
- Using Omics Approaches in the Discovery of Biomarkers for Early Diagnosis of Johne's Disease in Sheep and Goats.Animals : an open access journal from MDPI · 2021Review
- TLRs in Mycobacterial Pathogenesis: Black and White or Shades of Gray.Current microbiology · 2021Review
- Exogenous Vitamin DFrontiers in cellular and infection microbiology · 2021Article
- Identification of Long Non-coding RNA Isolated From Naturally Infected Macrophages and Associated With Bovine Johne's Disease in Canadian Holstein Using a Combination of Neural Networks and Logistic Regression.Frontiers in veterinary science · 2021Article
- Kinome profiling of peripheral blood mononuclear cells collected prior to vaccination reveals biomarkers and potential mechanisms of vaccine unresponsiveness in pigs.Scientific reports · 2020Article
- Effects of Mesobiliverdin IXα-Enriched Microalgae Feed on Gut Health and Microbiota of Broilers.Frontiers in veterinary science · 2020Article
- From Beef to Bees: High-Throughput Kinome Analysis to Understand Host Responses of Livestock Species to Infectious Diseases and Industry-Associated Stress.Frontiers in immunology · 2020Review
- Methods and approaches to disease mechanisms using systems kinomics.Synthetic and systems biotechnology · 2018Review
- Bacteria-Host Interactions in Multiple Sclerosis.Frontiers in microbiology · 2018Review
- Syrian Hamsters as a Small Animal Model for Emerging Infectious Diseases: Advances in Immunologic Methods.Advances in experimental medicine and biology · 2017Article
- Proteomic discovery of host kinase signaling in bacterial infections.Proteomics. Clinical applications · 2016Review
- Models and Methods to Investigate Acute Stress Responses in Cattle.Animals : an open access journal from MDPI · 2015Article
- Characterization of the host response to pichinde virus infection in the Syrian golden hamster by species-specific kinome analysis.Molecular & cellular proteomics : MCP · 2015Article
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterium avium subsp. paratuberculosis is the causative agent of Johne's disease in cattle. The complex, multifaceted interaction of M. avium subsp. paratuberculosis with its host includes dampening the ability of infected cells to respond to stimuli that promote M. avium subsp. paratuberculosis clearance. By disrupting host defenses, M. avium subsp. paratuberculosis creates an intracellular environment that favors the establishment and maintenance of infection. Toll-like receptors (TLRs) are important sensors that initiate innate immune responses to microbial challenge and are also immunotherapeutic targets. For example, TLR9 contributes to host defense against M. avium subsp. paratuberculosis, and its agonists (CpG oligodeoxynucleotides [ODNs]) are under investigation for treatment of Johne's disease and other infections. Here we demonstrate that M. avium subsp. paratuberculosis infection changes the responsiveness of bovine monocytes to TLR9 stimulation. M. avium subsp. paratuberculosis inhibits classical TLR9-mediated responses despite a 10-fold increase in TLR9 expression and maintained uptake of CpG ODNs. Other TLR9-mediated responses, such as oxidative burst, which occur through noncanonical signaling, remain functional. Kinome analysis verifies that classic TLR9 signaling is blocked by M. avium subsp. paratuberculosis infection and that signaling instead proceeds through a Pyk2-mediated mechanism. Pyk2-mediated signaling does not hinder infection, as CpG ODNs fail to promote M. avium subsp. paratuberculosis clearance. Indeed, Pyk2 signaling appears to be an important aspect of M. avium subsp. paratuberculosis infection, as Pyk2 inhibitors significantly reduce the number of intracellular M. avium subsp. paratuberculosis bacteria. The actions of M. avium subsp. paratuberculosis on TLR9 signaling may represent a strategy to generate a host environment which is better suited for infection, revealing potential new targets for therapeutic intervention.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.