The immunology of tuberculosis: From bench to bedside

Tuberculosis (TB) is an international public health priority and kills almost two million people annually. TB is out of control in Africa due to increasing poverty and HIV coinfection, and drug‐resistant TB threatens to destabilize TB control efforts in several regions of the world. Existing diagnostic tools and therapeutic interventions for TB are suboptimal. Thus, new vaccines, immunotherapeutic interventions and diagnostic tools are urgently required to facilitate TB control efforts. An improved understanding of the immunopathogenesis of TB can facilitate the identification of correlates of immune protection, the design of effective vaccines, the rational selection of immunotherapeutic agents, the evaluation of new drug candidates, and drive the development of new immunodiagnostic tools. Here we review the immunology of TB with a focus on aspects that are clinically and therapeutically relevant. An immunologically orientated approach to tackling TB can only succeed with concurrent efforts to alleviate poverty and reduce the global burden of HIV.

[1]  Alimuddin Zumla,et al.  Feasibility and Diagnostic Utility of Antigen-Specific Interferon-γ Responses for Rapid Immunodiagnosis of Tuberculosis Using Induced Sputum , 2010, PloS one.

[2]  M. Pai Spectrum of latent tuberculosis — existing tests cannot resolve the underlying phenotypes , 2010, Nature Reviews Microbiology.

[3]  G. Kaplan,et al.  Advances in immunotherapy for tuberculosis treatment. , 2009, Clinics in chest medicine.

[4]  S. Choi,et al.  Diagnosis of abdominal tuberculosis by T-cell-based assays on peripheral blood and peritoneal fluid mononuclear cells. , 2009, The Journal of infection.

[5]  J. Casanova,et al.  Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis , 2009, The Journal of experimental medicine.

[6]  C. Weber,et al.  Neutrophil granule proteins tune monocytic cell function. , 2009, Trends in immunology.

[7]  J. Flynn,et al.  The spectrum of latent tuberculosis: rethinking the biology and intervention strategies , 2009, Nature Reviews Microbiology.

[8]  R. Eberhardt,et al.  Bronchoalveolar lavage enzyme-linked immunospot for a rapid diagnosis of tuberculosis: a Tuberculosis Network European Trialsgroup study. , 2009, American journal of respiratory and critical care medicine.

[9]  M. Veldhoen,et al.  Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. , 2009, Immunity.

[10]  Mi‐jeong Kim,et al.  Foamy macrophages and the progression of the human tuberculosis granuloma , 2009, Nature Immunology.

[11]  S. Kaufmann,et al.  Fine-tuning of T cell responses during infection. , 2009, Current opinion in immunology.

[12]  G. Bjune,et al.  The protective role of antibody responses during Mycobacterium tuberculosis infection , 2009, Clinical and experimental immunology.

[13]  A. Diacon,et al.  Differential cytokine/chemokines and KL-6 profiles in patients with different forms of tuberculosis. , 2009, Cytokine.

[14]  S. Kaufmann,et al.  Novel recombinant BCG expressing perfringolysin O and the over-expression of key immunodominant antigens; pre-clinical characterization, safety and protection against challenge with Mycobacterium tuberculosis. , 2009, Vaccine.

[15]  E. Bateman,et al.  Quantitative lung T cell responses aid the rapid diagnosis of pulmonary tuberculosis , 2009, Thorax.

[16]  H. Bang,et al.  Tuberculosis Is Associated with a Down-Modulatory Lung Immune Response That Impairs Th1-Type Immunity1 , 2009, The Journal of Immunology.

[17]  B. Ryffel,et al.  TLR2-dependent mast cell activation contributes to the control of Mycobacterium tuberculosis infection. , 2009, Microbes and infection.

[18]  E. Bateman,et al.  Within-subject variability and boosting of T-cell interferon-gamma responses after tuberculin skin testing. , 2009, American journal of respiratory and critical care medicine.

[19]  P. Andersen,et al.  Tuberculosis Subunit Vaccination Provides Long-Term Protective Immunity Characterized by Multifunctional CD4 Memory T Cells1 , 2009, The Journal of Immunology.

[20]  P. Saha,et al.  FoxP3+ regulatory T cells suppress effector T-cell function at pathologic site in miliary tuberculosis. , 2009, American journal of respiratory and critical care medicine.

[21]  R. Casetti,et al.  Characterization of regulatory T cells identified as CD4+CD25highCD39+ in patients with active tuberculosis , 2009, Clinical and experimental immunology.

[22]  M. Brennan,et al.  Tuberculosis vaccine research: the impact of immunology. , 2009, Current opinion in immunology.

[23]  R. Hussain,et al.  Dynamic Changes in Biomarker Profiles Associated with Clinical and Subclinical Tuberculosis in a High Transmission Setting: A Four‐Year Follow‐Up Study , 2009, Scandinavian journal of immunology.

[24]  C. Antoni,et al.  Anti-TNF immunotherapy reduces CD8+ T cell-mediated antimicrobial activity against Mycobacterium tuberculosis in humans. , 2009, The Journal of clinical investigation.

