scholarly journals Clinical and Diagnostic Developments of a Gamma Interferon Release Assay for Use in Bovine Tuberculosis Control Programs

2013 ◽  
Vol 20 (12) ◽  
pp. 1827-1835 ◽  
Author(s):  
K. E. Bass ◽  
B. J. Nonnecke ◽  
M. V. Palmer ◽  
T. C. Thacker ◽  
R. Hardegger ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Second Generation ◽  
Gamma Interferon ◽  
Tuberculosis Control ◽  
Content Type ◽  
Control Programs ◽  
Release Assay ◽  
Ifn Γ ◽  
First And Second Generation ◽  
And Control

ABSTRACTCurrently, the Bovigam assay is used as an official supplemental test within bovine tuberculosis control programs. The objectives of the present study were to evaluate twoMycobacterium bovis-specific peptide cocktails and purified protein derivatives (PPDs) from two sources, liquid and lyophilized antigen preparations. PPDs and peptide cocktails were also used for comparison of a second-generation gamma interferon (IFN-γ) release assay kit with the currently licensed first-generation kit (Bovigam; Prionics AG). Three strains ofM. boviswere used for experimental challenge:M. bovis95-1315,M. bovisRavenel, andM. bovis10-7428. Additionally, samples from a tuberculosis-affected herd (i.e., naturally infected) were evaluated. Robust responses to both peptide cocktails, HP (PC-HP) and ESAT-6/CFP10 (PC-EC), and the PPDs were elicited as early as 3 weeks after challenge. Only minor differences in responses to Commonwealth Serum Laboratories (CSL) and Lelystad PPDs were detected with samples from experimentally infected animals. For instance, responses to LelystadM. avium-derived PPD (PPDa) exceeded the respective responses to the CSL PPDa inM. bovisRavenel-infected and control animals. However, a 1:4 dilution of stimulated plasma demonstrated greater separation of PPDb from PPDa responses (i.e., PPDb minus PPDa) with the use of Lelystad PPDs, suggesting that Lelystad PPDs provide greater diagnostic sensitivity than CSL PPDs. The responses to lyophilized and liquid antigen preparations did not differ. Responses detected with first- and second-generation IFN-γ release assay kits (Bovigam) did not differ throughout the study. In conclusion, antigens may be stored in a lyophilized state without loss in potency, PC-HP and PC-EC are dependable biomarkers for aiding in the detection of bovine tuberculosis, and second-generation Bovigam kits are comparable to currently used kits.

scholarly journals Key Role of Effector Memory CD4+T Lymphocytes in a Short-Incubation Heparin-Binding Hemagglutinin Gamma Interferon Release Assay for the Detection of Latent Tuberculosis

2014 ◽  
Vol 21 (3) ◽  
pp. 321-328 ◽  
Author(s):  
Chloé Wyndham-Thomas ◽  
Véronique Corbière ◽  
Violette Dirix ◽  
Kaatje Smits ◽  
Fanny Domont ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Latent Tuberculosis ◽  
Gamma Interferon ◽  
Effector Memory ◽  
The Novel ◽  
Infection Status ◽  
Heparin Binding ◽  
Content Type ◽  
Release Assay ◽  
Ifn Γ

ABSTRACTThe treatment of latent tuberculosis infection (LTBI) in target populations is one of the current WHO strategies for preventing active tuberculosis (TB) infection and reducing theMycobacterium tuberculosisreservoir. Therefore, powerful LTBI screening tools are indispensable. A gamma interferon release assay (IGRA) in response to the stimulation of peripheral blood mononuclear cells by the latency antigen native heparin-binding hemagglutinin (nHBHA-IGRA) has proven its potential for this purpose. We have evaluated its possible optimization through a reduction of incubation time from 96 to 24 h, while compensating for this by adding interleukin 7 (IL-7) to the medium. We have also investigated the phenotypes of the gamma interferon (IFN-γ)-producing cells after both short and long incubation times. One hundred thirty-one nonimmunocompromised patients were recruited from 3 Brussels-based university hospitals. They were divided into 1 of 4 subgroups according to theirM. tuberculosisinfection status (LTBI, TB infection, undeterminedM. tuberculosisinfection status, and noninfected controls). The novel 24-h nHBHA-IGRA was performed for all subjects, and a simultaneous 96-h classical HBHA-IGRA was performed for 79 individuals. The results showed a good correlation between the two tests, and the novel 24-h nHBHA-IGRA maintained the principal advantages of the classical test, namely, a high specificity for LTBI diagnosis, an absence of interference ofMycobacterium bovisBCG vaccination during infancy, and a relative discrimination between LTBI and TB infection. Whereas the commercialized IGRAs show a greater sensitivity for recent than for remoteM. tuberculosisinfections, the 24-h nHBHA-IGRA appears to have comparable diagnostic powers for recent and remote LTBI. The IFN-γ detected by the 24-h nHBHA-IGRA was mainly secreted by effector memory CD4+T lymphocytes, a finding suggestive of continuous HBHA presentation during latency.

