ArticlePLoS computational biology2014
Competition for antigen between Th1 and Th2 responses determines the timing of the immune response switch during Mycobaterium avium subspecies paratuberulosis infection in ruminants.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
29 citing papers in PubMed, 58 citations in OpenAlex.
- A Longitudinal Study ofAnimals : an open access journal from MDPI · 2026Article
- Advances in paratuberculosis research and control: a comprehensive expert review.BMC veterinary research · 2026Review
- Coinfection with malaria alters the fecundity and within-host persistence of an intestinal nematode.PLoS neglected tropical diseases · 2026Article
- Use of ELISA to predict highJournal of veterinary research · 2026Article
- A Modified Variant ofVaccines · 2025Article
- Antibodies and Inflammation: Fecal Biomarkers of Gut Health in Domestic Ruminants.Journal of experimental zoology. Part A, Ecological and integrative physiology · 2025Article
- An Aedes-Anopheles Vaccine Candidate Supplemented with BCG Epitopes Against the Aedes and Anopheles Genera to Overcome Hypersensitivity to Mosquito Bites.Acta parasitologica · 2024Article
- Article
- Stage of infection withFrontiers in veterinary science · 2023Article
- Advantages and Challenges of Differential Immune Cell Count Determination in Blood and Milk for Monitoring the Health and Well-Being of Dairy Cows.Veterinary sciences · 2022Review
- An Embedded Multiscale Modelling to Guide Control and Elimination of Paratuberculosis in Ruminants.Computational and mathematical methods in medicine · 2021Article
- Tape-Strip Proteomic Profiling of Atopic Dermatitis on Dupilumab Identifies Minimally Invasive Biomarkers.Frontiers in immunology · 2020Article
- Transcriptome Profiling of Bovine Macrophages Infected byFrontiers in immunology · 2019Article
- CD4Frontiers in pediatrics · 2019Article
- Resilience to infection by Mycobacterium avium subspecies paratuberculosis following direct intestinal inoculation in calves.Veterinary research · 2018Article
- Biomarkers for Early Stages of Johne's Disease Infection and Immunization in Goats.Frontiers in microbiology · 2018Article
- MAP1981c, a Putative Nucleic Acid-Binding Protein, Produced byFrontiers in cellular and infection microbiology · 2018Article
- Inferring biomarkers for Mycobacterium avium subsp. paratuberculosis infection and disease progression in cattle using experimental data.Scientific reports · 2017Article
- Article
- Development of vaccines to Mycobacterium avium subsp. paratuberculosis infection.Clinical and experimental vaccine research · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Johne's disease (JD), a persistent and slow progressing infection of ruminants such as cows and sheep, is caused by slow replicating bacilli Mycobacterium avium subspecies paratuberculosis (MAP) infecting macrophages in the gut. Infected animals initially mount a cell-mediated CD4 T cell response against MAP which is characterized by the production of interferon gamma (Th1 response). Over time, Th1 response diminishes in most animals and antibody response to MAP antigens becomes dominant (Th2 response). The switch from Th1 to Th2 response occurs concomitantly with disease progression and shedding of the bacteria in feces. Mechanisms controlling this Th1/Th2 switch remain poorly understood. Because Th1 and Th2 responses are known to cross-inhibit each other, it is unclear why initially strong Th1 response is lost over time. Using a novel mathematical model of the immune response to MAP infection we show that the ability of extracellular bacteria to persist outside of macrophages naturally leads to switch of the cellular response to antibody production. Several additional mechanisms may also contribute to the timing of the Th1/Th2 switch including the rate of proliferation of Th1/Th2 responses at the site of infection, efficiency at which immune responses cross-inhibit each other, and the rate at which Th1 response becomes exhausted over time. Our basic model reasonably well explains four different kinetic patterns of the Th1/Th2 responses in MAP-infected sheep by variability in the initial bacterial dose and the efficiency of the MAP-specific T cell responses. Taken together, our novel mathematical model identifies factors of bacterial and host origin that drive kinetics of the immune response to MAP and provides the basis for testing the impact of vaccination or early treatment on the duration of infection.
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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.