[25]  J. Dietrich,et al.  Interaction of Mycobacterium tuberculosis with the host: consequences for vaccine development , 2009, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[26]  M. Pai,et al.  T-cell interferon-γ release assays for the rapid immunodiagnosis of tuberculosis: clinical utility in high-burden vs. low-burden settings , 2009, Current opinion in pulmonary medicine.

[27]  Robert J Wilkinson,et al.  Eliminating latent tuberculosis. , 2009, Trends in microbiology.

[28]  Alimuddin Zumla,et al.  Biomarkers for tuberculosis disease status and diagnosis , 2009, Current opinion in pulmonary medicine.

[29]  F. Cobelens,et al.  LTBI: latent tuberculosis infection or lasting immune responses to M. tuberculosis? A TBNET consensus statement , 2009, European Respiratory Journal.

[30]  E. Bateman,et al.  Utility of quantitative T-cell responses versus unstimulated interferon-γ for the diagnosis of pleural tuberculosis , 2009, European Respiratory Journal.

[31]  R. Liblau,et al.  Invariant NKT cells inhibit development of the Th17 lineage , 2009, Proceedings of the National Academy of Sciences.

[32]  G. Kaplan,et al.  HIV-1 infection in infants severely impairs the immune response induced by Bacille Calmette-Guérin vaccine. , 2009, The Journal of infectious diseases.

[33]  A. Cooper,et al.  Cell-mediated immune responses in tuberculosis. , 2009, Annual review of immunology.

[34]  Sung Goo Park,et al.  NADPH Oxidase 2 Interaction with TLR2 Is Required for Efficient Innate Immune Responses to Mycobacteria via Cathelicidin Expression1 , 2009, The Journal of Immunology.

[35]  J. Chan,et al.  How B cells shape the immune response against Mycobacterium tuberculosis , 2009, European journal of immunology.

[36]  R. Wilkinson,et al.  Association between tuberculin skin test reactivity, the memory CD4 cell subset, and circulating FoxP3-expressing cells in HIV-infected persons. , 2009, The Journal of infectious diseases.

[37]  P. Ravn,et al.  IP-10, MCP-1, MCP-2, MCP-3, and IL-1RA hold promise as biomarkers for infection with M. tuberculosis in a whole blood based T-cell assay , 2009, BMC Research Notes.

[38]  R. Wallis Mycobacterial disease attributable to tumor necrosis factor-alpha blockers. , 2008, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[39]  P. V. van Helden,et al.  Differential cytokine secretion and early treatment response in patients with pulmonary tuberculosis , 2008, Clinical and experimental immunology.

[40]  R. Gie,et al.  Consensus statement on the revised World Health Organization recommendations for BCG vaccination in HIV-infected infants. , 2008, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[41]  A. Chiba,et al.  Innate Invariant NKT Cells Recognize Mycobacterium tuberculosis–Infected Macrophages, Produce Interferon-γ, and Kill Intracellular Bacteria , 2008, PLoS pathogens.

[42]  V. M. Frolov,et al.  Cytokine profiles of HIV patients with pulmonary tuberculosis resulting from adjunct immunotherapy with herbal phytoconcentrates Dzherelo and Anemin. , 2008, Cytokine.

[43]  M. Behr,et al.  NOD2-Deficient Mice Have Impaired Resistance to Mycobacterium tuberculosis Infection through Defective Innate and Adaptive Immunity1 , 2008, The Journal of Immunology.

[44]  X. Zhan,et al.  Phosphoantigen-activated V gamma 2V delta 2 T cells antagonize IL-2-induced CD4+CD25+Foxp3+ T regulatory cells in mycobacterial infection. , 2008, Blood.

[45]  M. Salmon,et al.  The kinetics of CD4+Foxp3+ T cell accumulation during a human cutaneous antigen-specific memory response in vivo. , 2008, The Journal of clinical investigation.

[46]  T. Ottenhoff,et al.  Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination. , 2008, Human immunology.

[47]  P. Crivelli,et al.  Clinical Usefulness of ELISPOT Assay on Pericardial Fluid in a Case of Suspected Tuberculous Pericarditis , 2008, Infection.

[48]  A. Krarup,et al.  Multiple routes of complement activation by Mycobacterium bovis BCG. , 2008, Molecular immunology.

[49]  P. Méndez-Samperio Role of antimicrobial peptides in host defense against mycobacterial infections , 2008, Peptides.

[50]  S. Kaufmann,et al.  Tuberculosis in Africa: learning from pathogenesis for biomarker identification. , 2008, Cell host & microbe.

[51]  R. Modlin,et al.  Human macrophage host defense against Mycobacterium tuberculosis. , 2008, Current opinion in immunology.

[52]  T. Ottenhoff,et al.  Human Anti-Inflammatory Macrophages Induce Foxp3+GITR+CD25+ Regulatory T Cells, Which Suppress via Membrane-Bound TGFβ-11 , 2008, The Journal of Immunology.

[53]  C. Leclerc,et al.  Effect of Attenuation of Treg during BCG Immunization on Anti-Mycobacterial Th1 Responses and Protection against Mycobacterium tuberculosis , 2008, PloS one.

