ArticleInfection and immunity2007
Impaired expression of perforin and granulysin in CD8+ T cells at the site of infection in human chronic pulmonary tuberculosis.
Article in Infection and immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 105 citations in OpenAlex.
- Immune endotypes in tuberculosis: Keys to decoding disease complexity.Journal of internal medicine · 2026Review
- mRNA vaccine development for tuberculosis: antigen design, immune mechanisms, and translational challenges.Archives of microbiology · 2026Review
- Protection against reinfection with Mycobacterium tuberculosis extends across heterologous Mtb lineages.Mucosal immunology · 2026Article
- CD8+ lymphocytes in immunity against tuberculosis.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- T cell-macrophage interactions in tuberculosis: What we've got here is failure to communicate.Journal of internal medicine · 2026Review
- Cytotoxic granules and effector molecules from immune cells in tuberculosis: Mechanisms of host defense and therapeutic potential.Virulence · 2025Review
- Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis.European journal of immunology · 2025Article
- Antimycobacterial and immunomodulatory activities of sorafenib in a preclinical mouse model of TB infection through CD4Frontiers in immunology · 2025Article
- Article
- A Key Role of CD8+ T Cells in Controlling of Tuberculosis Infection.Diagnostics (Basel, Switzerland) · 2023Article
- Molecular Markers of Early Immune Response in Tuberculosis: Prospects of Application in Predictive Medicine.International journal of molecular sciences · 2023Review
- Article
- Immunosuppressive Features of the Microenvironment in Lymph Nodes Granulomas from Tuberculosis and HIV-Co-Infected Patients.The American journal of pathology · 2022Article
- Transcriptional Profiling of Early and Late Phases of Bovine Tuberculosis.Infection and immunity · 2022Article
- Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field.Frontiers in immunology · 2022Review
- The Role of Gut and Lung Microbiota in Susceptibility to Tuberculosis.International journal of environmental research and public health · 2021Review
- Slow radiological improvement and persistent low-grade inflammation after chemotherapy in tuberculosis patients with type 2 diabetes.BMC infectious diseases · 2020Observational
- Diverse immune environments in human lung tuberculosis granulomas assessed by quantitative multiplexed immunofluorescence.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2020Article
- Diagnostic performance of culture filtered protein 10-specific perforin in pediatric patients with active tuberculosis.Journal of clinical laboratory analysis · 2020Article
- Coordinated In Vitro Release of Granulysin, Perforin and IFN-γ in TB and HIV/TB Co-Infection Associated with Clinical Outcomes before and after Anti-TB Treatment.Pathogens (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Protective immunity in tuberculosis is dependent on the coordinated release of cytolytic effector molecules from effector T cells and the subsequent granule-associated killing of infected target cells. In this study, we investigated the expression of cytolytic (perforin and granzyme A) and antimicrobial (granulysin) molecules at the single-cell level in cryopreserved lung tissue from patients with chronic, progressive tuberculosis disease. Quantification of protein-expressing cells was performed by in situ imaging, while mRNA levels in the infected tissue were analyzed by real-time PCR. Persistent inflammation, including excessive expression of inducible nitric oxide synthase in CD68+ macrophages and significant infiltration of CD3+, CD8+ and CD4+ T cells, was evident in tuberculosis lesions in all patients. However, despite the accumulation of CD3+ T cells, perforin- and granulysin-expressing CD3+ T cells were detected at two- to threefold-lower ratios in the tuberculosis lesions than in distal lung parenchyma and uninfected control lungs, respectively. This was evident at both the protein and mRNA levels. Moreover, perforin- and granulysin-expressing CD8+ T cells were scarce in individual granulomas within the tuberculosis lesions. In contrast, significant up-regulation of granzyme A-expressing CD3+ T cells was evident in the lesions from all patients. Confocal microscopy revealed coexpression of perforin and granulysin, primarily in CD8+ T cells; however, this expression was lower in the tuberculosis lesions. These findings suggest that symptomatic, chronic tuberculosis disease is associated with insufficient up-regulation of perforin and granulysin coexpression in CD8+ T cells at the local site of infection.
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