ArticleVeterinary research2018
A Mycobacterium avium subsp. paratuberculosis relA deletion mutant and a 35 kDa major membrane protein elicit development of cytotoxic T lymphocytes with ability to kill intracellular bacteria.
Article in Veterinary research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Advances and Challenges in Mycobacterial Genetic Engineering: Techniques for Knockout, Knockdown and Overexpression.Journal of microbiology and biotechnology · 2025Review
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- Evaluation of alternative vaccination routes against paratuberculosis in goats.Frontiers in veterinary science · 2024Article
- Use of RNA-seq to identify genes encoding cytokines and chemokines activated following uptake and processing a candidate peptide vaccine developed againstBrazilian journal of veterinary medicine · 2024Article
- Modeling Paratuberculosis in Laboratory Animals, Cells, or Tissues: A Focus on Their Applications for Pathogenesis, Diagnosis, Vaccines, and Therapy Studies.Animals : an open access journal from MDPI · 2023Review
- Evaluation ofFrontiers in cellular and infection microbiology · 2023Article
- Immunogenicity and efficacy of an oral live-attenuated vaccine for bovine Johne's disease.Frontiers in immunology · 2023Article
- Review
- Advances in Understanding of the Immune Response to Mycobacterial Pathogens and Vaccines through Use of Cattle andVaccines · 2021Review
- Article
- Flow Cytometric Analysis of the Cytotoxic T-Cell Recall Response toVeterinary sciences · 2021Article
- Article
- Immunoinformatic-Based Prediction of Candidate Epitopes for the Diagnosis and Control of Paratuberculosis (Johne's Disease).Pathogens (Basel, Switzerland) · 2020Article
- Mycobacterium avium paratuberculosis and Mycobacterium avium complex and related subspecies as causative agents of zoonotic and occupational diseases.Journal of cellular physiology · 2019Review
- Baseballs, tennis balls, livestock farm manure, the IDH1 mutation, endothelial cell proliferation and hypoxic pseudopalisading (granulomatous) necrosis:Open veterinary journal · 2019Review
- Capacity to Elicit Cytotoxic CD8 T Cell Activity AgainstFrontiers in immunology · 2019Article
- Bovine DerivedFrontiers in immunology · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Efforts to develop live attenuated vaccines against Mycobacterium avium subspecies paratuberculosis (Map), using indirect methods to screen Map deletion mutants for potential efficacy, have not been successful. A reduction in the capacity to survive in macrophages has not predicted the ability of mutants to survive in vivo. Previous studies for screening of three deletion mutants in cattle and goats revealed one mutant, with a deletion in relA (ΔMap/relA), could not establish a persistent infection. Further studies, using antigen presenting cells (APC), blood dendritic cells and monocyte derived DC, pulsed with ΔMap/relA or a 35 kDa Map membrane protein (MMP) revealed a component of the response to ΔMap/relA was directed towards MMP. As reported herein, we developed a bacterium viability assay and cell culture assays for analysis and evaluation of cytotoxic T cells generated against ΔMap/relA or MMP. Analysis of the effector activity of responding cells revealed the reason ΔMap/relA could not establish a persistent infection was that vaccination elicited development of cytotoxic CD8 T cells (CTL) with the capacity to kill intracellular bacteria. We demonstrated the same CTL response could be elicited with two rounds of antigenic stimulation of APC pulsed with ΔMap/relA or MMP ex vivo. Cytotoxicity was mediated through the perforin granzyme B pathway. Finally, cognate recognition of peptides presented in context of MHC I and II molecules to CD4 and CD8 T cells is required for development of CTL.
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Registered trials
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.