[54]  A. Aseffa,et al.  Poor immunogenicity of BCG in helminth infected population is associated with increased in vitro TGF-beta production. , 2008, Vaccine.

[55]  D. Flower,et al.  In silico identified CCR4 antagonists target regulatory T cells and exert adjuvant activity in vaccination , 2008, Proceedings of the National Academy of Sciences.

[56]  K. Chu,et al.  Diagnosis of Central Nervous System Tuberculosis by T-Cell-Based Assays on Peripheral Blood and Cerebrospinal Fluid Mononuclear Cells , 2008, Clinical and Vaccine Immunology.

[57]  U. Schaible,et al.  Innate immunity in tuberculosis: myths and truth. , 2008, Microbes and infection.

[58]  P. V. van Helden,et al.  Differential Expression of Interleukin-4 (IL-4) and IL-4δ2 mRNA, but Not Transforming Growth Factor Beta (TGF-β), TGF-βRII, Foxp3, Gamma Interferon, T-bet, or GATA-3 mRNA, in Patients with Fast and Slow Responses to Antituberculosis Treatment , 2008, Clinical and Vaccine Immunology.

[59]  Chang‐you Wu,et al.  CD4+ CD25+ Treg cells inhibit human memory gammadelta T cells to produce IFN-gamma in response to M tuberculosis antigen ESAT-6. , 2008, Blood.

[60]  G. Kutsyna,et al.  Effect of oral immunomodulator Dzherelo in TB/HIV co-infected patients receiving anti-tuberculosis therapy under DOTS. , 2008, International immunopharmacology.

[61]  B. Marshall,et al.  Rapid diagnosis of Mycobacterium tuberculosis meningitis by enumeration of cerebrospinal fluid antigen-specific T-cells. , 2008, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[62]  R. Casetti,et al.  The Plasticity of γδ T Cells: Innate Immunity, Antigen Presentation and New Immunotherapy , 2008, Cellular and Molecular Immunology.

[63]  P. Hopewell,et al.  Tuberculosis and latent tuberculosis infection in close contacts of people with pulmonary tuberculosis in low-income and middle-income countries: a systematic review and meta-analysis. , 2008, The Lancet. Infectious diseases.

[64]  K. Higuchi,et al.  Interferon‐γ responses after isoniazid chemotherapy for latent tuberculosis , 2008, Respirology.

[65]  C. Bolliger,et al.  Evaluation of Adapted Whole-Blood Interferon-γ Release Assays for the Diagnosis of Pleural Tuberculosis , 2008, Respiration.

[66]  C. Senner,et al.  Cytological and Transcript Analyses Reveal Fat and Lazy Persister-Like Bacilli in Tuberculous Sputum , 2008, PLoS medicine.

[67]  M. Roederer,et al.  T-cell quality in memory and protection: implications for vaccine design , 2008, Nature Reviews Immunology.

[68]  N. Langeland,et al.  Evaluation of immune responses in HIV infected patients with pleural tuberculosis by the QuantiFERON® TB-Gold interferon-gamma assay , 2008, BMC infectious diseases.

[69]  N. Connell,et al.  Natural killer cells, glutathione, cytokines, and innate immunity against Mycobacterium tuberculosis. , 2008, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[70]  G. Kaplan,et al.  Bacillus Calmette-Guérin Vaccination of Human Newborns Induces T Cells with Complex Cytokine and Phenotypic Profiles1 , 2008, The Journal of Immunology.

[71]  Limin Zheng,et al.  Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria. , 2008, Microbes and infection.

[72]  G. Nicolardi,et al.  Abdominopelvic tuberculosis in gynaecology: Laparoscopical and new laboratory findings , 2008, The Australian & New Zealand journal of obstetrics & gynaecology.

[73]  Z. Toossi,et al.  Response to M. tuberculosis selected RD1 peptides in Ugandan HIV-infected patients with smear positive pulmonary tuberculosis: a pilot study , 2008, BMC infectious diseases.

[74]  M. Ernst,et al.  Rapid Diagnosis of CNS Tuberculosis by a T-Cell Interferon-γ Release Assay on Cerebrospinal Fluid Mononuclear Cells , 2008, Infection.

[75]  S. Kaufmann,et al.  Rational design of vaccines against tuberculosis directed by basic immunology. , 2008, International journal of medical microbiology : IJMM.

[76]  L. Fabbri,et al.  Use of a T-cell interferon-γ release assay for the diagnosis of tuberculous pleurisy , 2007, European Respiratory Journal.

[77]  C. Locht,et al.  Heparin-Binding-Hemagglutinin-Induced IFN-γ Release as a Diagnostic Tool for Latent Tuberculosis , 2007, PloS one.

[78]  T. Scriba,et al.  Immunological protection against tuberculosis. , 2007, South African medical journal = Suid-Afrikaanse tydskrif vir geneeskunde.

[79]  J. Keane,et al.  T helper 2 cytokines inhibit autophagic control of intracellular Mycobacterium tuberculosis. , 2007, Immunity.

[80]  A. Rudensky,et al.  Expansion and function of Foxp3-expressing T regulatory cells during tuberculosis , 2007, The Journal of experimental medicine.

