ArticleProceedings of the National Academy of Sciences of the United States of America2001
Virulence of a Mycobacterium tuberculosis clinical isolate in mice is determined by failure to induce Th1 type immunity and is associated with induction of IFN-alpha /beta.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 316 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
316 citing papers in PubMed, 599 citations in OpenAlex.
- Safety and Immunogenicity of the Recombinant BCG Vaccine AERAS-422 in Healthy BCG-naïve Adults: A Randomized, Active-controlled, First-in-human Phase 1 Trial.EBioMedicine · 2016Trial
- Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.Cell host & microbe · 2026Article
- Article
- Modulation of Ferroptosis During EarlybioRxiv : the preprint server for biology · 2026Article
- EsxN drives ISG15-mediated dsDNA release to activate cGAS-STING signaling and promote mycobacterial survival.Microbiology spectrum · 2026Article
- Contribution of cytotoxic CD8 T cells, neutrophils and type 1 interferon signaling to hyperinflammation in HIV-associated TB meningitis.bioRxiv : the preprint server for biology · 2026Article
- Polymorphisms in IRF3 exon 1 influence the immune response to Brucella infection in small ruminants.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Toxoplasma gondii GRA3 activates interferon-stimulated genes and STAT6 by the cGAS-STING pathway to promote parasite proliferation.PLoS neglected tropical diseases · 2026Article
- Strong sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis susceptibility.bioRxiv : the preprint server for biology · 2026Article
- Inflammasome Activation Differences Underpin DifferentMedComm · 2025Article
- Mycobacterial ESAT-6 triggers cGAS-STING pathway via the GSDMD-NT dependent mitochondria dysfunction.Virulence · 2025Article
- Article
- Global trends and hotspots of tumor necrosis factor-alpha in pulmonary tuberculosis: a bibliometric and visualization analysis.Journal of thoracic disease · 2025Article
- Interferons in health and disease.Cell · 2025Review
- Host-intrinsic and host-extrinsic factors modulate immunity to Mtb infection, reinfection, and noncanonical vaccination routes.Cell reports. Medicine · 2025Review
- Export of eDNA is a mechanism used by Mycobacterium avium subsp. hominissuis for survival within host macrophages.Archives of microbiology · 2025Article
- Myeloid cell genome-wide screen identifies variants associated with Mycobacterium tuberculosis-induced cytokine transcriptional responses.The Journal of clinical investigation · 2025Article
- The Role of Type I Interferons in Tuberculosis and in Tuberculosis-Risk-Associated Comorbidities.Infectious disease reports · 2025Review
- Loss of theScience advances · 2025Article
- Deconvoluting the interplay of innate and adaptive immunity in BCG-induced nonspecific and TB-specific host resistance.The Journal of experimental medicine · 2025Review
256 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
To understand how virulent mycobacteria subvert host immunity and establish disease, we examined the differential response of mice to infection with various human outbreak Mycobacterium tuberculosis clinical isolates. One clinical isolate, HN878, was found to be hypervirulent, as demonstrated by unusually early death of infected immune-competent mice, compared with infection with other clinical isolates. The differential effect on survival required lymphocyte function because severe combined immunodeficiency (SCID) mice infected with HN878 or other clinical isolates all died at the same rate. The hypervirulence of HN878 was associated with failure to induce M. tuberculosis-specific proliferation and IFN-gamma production by spleen and lymph node cells from infected mice. In addition, 2- to 4-fold lower levels of tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-12, and IFN-gamma mRNAs were observed in lungs of HN878-infected mice. IL-10, IL-4, and IL-5 mRNA levels were not significantly elevated in lungs of HN878 infected mice. In contrast, IFN-alpha mRNA levels were significantly higher in lungs of these mice. To further investigate the role of Type 1 IFNs, mice infected with HN878 were treated intranasally with purified IFN-alpha/beta. The treatment resulted in increased lung bacillary loads and even further reduced survival. These results suggest that the hypervirulence of HN878 may be due to failure of this strain to stimulate Th1 type immunity. In addition, the lack of development of Th1 immunity in response to HN878 appears to be associated with increased induction of Type 1 IFNs.
Indexed as
Identifiers
What OpenQuestion holds
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.