scholarly journals Assessment of a Protein Cocktail-Based Skin Test for Bovine Tuberculosis in a Double-Blind Field Test in Cattle

2013 ◽  
Vol 20 (4) ◽  
pp. 482-490 ◽  
Author(s):  
Ting Xin ◽  
Hong Jia ◽  
Jiabo Ding ◽  
Pingjun Li ◽  
Hongjun Yang ◽  
...  
Keyword(s):  
Tuberculin Skin Test ◽  
Skin Test ◽  
Bovine Tuberculosis ◽  
Relative Sensitivity ◽  
Skin Thickness ◽  
Double Blind ◽  
Content Type ◽  
Relative Specificity ◽  
Release Assay ◽  
Ifn Γ

ABSTRACTBovine tuberculosis (bTB) is a worldwide zoonosis caused mainly byMycobacterium bovis.The traditional diagnostic method used often is the tuberculin skin test, which uses bovine purified protein derivatives (PPD-B). However, it is difficult to maintain uniformity of PPD-B from batch to batch, and it shares common antigens with nonpathogenic environmental mycobacteria. To overcome these problems,M. bovis-specific antigens that showed good T cell stimulation, such as CFP-10, ESAT-6, Rv3615c, etc., have been used in the skin test, but there have been no large-scale clinical studies on these antigens. In this study, two combinations (CFP-10/ESAT-6/TB10.4 protein cocktail and CFP-10/ESAT-6/Rv3872/MPT63 protein cocktail) were developed and used as stimuli in the skin test. Cattle were double-blind tested to assess the efficiency of the protein cocktail-based skin tests. The results showed that the CFP-10/ESAT-6/TB10.4 protein cocktail-based skin test can differentiate TB-infected cattle fromMycobacterium avium-infected ones and that it shows a high degree of agreement with the traditional tuberculin skin test (κ = 0.8536) and gamma interferon (IFN-γ) release assay (κ = 0.8154). Compared to the tuberculin skin test, the relative sensitivity and relative specificity of the CFP-10/ESAT-6/TB10.4-based skin test were 87% and 97%, respectively., The relative sensitivity and relative specificity of the CFP-10/ESAT-6/TB10.4-based skin test were 93% and 92%, respectively, on comparison with the IFN-γ release assay. The correlation between the increases in skin thickness observed after the inoculation of stimuli was high (PPD-B versus CFP-10/ESAT-6/TB10.4, Spearmanrof 0.8435). The correlation between the optical density at 450 nm (OD450) obtained after blood stimulation with PPD-B and the increase in skin thickness observed after inoculation of the CFP-10/ESAT-6/TB10.4 protein cocktail was high (Spearmanr= 0.7335). Therefore, the CFP-10/ESAT-6/TB10.4-based skin test responses correlate to traditional measures of bovine TB evaluation, including skin test and gamma interferon release assay.

scholarly journals Immediate Interferon Gamma Induction Determines Murine Host Compatibility Differences between Toxoplasma gondii and Neospora caninum

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Rachel S. Coombs ◽  
Matthew L. Blank ◽  
Elizabeth D. English ◽  
Yaw Adomako-Ankomah ◽  
Ifeanyi-Chukwu Samuel Urama ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Interferon Gamma ◽  
Neospora Caninum ◽  
Ectopic Expression ◽  
Parasite Burden ◽  
Interleukin 12 ◽  
Content Type ◽  
Ifn Γ ◽  
And Control

ABSTRACT Rodents are critical for the transmission of Toxoplasma gondii to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. Neospora caninum is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to N. caninum and T. gondii and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). N. caninum-infected mice produced significantly higher levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) by as early as 4 hpi, but the level of IFN-γ was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. “Immediate” IFN-γ and IL-12p40 production was not detected in MyD88−/− mice. However, unlike IL-12p40−/− and IFN-γ−/− mice, MyD88−/− mice survived N. caninum infections at the dose used in this study. Serial measures of parasite burden showed that MyD88−/− mice were more susceptible to N. caninum infections than wild-type (WT) mice, and control of parasite burdens correlated with a pulse of serum IFN-γ at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-γ was partially dependent on the T. gondii mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of N. caninum profilin in T. gondii had no impact on early IFN-γ production or parasite proliferation. Our data indicate that T. gondii is capable of evading host detection during the first hours after infection, while N. caninum is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.