[81]  F. Poccia,et al.  Central Memory Vγ9Vδ2 T Lymphocytes Primed and Expanded by Bacillus Calmette-Guérin-Infected Dendritic Cells Kill Mycobacterial-Infected Monocytes1 , 2007, The Journal of Immunology.

[82]  R. Modlin,et al.  Cutting Edge: Vitamin D-Mediated Human Antimicrobial Activity against Mycobacterium tuberculosis Is Dependent on the Induction of Cathelicidin1 , 2007, The Journal of Immunology.

[83]  G. Rook,et al.  Immunotherapeutics for tuberculosis in experimental animals: is there a common pathway activated by effective protocols? , 2007, The Journal of infectious diseases.

[84]  R. Wilkinson,et al.  Neutrophil-mediated innate immune resistance to mycobacteria. , 2007, The Journal of clinical investigation.

[85]  A. Aderem,et al.  A polymorphism in human TLR2 is associated with increased susceptibility to tuberculous meningitis , 2007, Genes and Immunity.

[86]  B. D. de Jong,et al.  Longitudinal Assessment of an ELISPOT Test for Mycobacterium tuberculosis Infection , 2007, PLoS medicine.

[87]  Armando Garsd,et al.  Safety and Activity of the Immune Modulator HE2000 on the Incidence of Tuberculosis and Other Opportunistic Infections in AIDS Patients , 2007, Antimicrobial Agents and Chemotherapy.

[88]  S. Alonso,et al.  Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy , 2007, Proceedings of the National Academy of Sciences.

[89]  R. Joshi,et al.  Sensitivity of a Whole-Blood Interferon-Gamma Assay Among Patients with Pulmonary Tuberculosis and Variations in T-Cell Responses During Anti-Tuberculosis Treatment , 2007, Infection.

[90]  P. Hopewell,et al.  Messenger RNA Expression of IL-8, FOXP3, and IL-12β Differentiates Latent Tuberculosis Infection from Disease1 , 2007, The Journal of Immunology.

[91]  S. Kaufmann,et al.  Cutting Edge: Regulatory T Cells Prevent Efficient Clearance of Mycobacterium tuberculosis , 2007, The Journal of Immunology.

[92]  A. Sher,et al.  Cooperation of Toll-like receptor signals in innate immune defence , 2007, Nature Reviews Immunology.

[93]  Z. Xing,et al.  Gamma Interferon Responses of CD4 and CD8 T-Cell Subsets Are Quantitatively Different and Independent of Each Other during Pulmonary Mycobacterium bovis BCG Infection , 2007, Infection and Immunity.

[94]  L. Cosmi,et al.  Detection by Flow Cytometry of ESAT-6- and PPD-Specific Circulating CD4+ T Lymphocytes as a Diagnostic Tool for Tuberculosis , 2006, International Archives of Allergy and Immunology.

[95]  Z. Toossi,et al.  Intestinal helminth co‐infection has a negative impact on both anti‐Mycobacterium tuberculosis immunity and clinical response to tuberculosis therapy , 2006, Clinical and experimental immunology.

[96]  Jennifer L. Martin,et al.  Surfactant Protein D Increases Fusion of Mycobacterium tuberculosis- Containing Phagosomes with Lysosomes in Human Macrophages , 2006, Infection and Immunity.

[97]  J. Deeks,et al.  Dynamic antigen-specific T-cell responses after point-source exposure to Mycobacterium tuberculosis. , 2006, American journal of respiratory and critical care medicine.

[98]  V. Deretic,et al.  Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria , 2006, Science.

[99]  L. Aarons,et al.  Optimal sampling strategies for early pharmacodynamic measures in tuberculosis. , 2006, The Journal of antimicrobial chemotherapy.

[100]  P. V. van Helden,et al.  Changes in leucocyte and lymphocyte subsets during tuberculosis treatment; prominence of CD3dimCD56+ natural killer T cells in fast treatment responders , 2006, Clinical and experimental immunology.

[101]  R. Adegbola,et al.  Early clinical trials with a new tuberculosis vaccine, MVA85A, in tuberculosis-endemic countries: issues in study design. , 2006, The Lancet. Infectious diseases.

[102]  R. Joshi,et al.  Serial testing of health care workers for tuberculosis using interferon-γ assay , 2006 .

[103]  S. Swain,et al.  Interleukin 12p40 is required for dendritic cell migration and T cell priming after Mycobacterium tuberculosis infection , 2006, The Journal of experimental medicine.

[104]  H. Weiner,et al.  Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells , 2006, Nature.

[105]  C. Locht,et al.  Heparin-binding hemagglutinin, from an extrapulmonary dissemination factor to a powerful diagnostic and protective antigen against tuberculosis. , 2006, Tuberculosis.

[106]  Alimuddin Zumla,et al.  Immune systems in developed and developing countries; implications for the design of vaccines that will work where BCG does not. , 2006, Tuberculosis.

[107]  S. Kalantri,et al.  New tools and emerging technologies for the diagnosis of tuberculosis: Part I. Latent tuberculosis , 2006, Expert review of molecular diagnostics.

[108]  J. Pieters Faculty Opinions recommendation of Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. , 2006 .

