A Summary of the Third Global Interferon-γ Release Assay Symposium

2013 ◽  
Vol 34 (6) ◽  
pp. 619-624 ◽  
Author(s):  
Antonino Catanzaro ◽  
Charles Daley
Keyword(s):  
Immune Response ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Tests ◽  
The Third ◽  
Specific Antigens ◽  
Ifn Γ

Studies over the past several decades have dramatically increased our understanding of the immune response to Mycobacterium tuberculosis infection, and advances in proteomics and genomics have led to a new class of immune-diagnostic tests, termed interferon-γ (IFN-γ) release assays (IGRAs), which appear to obviate many of the problems encountered with the tuberculin skin test (TST). Worldwide, 2 IGRAs are currently commercially available. QuantiFERON-TB Gold In-Tube (Cellestis) is a third-generation product that uses an enzyme-linked immunosorbent assay to measure IFN-γ generated in whole blood stimulated with M. tuberculosis–specific antigens. T-Spot-TB (Oxford Immunotec) employs enzyme-linked immunosorbent spot technology to enumerate the number of purified lymphocytes that respond to M. tuberculosis–specific antigens by producing IFN-γ. These in vitro tests measure the host immune response to M. tuberculosis–specific antigens, which virtually eliminates false-positive cross reactions caused by bacillus Calmette-Guérin vaccination and/or exposure to environmental nontuberculous mycobacteria that plague the interpretation and accuracy of the tuberculin skin test (TST). The high specificity of IGRAs, together with sensitivity commensurate with or better than that of the TST, promises an accurate diagnosis and the ability to focus tuberculosis-control activities on those who are actually infected with M. tuberculosis. The Third Global Symposium was held over a 3-day period and was presented by the University of California, San Diego, Continuing Medical Education department; slides and sound recordings of each presentation are available at http://cme.ucsd.edu/igras/syllabus.html. A moderated discussion is also available at http://cme.ucsd.edu/igrasvideo. This document provides a summary of the key findings of the meeting, specifically focusing on the use of IGRAs in screening healthcare worker populations.

scholarly journals Effect ofTityus serrulatusvenom on cytokine production and the activity of murine macrophages

2002 ◽  
Vol 11 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Vera L. Petricevich
Keyword(s):  
Cytokine Production ◽  
Peritoneal Macrophages ◽  
Interferon Γ ◽  
Enzyme Linked Immunosorbent Assay ◽  
No Production ◽  
Dependent Manner ◽  
Immune Functions ◽  
Macrophage Activity ◽  
Ifn Γ

The purpose of this study was to investigate the effects ofTityus serrulatusvenom (TSV) on murine peritoneal macrophages evaluated in terms of activation. The effects of crude TSV were analysed by detection of cytokines, oxygen intermediate metabolites (H2O2) and nitric oxide (NO) in supernatants of peritoneal macrophages. Several functional bioassays were employed including anin vitromodel for envenomating: cytotoxicity of TSV was assessed using the lyses percentage. Tumor necrosis factor (TNF) activity was assayed by measuring its cytotoxic activity on L-929 cells, and interleukin-6 (IL-6) and interferon-γ (IFN-γ) were assayed by enzyme-linked immunosorbent assay, whereas NO levels were detected by Griess colorimetric reactions in culture supernatant of macrophages incubated with TSV and subsequently exposed to either lipopolysaccharide or IFN-γ. Incubation of macrophages with TSV increased production of IL-6 and IFN-γ in a dose-dependent manner. TNF production was not detected in supernatants treated with TSV at any concentration. The increase in IL-6 secretion was not associated with concentration-dependent cytoxicity of TSV on these cells. These data suggest that the cytotoxicity does not appear to be the main cause of an increased cytokine production by these cells. Although NO is an important effector molecule in macrophage microbicidal activity, the inducing potential of the test compounds for its release was found to be very moderate, ranging from 125 to 800 mM. Interestingly, NO levels of peritoneal macrophages were increased after IFN-γ. Moreover, NO production had an apparent effect on macrophage activity. The results obtained here also shown that the TSV induces an important elevation in H2O2release. These results combined with NO production suggest that TSV possesses significant immunomodulatory activities capable of stimulating immune functionsin vitro.

scholarly journals Reciprocal Protective Immunity againstBordetella pertussis and Bordetella parapertussis in a Murine Model of Respiratory Infection

2001 ◽  
Vol 69 (11) ◽  
pp. 6981-6986 ◽  
Author(s):  
Mineo Watanabe ◽  
Masaaki Nagai
Keyword(s):  
Immune Response ◽  
Respiratory Infection ◽  
Murine Model ◽  
Protective Immunity ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Spleen Cells ◽  
Bordetella Parapertussis ◽  
Ifn Γ