scholarly journals Assessment of the specificity of a gamma-interferon test performed with specific antigens to detect bovine tuberculosis, after non-negative results to intradermal tuberculin testing

2019 ◽  
Vol 6 (1) ◽  
pp. e000335 ◽  
Author(s):  
Anne Praud ◽  
Clémence Bourély ◽  
Maria-Laura Boschiroli ◽  
Barbara Dufour
Keyword(s):  
Bovine Tuberculosis ◽  
Gamma Interferon ◽  
Skin Tests ◽  
Negative Results ◽  
In Series ◽  
Specific Antigens ◽  
Ifn Γ ◽  
Tuberculin Testing ◽  
Cattle Herds ◽  
Higher Sensitivity

In cattle herds in France, cervical skin tests (STs) using simple intradermal tuberculin (SIT) are performed to detect bovine tuberculosis (bTB). When positive results are found on ST screening, the herd is considered to be ‘under suspicion’ and confined, raising economic issues. The suspicion can be lifted by carrying out a single intradermal cervical comparative test (SICCT) at least six weeks later.The authors conducted an experimental study in France between 2013 and 2015 to assess the accuracy of the gamma-interferon test (IFN-γ), used in series after a non-negative result to ST screening, and to study the possibility of replacing the SICCT performed six weeks later by an IFN performed within a few days. Data were collected concerning 40 infected and 1825 bTB-free animals from herds with non-negative results to ST screening. This study showed that the IFN-γ test based on specific antigens and performed within a few days of a non-negative result to the ST has higher sensitivity than the SICCT performed six weeks later and equal specificity. The IFN test is more convenient to perform; however, it is more expensive. The IFN-γ test based on MIX antigens may be a useful alternative to the SICCT, to shorten the confinement period of suspect herds without underdetecting bTB.

scholarly journals Gamma Interferon Is Required for Chlamydia Clearance but Is Dispensable for T Cell Homing to the Genital Tract

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Jennifer D. Helble ◽  
Rodrigo J. Gonzalez ◽  
Ulrich H. von Andrian ◽  
Michael N. Starnbach
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Chlamydia Trachomatis ◽  
Genital Tract ◽  
Gamma Interferon ◽  
Cell Homing ◽  
Content Type ◽  
T Cell Homing ◽  
Ifn Γ

ABSTRACT While there is no effective vaccine against Chlamydia trachomatis infection, previous work has demonstrated the importance of C. trachomatis-specific CD4+ T cells (NR1 T cells) in pathogen clearance. Specifically, NR1 T cells have been shown to be protective in mice, and this protection depends on the host’s ability to sense the cytokine gamma interferon (IFN-γ). However, it is unclear what role NR1 production or sensing of IFN-γ plays in T cell homing to the genital tract or T cell-mediated protection against C. trachomatis. Using two-photon microscopy and flow cytometry, we found that naive wild-type (WT), IFN-γ−/−, and IFN-γR−/− NR1 T cells specifically home to sections in the genital tract that contain C. trachomatis. We also determined that protection against infection requires production of IFN-γ from either NR1 T cells or endogenous cells, further highlighting the importance of IFN-γ in clearing C. trachomatis infection. IMPORTANCE Chlamydia trachomatis is an important mucosal pathogen that is the leading cause of sexually transmitted bacterial infections in the United States. Despite this, there is no vaccine currently available. In order to develop such a vaccine, it is necessary to understand the components of the immune response that can lead to protection against this pathogen. It is well known that antigen-specific CD4+ T cells are critical for Chlamydia clearance, but the contexts in which they are protective or not protective are unknown. Here, we aimed to characterize the importance of gamma interferon production and sensing by T cells and the effects on the immune response to C. trachomatis. Our work here helps to define the contexts in which antigen-specific T cells can be protective, which is critical to our ability to design an effective and protective vaccine against C. trachomatis.

scholarly journals GABARAPL2 Is Critical for Growth Restriction of Toxoplasma gondii in HeLa Cells Treated with Gamma Interferon

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Zhaoxia Zhang ◽  
Haorong Gu ◽  
Qi Li ◽  
Jun Zheng ◽  
Shinuo Cao ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Hela Cells ◽  
Critical Role ◽  
Gamma Interferon ◽  
Growth Restriction ◽  
Membrane Structures ◽  
Content Type ◽  
Receptor Associated Protein ◽  
Ifn Γ ◽  
And Function