[109]  A. Lalvani,et al.  Regulatory T cells are expanded in blood and disease sites in patients with tuberculosis. , 2006, American journal of respiratory and critical care medicine.

[110]  Z. Toossi,et al.  A role for CD4+CD25+ T cells in regulation of the immune response during human tuberculosis , 2006, Clinical and experimental immunology.

[111]  R. Adegbola,et al.  Reversion of the ELISPOT test after treatment in Gambian tuberculosis cases , 2006, BMC infectious diseases.

[112]  J. Ellner,et al.  Mycobacterium tuberculosis growth control by lung macrophages and CD8 cells from patient contacts. , 2006, American journal of respiratory and critical care medicine.

[113]  B. Metchock,et al.  Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. , 2005, MMWR. Recommendations and reports : Morbidity and mortality weekly report. Recommendations and reports.

[114]  D. Machin,et al.  Early Clinical Trials , 2005 .

[115]  Jean-Louis Herrmann,et al.  DC-SIGN Induction in Alveolar Macrophages Defines Privileged Target Host Cells for Mycobacteria in Patients with Tuberculosis , 2005, PLoS medicine.

[116]  J. Deeks,et al.  Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study , 2005, The Lancet.

[117]  A. Azad,et al.  The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis , 2005, The Journal of experimental medicine.

[118]  Alimuddin Zumla,et al.  Lung remodeling in pulmonary tuberculosis. , 2005, The Journal of infectious diseases.

[119]  S. Jolles,et al.  Therapeutic Efficacy of High-Dose Intravenous Immunoglobulin in Mycobacterium tuberculosis Infection in Mice , 2005, Infection and Immunity.

[120]  S. Kaufmann,et al.  Increased vaccine efficacy against tuberculosis of recombinant Mycobacterium bovis bacille Calmette-Guérin mutants that secrete listeriolysin. , 2005, The Journal of clinical investigation.

[121]  Alimuddin Zumla,et al.  Immune responses to tuberculosis in developing countries: implications for new vaccines , 2005, Nature Reviews Immunology.

[122]  M. Horwitz,et al.  Enhancing the Protective Efficacy of Mycobacterium bovis BCG Vaccination against Tuberculosis by Boosting with the Mycobacterium tuberculosis Major Secretory Protein , 2005, Infection and Immunity.

[123]  P. Andersen,et al.  The success and failure of BCG — implications for a novel tuberculosis vaccine , 2005, Nature Reviews Microbiology.

[124]  A. Stryhn,et al.  Exchanging ESAT6 with TB10.4 in an Ag85B Fusion Molecule-Based Tuberculosis Subunit Vaccine: Efficient Protection and ESAT6-Based Sensitive Monitoring of Vaccine Efficacy 1 , 2005, The Journal of Immunology.

[125]  K. Dheda,et al.  Utility of the antigen-specific interferon-γ assay for the management of tuberculosis , 2005, Current opinion in pulmonary medicine.

[126]  Stefan H E Kaufmann,et al.  Annulling a dangerous liaison: vaccination strategies against AIDS and tuberculosis , 2005, Nature Medicine.

[127]  D. Lewinsohn,et al.  Role of CD8+ T lymphocytes in control of Mycobacterium tuberculosis infection. , 2005, Microbes and infection.

[128]  J. Ellner,et al.  Immunoadjuvant prednisolone therapy for HIV-associated tuberculosis: a phase 2 clinical trial in Uganda. , 2005, The Journal of infectious diseases.

[129]  Virginia Arcos,et al.  Immunotherapy with fragmented Mycobacterium tuberculosis cells increases the effectiveness of chemotherapy against a chronical infection in a murine model of tuberculosis. , 2005, Vaccine.

[130]  V. Deretic,et al.  Autophagy Is a Defense Mechanism Inhibiting BCG and Mycobacterium tuberculosis Survival in Infected Macrophages , 2004, Cell.

[131]  P. López-Saura,et al.  Adjuvant interferon gamma in patients with drug – resistant pulmonary tuberculosis: a pilot study , 2004, BMC infectious diseases.

[132]  M. Broder,et al.  Granulomatous infections due to tumor necrosis factor blockade: correction. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[133]  Z. Xing,et al.  Activation of CD8 T Cells by Mycobacterial Vaccination Protects against Pulmonary Tuberculosis in the Absence of CD4 T Cells1 , 2004, The Journal of Immunology.

[134]  K. Lee,et al.  Six-month Therapy with Aerosolized Interferon-γ for Refractory Multidrug-Resistant Pulmonary Tuberculosis , 2004, Journal of Korean medical science.

[135]  Matthijs Kramer,et al.  Human IL-23-producing type 1 macrophages promote but IL-10-producing type 2 macrophages subvert immunity to (myco)bacteria. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[136]  M. Amicosante,et al.  Use of a T cell-based assay for monitoring efficacy of antituberculosis therapy. , 2004, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[137]  V. Deretic,et al.  A tale of two lipids: Mycobacterium tuberculosis phagosome maturation arrest. , 2004, Current opinion in microbiology.

[138]  John L. Johnson,et al.  A study of the safety, immunology, virology, and microbiology of adjunctive etanercept in HIV-1-associated tuberculosis , 2004, AIDS.

