ArticlePLoS pathogens2020
SIV and Mycobacterium tuberculosis synergy within the granuloma accelerates the reactivation pattern of latent tuberculosis.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Population-level genome sequencing reveals distinctmSystems · 2026Article
- Modulation of pulmonary IL-21 expression during latent TB and M. tuberculosis/SIV coinfection.JCI insight · 2026Article
- The host immune response to Mycobacterium tuberculosis determining protection or disease progression.Nature immunology · 2026Review
- Population-level genome sequencing reveals distinct Mycobacterium tuberculosis intrahost mutational trajectories in simian immunodeficiency virus co-infected and antiretroviral treated non-human primates.bioRxiv : the preprint server for biology · 2026Article
- Antiretroviral treatment does not prevent extrapulmonary tuberculosis during SIV/Mtb coinfection in macaques.JCI insight · 2026Article
- Protection against reinfection with Mycobacterium tuberculosis extends across heterologous Mtb lineages.Mucosal immunology · 2026Article
- Distinct mechanisms drive post-antibiotic Tuberculosis relapse post-cure versus post-treatment-failure.bioRxiv : the preprint server for biology · 2026Article
- Viral control is required for intravenous BCG-mediated protection against tuberculosis in simian immunodeficiency virus-infected macaques.Research square · 2025Article
- Characterizing PET CT patterns and bacterial dissemination features of tuberculosis relapse in the macaque model.Infection and immunity · 2025Article
- Adapting systems biology to address the complexity of human disease in the single-cell era.Nature reviews. Genetics · 2025Review
- The Impact of Animal Models and Strain Standardization on the Evaluation of Tuberculosis Vaccine Efficacy.Vaccines · 2025Review
- PET imaging of mycobacterial infection: transforming the pipeline for tuberculosis drug development.Npj imaging · 2025Review
- Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes.The Journal of experimental medicine · 2025Article
- Markov field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques.Cell systems · 2024Article
- Deciphering lung granulomas in HIV & TB co-infection: unveiling macrophages aggregation with IL6R/STAT3 activation.Emerging microbes & infections · 2024Article
- Markov Field network model of multi-modal data predicts effects of immune system perturbations on intravenous BCG vaccination in macaques.bioRxiv : the preprint server for biology · 2024Article
- CD4Immunity · 2024Article
- CD4 T cells and CD8α+ lymphocytes are necessary for intravenous BCG-induced protection against tuberculosis in macaques.bioRxiv : the preprint server for biology · 2024Article
- CD4bioRxiv : the preprint server for biology · 2023Article
- Immune Responses in Lung Granulomas during Mtb/HIV Co-Infection: Implications for Pathogenesis and Therapy.Pathogens (Basel, Switzerland) · 2023Review
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Human immunodeficiency virus infection is the most common risk factor for severe forms of tuberculosis (TB), regardless of CD4 T cell count. Using a well-characterized cynomolgus macaque model of human TB, we compared radiographic, immunologic and microbiologic characteristics of early (subclinical) reactivation of latent M. tuberculosis (Mtb) infection among animals subsequently infected with simian immunodeficiency virus (SIV) or who underwent anti-CD4 depletion by a depletion antibody. CD4 depleted animals had significantly fewer CD4 T cells within granulomas compared to Mtb/SIV co-infected and Mtb-only control animals. After 2 months of treatment, subclinical reactivation occurred at similar rates among CD4 depleted (5 of 7 animals) and SIV infected animals (4 of 8 animals). However, SIV-induced reactivation was associated with more dissemination of lung granulomas that were permissive to Mtb growth resulting in greater bacterial burden within granulomas compared to CD4 depleted reactivators. Granulomas from Mtb/SIV animals displayed a more robust T cell activation profile (IFN-α, IFN-γ, TNF, IL-17, IL-2, IL-10, IL-4 and granzyme B) compared to CD4 depleted animals and controls though these effectors did not protect against reactivation or dissemination, but instead may be related to increased viral and/or Mtb antigens. SIV replication within the granuloma was associated with reactivation, greater overall Mtb growth and reduced Mtb killing resulting in greater overall Mtb burden. These data support that SIV disrupts protective immune responses against latent Mtb infection beyond the loss of CD4 T cells, and that synergy between SIV and Mtb occurs within granulomas.
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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.