ABSTRACT The protective immunity induced by infection with Bordetella pertussis and with Bordetella parapertussis was examined in a murine model of respiratory infection. Convalescent mice that had been infected by aerosol with B. pertussis or with B. parapertussis exhibited a protective immune response against B. pertussis and also against B. parapertussis. Anti-filamentous hemagglutinin (anti-FHA) serum immunoglobulin G (IgG) and anti-FHA lung IgA antibodies were detected in both mice infected with B. pertussis and those infected with B. parapertussis. Antibodies against pertussis toxin (anti-PT) and against killed B. pertussis cells were detected in mice infected with B. pertussis. Pertactin-specific antibodies and antibodies against killed B. parapertussis cells were detected in mice infected with B. parapertussis. Spleen cells from mice infected with B. pertussis secreted interferon-γ (IFN-γ) in response to stimulation by FHA or PT. Spleen cells from mice infected with B. parapertussis also secreted IFN-γ in response to FHA. Interleukin-4 was not produced in response to any of the antigens tested. The profiles of cytokine secretion in vitro revealed induction of a Th1-biased immune response during convalescence from infection by B. pertussis and byB. parapertussis. It is possible that Th1 and Th2 responses against FHA might be related to the reciprocal protection achieved in our murine model.

Rate of Latent Tuberculosis Infection Detected by Occupational Health Screening of Nurses New to a London Teaching Hospital

2009 ◽  
Vol 30 (6) ◽  
pp. 581-584 ◽  
Author(s):  
Priya Khanna ◽  
Vladyslav Nikolayevskyy ◽  
Fiona Warburton ◽  
Elek Dobson ◽  
Francis Drobniewski
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Interferon Γ ◽  
Tuberculosis Infection ◽  
Release Assay ◽  
Ifn Γ ◽  
Positive Results ◽  
Tuberculosis Prevalence

The prevalence of latent tuberculosis infection in a cohort of nurses new to a London hospital was 7.6% (13 of 171), using an interferon-γ(IFN-γ) release assay, and 16.2% (24 of 148), using the tuberculin skin test. On multivariate analysis, birth in a country with tuberculosis prevalence of more than 40 cases per 100,000 population was associated with positive results of both the IFN-γ release assay and the tuberculin skin test.

scholarly journals MyD88 Primes Macrophages for Full-Scale Activation by Interferon-γ yet Mediates Few Responses to Mycobacterium tuberculosis

2003 ◽  
Vol 198 (7) ◽  
pp. 987-997 ◽  
Author(s):  
Shuangping Shi ◽  
Carl Nathan ◽  
Dirk Schnappinger ◽  
Jörg Drenkow ◽  
Michele Fuortes ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Large Scale ◽  
Nuclear Factor Κb ◽  
Interferon Γ ◽  
Full Scale ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ifn Γ ◽  
Microbial Products ◽  
Oxide Synthase

Macrophages are activated from a resting state by a combination of cytokines and microbial products. Microbes are often sensed through Toll-like receptors signaling through MyD88. We used large-scale microarrays in multiple replicate experiments followed by stringent statistical analysis to compare gene expression in wild-type (WT) and MyD88−/− macrophages. We confirmed key results by quantitative reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Surprisingly, many genes, such as inducible nitric oxide synthase, IRG-1, IP-10, MIG, RANTES, and interleukin 6 were induced by interferon (IFN)-γ from 5- to 100-fold less extensively in MyD88−/− macrophages than in WT macrophages. Thus, widespread, full-scale activation of macrophages by IFN-γ requires MyD88. Analysis of the mechanism revealed that MyD88 mediates a process of self-priming by which resting macrophages produce a low level of tumor necrosis factor. This and other factors lead to basal activation of nuclear factor κB, which synergizes with IFN-γ for gene induction. In contrast, infection by live, virulent Mycobacterium tuberculosis (Mtb) activated macrophages largely through MyD88-independent pathways, and macrophages did not need MyD88 to kill Mtb in vitro. Thus, MyD88 plays a dynamic role in resting macrophages that supports IFN-γ–dependent activation, whereas macrophages can respond to a complex microbial stimulus, the tubercle bacillus, chiefly by other routes.

scholarly journals Cellular immune response of Curraleiro Pé-duro and Nellore calves following Mycobacterium bovis-BCG vaccination

2013 ◽  
Vol 33 (12) ◽  
pp. 1403-1408
Author(s):  
Mayara Fernanda Maggioli ◽  
Joyce Rodrigues Lobo ◽  
Maria Clorinda Soares Fioravanti ◽  
André Kipnis ◽  
Ana Paula Junqueira-Kipnis
Keyword(s):  
Immune Response ◽  
Tuberculin Skin Test ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Blood Levels ◽  
Cd4 Cells ◽  
Test Reaction ◽  
Positive Role ◽  
Bcg Vaccination ◽  
Ifn Γ