[139]  D. Guwatudde,et al.  Tuberculosis in household contacts of infectious cases in Kampala, Uganda. , 2003, American journal of epidemiology.

[140]  Gregory A. Taylor,et al.  Immune Control of Tuberculosis by IFN-γ-Inducible LRG-47 , 2003, Science.

[141]  Shigeru Matsukura,et al.  Elevated levels of circulating adhesion molecules in patients with active pulmonary tuberculosis , 2003, Respirology.

[142]  S. Kaufmann,et al.  Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis , 2003, Nature Medicine.

[143]  John L. Johnson,et al.  Randomized trial of adjunctive interleukin-2 in adults with pulmonary tuberculosis. , 2003, American journal of respiratory and critical care medicine.

[144]  T. Geijtenbeek,et al.  Mycobacteria Target DC-SIGN to Suppress Dendritic Cell Function , 2003, The Journal of experimental medicine.

[145]  O. Schwartz,et al.  DC-SIGN Is the Major Mycobacterium tuberculosis Receptor on Human Dendritic Cells , 2003, The Journal of experimental medicine.

[146]  G. Dougan,et al.  Chronic bacterial infections: living with unwanted guests , 2002, Nature Immunology.

[147]  Alimuddin Zumla,et al.  Mycobacterium vaccae (SRL172) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis: a randomised placebo-controlled trial , 2002, The Lancet.

[148]  R. Dietze,et al.  Intestinal nematodes and pulmonary tuberculosis. , 2002, Revista da Sociedade Brasileira de Medicina Tropical.

[149]  G. Rook,et al.  Suppression of airway eosinophilia by killed Mycobacterium vaccae-induced allergen-specific regulatory T-cells , 2002, Nature Medicine.

[150]  Naresh J. Patel,et al.  Effect of an immunomodulator containing Mycobacterium w on sputum conversion in pulmonary tuberculosis. , 2002, Journal of the Indian Medical Association.

[151]  John Gatfield,et al.  Hijacking the host: survival of pathogenic mycobacteria inside macrophages. , 2002, Trends in microbiology.

[152]  G. Trinchieri Regulatory Role of T Cells Producing both Interferon γ and Interleukin 10 in Persistent Infection , 2001, The Journal of experimental medicine.

[153]  P. Sonnenberg,et al.  HIV-1 and recurrence, relapse, and reinfection of tuberculosis after cure: a cohort study in South African mineworkers , 2001, The Lancet.

[154]  J. Vekemans,et al.  Tuberculosis Contacts but Not Patients Have Higher Gamma Interferon Responses to ESAT-6 than Do Community Controls in The Gambia , 2001, Infection and Immunity.

[155]  S. Kaufmann,et al.  How can immunology contribute to the control of tuberculosis? , 2001, Nature Reviews Immunology.

[156]  John Chan,et al.  Tuberculosis: Latency and Reactivation , 2001, Infection and Immunity.

[157]  P. Fine,et al.  Environmental mycobacteria in northern Malawi: implications for the epidemiology of tuberculosis and leprosy , 2001, Epidemiology and Infection.

[158]  C. Immanuel,et al.  Serial evaluation of serum neopterin in HIV seronegative patients treated for tuberculosis. , 2001, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease.

[159]  B. Petros,et al.  Effect of deworming on human T cell responses to mycobacterial antigens in helminth‐exposed individuals before and after bacille Calmette–Guérin (BCG) vaccination , 2001, Clinical and experimental immunology.

[160]  P. Fine BCG: The Challenge Continues , 2001, Scandinavian journal of infectious diseases.

[161]  M. Horwitz,et al.  Recombinant bacillus calmette-guerin (BCG) vaccines expressing the Mycobacterium tuberculosis 30-kDa major secretory protein induce greater protective immunity against tuberculosis than conventional BCG vaccines in a highly susceptible animal model. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[162]  M. Bocchino,et al.  Mycobacterium tuberculosis and HIV co-infection in the lung: synergic immune dysregulation leading to disease progression. , 2000, Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace.

[163]  E. Arts,et al.  Greater Diversity of HIV‐1 Quasispecies in HIV‐Infected Individuals With Active Tuberculosis , 2000, Journal of acquired immune deficiency syndromes.

[164]  Z. Toossi,et al.  Pulmonary Mononuclear Cell Responses to Antigens of Mycobacterium tuberculosis in Healthy Household Contacts of Patients with Active Tuberculosis and Healthy Controls from the Community1 2 , 2000, The Journal of Immunology.

[165]  John L. Johnson,et al.  Randomized Controlled Trial of Mycobacterium vaccae Immunotherapy in Non-Human Immunodeficiency Virus-Infected Ugandan Adults with Newly Diagnosed Pulmonary Tuberculosis , 2000 .

[166]  Z. Toossi,et al.  Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy. , 1999, The Journal of infectious diseases.

[167]  M. Geletu,et al.  T-Cell Recognition of Mycobacterium tuberculosisCulture Filtrate Fractions in Tuberculosis Patients and Their Household Contacts , 1999, Infection and Immunity.

[168]  K. Moelling,et al.  Therapy of tuberculosis in mice by DNA vaccination , 1999, Nature.

[169]  Alimuddin Zumla,et al.  Immunotherapy with Mycobacterium vaccae in patients with newly diagnosed pulmonary tuberculosis: a randomised controlled trial , 1999, The Lancet.

[170]  J. Kazura,et al.  Helminth- and Bacillus Calmette-Guérin-induced immunity in children sensitized in utero to filariasis and schistosomiasis. , 1999, Journal of immunology.

[171]  G. Schoolnik,et al.  Comparative genomics of BCG vaccines by whole-genome DNA microarray. , 1999, Science.

[172]  S. Dorman,et al.  A human IFNGR1 small deletion hotspot associated with dominant susceptibility to mycobacterial infection , 1999, Nature Genetics.

[173]  M. Torres,et al.  Enhanced responses to Mycobacterium tuberculosis antigens by human alveolar lymphocytes during active pulmonary tuberculosis. , 1998, The Journal of infectious diseases.

[174]  J. Casanova,et al.  Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. , 1998, Science.

[175]  F. Deist,et al.  Impairment of mycobacterial immunity in human interleukin-12 receptor deficiency. , 1998, Science.

[176]  S. Kaufmann,et al.  Mycobacterium bovis Bacille Calmette-Guérin strains secreting listeriolysin of Listeria monocytogenes. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[177]  J. Ernst,et al.  Macrophage Receptors for Mycobacterium tuberculosis , 1998, Infection and Immunity.

[178]  A. Fischer,et al.  A causative relationship between mutant IFNgR1 alleles and impaired cellular response to IFNgamma in a compound heterozygous child. , 1998, American journal of human genetics.

[179]  M. Torres,et al.  Cytokine Profiles for Peripheral Blood Lymphocytes from Patients with Active Pulmonary Tuberculosis and Healthy Household Contacts in Response to the 30-Kilodalton Antigen ofMycobacterium tuberculosis , 1998, Infection and Immunity.

[180]  J. Mudgett,et al.  Identification of nitric oxide synthase as a protective locus against tuberculosis. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[181]  T. Kotsimbos,et al.  IFN-gamma and IL-12 are increased in active compared with inactive tuberculosis. , 1997, American journal of respiratory and critical care medicine.

[182]  M. Newport,et al.  A mutation in the interferon-gamma-receptor gene and susceptibility to mycobacterial infection. , 1996, The New England journal of medicine.

[183]  M. Torres,et al.  T lymphocytic and immature macrophage alveolitis in active pulmonary tuberculosis. , 1996, The Journal of infectious diseases.

[184]  Z. Toossi,et al.  Cross-modulation by transforming growth factor beta in human tuberculosis: suppression of antigen-driven blastogenesis and interferon gamma production. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[185]  H. Shiratsuchi,et al.  Selective induction of transforming growth factor beta in human monocytes by lipoarabinomannan of Mycobacterium tuberculosis , 1996, Infection and immunity.

[186]  W. Rom,et al.  Thalidomide Treatment Reduces Tumor Necrosis Factor α Production and Enhances Weight Gain in Patients with Pulmonary Tuberculosis , 1995, Molecular medicine.

[187]  D. Mitchell,et al.  Evidence for a Th1-like bronchoalveolar T-cell subset and predominance of interferon-gamma gene activation in pulmonary tuberculosis. , 1994, American journal of respiratory and critical care medicine.

[188]  J. Ellner,et al.  Complement receptor-mediated uptake and tumor necrosis factor-alpha-mediated growth inhibition of Mycobacterium tuberculosis by human alveolar macrophages. , 1994, Journal of immunology.

[189]  D. James Granulomatous Infections , 1993 .

[190]  D. Mitchison Assessment of new sterilizing drugs for treating pulmonary tuberculosis by culture at 2 months. , 1993, The American review of respiratory disease.

[191]  G. Schoolnik,et al.  An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms. , 1992, The New England journal of medicine.

[192]  M. Horwitz,et al.  Phagocytosis of Mycobacterium tuberculosis is mediated by human monocyte complement receptors and complement component C3. , 1990, Journal of immunology.

[193]  Eric N. Miller,et al.  HIV‐1 infection , 1990, Neurology.

[194]  A. Rattan,et al.  Prognostic value of 'C' reactive protein in tuberculosis. , 1989, Indian pediatrics.

[195]  S. Vermund,et al.  A prospective study of the risk of tuberculosis among intravenous drug users with human immunodeficiency virus infection. , 1989, The New England journal of medicine.

[196]  Comstock Gw Tuberculosis in twins: a re-analysis of the Prophit survey. , 1978, The American review of respiratory disease.

[197]  C. Valentine Bacillus Calmette Guérin. , 1947, American druggist.

[198]  Laurie J. Pencille,et al.  The Chest Pain Choice Decision Aid: A Randomized Trial , 2012, Circulation. Cardiovascular quality and outcomes.

[199]  A. Liston,et al.  Regulatory T Cells , 2011, Methods in Molecular Biology.

[200]  Alimuddin Zumla,et al.  Biomarkers for tuberculosis disease activity, cure, and relapse. , 2010, The Lancet. Infectious diseases.