The present study aimed to assess the CD4, CD8 and γδ blood levels for Curraleiro Pé-duro, as well as the specific IFN-γ response after BCG vaccination using flow cytometry. The specific immune response against BCG was also evaluated by tuberculin skin test, performed before and 45 days after the vaccination. For comparison purposes, the same parameters were investigated on Nellore calves, an exotic bovine with resistance previously demonstrated. Naturally, Curraleiro Pé-duro animals had greater levels of CD4, CD8 and γδ lymphocytes (p<0.05). In response to vaccine, Curraleiro Pé-duro showed greater ability to respond specifically to BCG, generating resistance profile (Th1), evidenced by greater number of antigen specific CD4+ cells producing IFN-γ (p<0.05) and also higher tuberculin skin test reaction (p<0.05). Additionally, vaccinated Curraleiro Pé-duro calves had higher CD4 cells numbers than both Nellore control (p<0.05) and vaccinated groups (p<0.05). Curraleiro Pé-duro calves' higher basal lymphocytes blood level and stronger response in both IFN-γ and tuberculin skin test parameters probably play a positive role on protection/resistance to Mycobacterium bovis.

scholarly journals Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test

2010 ◽  
Vol 37 (5) ◽  
pp. 1166-1174 ◽  
Author(s):  
N. Altet-Gomez ◽  
M. De Souza-Galvao ◽  
I. Latorre ◽  
C. Mila ◽  
M. A. Jimenez ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
In Vitro Tests

scholarly journals Association of Tuberculin-Boosted Antibody Responses with Pathology and Cell-Mediated Immunity in Cattle Vaccinated with Mycobacterium bovis BCG and Infected with M. bovis

2004 ◽  
Vol 72 (5) ◽  
pp. 2462-2467 ◽  
Author(s):  
Konstantin Lyashchenko ◽  
Adam O. Whelan ◽  
Rena Greenwald ◽  
John M. Pollock ◽  
Peter Andersen ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Mycobacterium Bovis ◽  
Vaccine Development ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cell Mediated Immunity ◽  
Humoral Immune ◽  
Humoral Immune Responses

ABSTRACT Vaccine development and our understanding of the pathology of bovine tuberculosis in cattle would be greatly facilitated by definition of the immunological correlates of protection and/or pathology. In this study we analyzed humoral immune responses in Mycobacterium bovis BCG-vaccinated and control cattle (in particular, the relationship between the intradermal comparative tuberculin skin test and serum immunoglobulin G [IgG] responses) against a range of mycobacterial antigens (MPB59, MPB64, MPB70, MPB83, ESAT-6, CFP-10, Acr1, and PstS-1) by multiantigen print immunoassay and conventional enzyme-linked immunosorbent assay. Following M. bovis infection, the comparative tuberculin skin test strongly boosted IgG, IgG1, and IgG2 antibody responses, particularly against MPB83 and MPB70, in unvaccinated cattle but failed to boost these responses, or did so only weakly, in BCG-vaccinated calves. In addition, the skin test-induced increases in MPB83-specific IgG responses correlated positively with bacterial loads and ESAT-6-induced in vitro gamma interferon responses. In conclusion, both the negative correlation of skin test-enhanced MPB83-specific antibody responses with BCG-induced protection and their positive correlation with bacterial loads can serve as useful markers for vaccine efficacy after challenge.

Tests for tuberculosis infection: landscape analysis

2021 ◽  
pp. 2100167
Author(s):  
Yohhei Hamada ◽  
Daniela Maria Cirillo ◽  
Alberto Matteelli ◽  
Adam Penn-Nicholson ◽  
Molebogeng X. Rangaka ◽  
...  
Keyword(s):  
Scale Up ◽  
Predictive Performance ◽  
Interferon Γ ◽  
World Health ◽  
Skin Tests ◽  
Enzyme Linked Immunosorbent Assay ◽  
In Vitro Tests ◽  
Published Data ◽  
Operational Characteristics

Only tuberculin skin tests (TST) and two interferon-γ release assays (IGRA) – QuantiFERON-TB Gold In-Tube and T-SPOT.TB – are currently endorsed by the World Health Organization as tests for tuberculosis (TB) infection. While IGRAs are more specific than TST, they require sophisticated laboratory infrastructure and are costly to perform. However, both types of tests have limited performance to predict development of active TB. Tests with improved predictive performance and operational characteristics are needed.We reviewed the current landscape of tests for TB infection identified through a web-based survey targeting diagnostic manufacturers globally.We identified 20 tests for TB infection including 15 in-vitro tests and five skin tests. Thirteen of the in-vitro tests are whole-blood IGRA and 14 uses early secreted antigenic target 6 (ESAT-6) and culture filtrate protein 10 (CFP-10), with or without additional antigens. Ten are based on assays other than an enzyme-linked immunosorbent assay such as a fluorescent lateral flow assay, which requires less manual operation and shorter assay time and hence is more suitable for decentralisation compared to the existing IGRA.Four of the five skin tests use ESAT-6 and CFP-10 proteins while the remaining one uses a new antigen that is specific to Mycobacterium tuberculosis complex.New tests have the potential to improve accuracy, operational characteristics and end-user access to tests for TB infection. However, published data in various populations and settings are limited for most new tests. Evaluation of these new tests in a standardised design would facilitate their endorsement and programmatic scale-up.

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