[201]  A. Aseffa,et al.  Immunopathology and Infectious Diseases Compartmentalization of Immune Responses in Human Tuberculosis Few CD 8 Effector T Cells but Elevated Levels of FoxP 3 Regulatory T Cells in the Granulomatous Lesions , 2010 .

[202]  N. Sokolenko,et al.  Adjunct Immunotherapy of Tuberculosis in Drug-Resistant TB and TB / HIV Co-Infected Patients , 2009 .

[203]  E. Bateman,et al.  Within-Subject Variability and Boosting of T-Cell IFN-gamma Responses Following Tuberculin Skin Testing , 2009, ATS 2009.

[204]  J. Ellner,et al.  Compartmentalized bronchoalveolar IFN-gamma and IL-12 response in human pulmonary tuberculosis. , 2009, Tuberculosis.

[205]  E. Bateman,et al.  Rapid Imunodiagnosis of Site-Specific Tuberculosis: Is It Useful in Clinical Practice in South Africa? , 2009, ATS 2009.

[206]  P. Polgreen,et al.  Mycobacterial Disease Attributable to Tumor Necrosis Factor-α Blockers. Authors' reply , 2008 .

[207]  T. Kaisho,et al.  Direct extracellular interaction between the early secreted antigen ESAT-6 of Mycobacterium tuberculosis and TLR2 inhibits TLR signaling in macrophages , 2007, Nature Immunology.

[208]  Releve Epidemiologique Hebdomadaire Revised BCG vaccination guidelines for infants at risk for HIV infection. , 2007, Releve epidemiologique hebdomadaire.

[209]  Wang Li Adjuvant Effect of Mycobacterium Vaccae on Treatment of Recurrent Treated Pulmonary Tuberculosis:A Meta-analysis , 2007 .

[210]  F. Poccia,et al.  Central memory Vgamma9Vdelta2 T lymphocytes primed and expanded by bacillus Calmette-Guérin-infected dendritic cells kill mycobacterial-infected monocytes. , 2007, Journal of immunology.

[211]  藤井 俊策 子宮 natural killer 細胞の測定意義 , 2006 .

[212]  J. Dannenberg Pathogenesis of Human Pulmonary Tuberculosis: Insights from the Rabbit Model , 2006 .

[213]  R. Joshi,et al.  Serial testing of health care workers for tuberculosis using interferon-gamma assay. , 2006, American journal of respiratory and critical care medicine.

[214]  H. McShane,et al.  Boosting BCG with MVA85A: the first candidate subunit vaccine for tuberculosis in clinical trials. , 2005, Tuberculosis.

[215]  J. Mckinney,et al.  Immune control of tuberculosis by IFN-gamma-inducible LRG-47. , 2003, Science.

[216]  Alan D. Roberts,et al.  MURINE MODEL OF TUBERCULOSIS , 2002 .

[217]  J. Keane,et al.  Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. , 2001, The New England journal of medicine.

[218]  K. Chang,et al.  Imbalances between tumor necrosis factor-alpha and its soluble receptor forms, and interleukin-1beta and interleukin-1 receptor antagonist in BAL fluid of cavitary pulmonary tuberculosis. , 2000, Chest.

[219]  D. Hom,et al.  Randomized controlled trial of Mycobacterium vaccae immunotherapy in non-human immunodeficiency virus-infected ugandan adults with newly diagnosed pulmonary tuberculosis. The Uganda-Case Western Reserve University Research Collaboration. , 2000, The Journal of infectious diseases.

[220]  W. Goebel,et al.  Differential expression of , 1999 .

[221]  K. Fornataro,et al.  Immune control. , 1999, The Body positive.

[222]  A. Hill,et al.  Host genetic susceptibility to human tuberculosis. , 1998, Novartis Foundation symposium.

[223]  Lung Disease,et al.  Anti-tuberculosis drug resistance in the world : the WHO/IUATLD Global Project on Anti-tuberculosis Drug Resistance Surveillance , 1997 .

[224]  M. Firlik [Alveolar macrophages]. , 1985, Polski tygodnik lekarski.

[225]  O. Wasz‐Höckert,et al.  A bibliography of the complications of BCG vaccination. A comprehensive list of the world literature since the introduction of BCG up to July 1982, supplemented by over 100 personal communications. , 1984, Advances in tuberculosis research. Fortschritte der Tuberkuloseforschung. Progres de l'exploration de la tuberculose.

[226]  S. Grzybowski,et al.  Contacts of cases of active pulmonary tuberculosis. , 1975, Bulletin of the International Union against Tuberculosis.

[227]  A. I. Schastnyĭ [Selective induction]. , 1973, Zhurnal vysshei nervnoi deiatelnosti imeni I P Pavlova.

[228]  J. A. Myers BCG vaccination. , 1948, American review of tuberculosis.

[229]  Alimuddin Zumla,et al.  Mycobacterium vaccae ( SRL 172 ) immunotherapy as an adjunct to standard antituberculosis treatment in HIV-infected adults with pulmonary tuberculosis : a randomised placebo-controlled trial , 2022 .