ABSTRACT Gamma interferon (IFN-γ)-induced innate immune responses play important roles in the inhibition of Toxoplasma gondii infection. It has been reported that IFN-γ stimulates non-acidification-dependent growth restriction of T. gondii in HeLa cells, but the mechanism remains unclear. Here, we found that γ-aminobutyric acid (GABA) receptor-associated protein-like 2 (GABARAPL2) plays a critical role in parasite restriction in IFN-γ-treated HeLa cells. GABARAPL2 is recruited to membrane structures surrounding parasitophorous vacuoles (PV). Autophagy adaptors are required for the proper localization and function of GABARAPL2 in the IFN-γ -induced immune response. These findings provide further understanding of a noncanonical autophagy pathway responsible for IFN-γ-dependent inhibition of T. gondii growth in human HeLa cells and demonstrate the critical role of GABARAPL2 in this response.

scholarly journals An Early Intestinal Mucosal Source of Gamma Interferon Is Associated with Resistance to and Control of Cryptosporidium parvum Infection in Mice

2005 ◽  
Vol 73 (12) ◽  
pp. 8425-8428 ◽  
Author(s):  
Brett A. Leav ◽  
Masaru Yoshida ◽  
Kathleen Rogers ◽  
Seth Cohen ◽  
Nihal Godiwala ◽  
...  
Keyword(s):  
Cryptosporidium Parvum ◽  
Neutralizing Antibody ◽  
Cell Receptor ◽  
Intraepithelial Lymphocytes ◽  
Gamma Interferon ◽  
Susceptibility To Infection ◽  
Ifn Γ ◽  
Rapid Kinetics ◽  
And Control ◽  
Kinetics Of

ABSTRACT Resistance to and control of Cryptosporidium parvum infection in mice in the absence of adaptive immunity appears to be gamma interferon (IFN-γ) dependent. Using an IFN-γ-neutralizing antibody in a murine model, we demonstrated increased susceptibility to infection within 24 h. We correlated this early resistance and control with increased mucosal expression of IFN-γ and demonstrate that CD8+ T-cell receptor αβ intestinal intraepithelial lymphocytes express and secrete this cytokine shortly after infection. The rapid kinetics of IFN-γ expression and secretion by naive CD8+ T cells in response to a protozoan pathogen have not previously been demonstrated.

Immigrant and second-generation Turkish entrepreneurs in Melbourne Australia

2015 ◽  
Vol 21 (2) ◽  
pp. 154-174 ◽  
Author(s):  
Yasemin Soydas ◽  
Torgeir Aleti
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Government Support ◽  
Entrepreneurial Activity ◽  
Content Type ◽  
Positive Effects ◽  
Immigrant Entrepreneurs ◽  
Generation Immigrant ◽  
Business Establishment ◽  
First And Second Generation

Purpose – The purpose of this paper is to examine the key differences between first- and second-generation immigrant entrepreneurs in their path to entrepreneurship. The aim of the study is to better understand entrepreneurial motivations amongst immigrants by comparing first- and second-generation entrepreneurs in their motivation for business entry, reliance on co-ethnic market, use of social and financial capital, business planning and marketing practices. Design/methodology/approach – Using an interpretivist approach and a qualitative design, this study comprises 20 in-depth interviews with first- and second-generation Turkish entrepreneurs (TEs) in Melbourne, Australia. Turks in Australia were chosen because of their high level of entrepreneurial activity. In order to uncover deep-seeded motivations, participants were interviewed in a face-to-face format guided by a semi-structured interview guide. Findings – The second-generation TEs were distinctively different from their first-generation counterparts in motivation for business entry, business establishment and use of ethnicity. The analysis shows that although the generations differ in their approach to business establishment, they both appear to be drawn to entrepreneurship based on “pull factors”. This is in contrast with previous literature suggesting that first-generation immigrant entrepreneurs were motivated by “push factors”. Originality/value – This paper suggests that both first- and second-generation immigrant entrepreneurs are “pulled” into entrepreneurship voluntarily. While the first-generation entrepreneurs seem to be motivated/pulled by financial reasons, the second generation are motivated by opportunity recognition, status and ambition. Nevertheless, a lack of trust in government support agency is found within both generations. Thus, outreach activities towards entrepreneurial immigrant communities may have positive effects for the economy as well as in the integration of ethnic enclaves.

scholarly journals Distinct Response Kinetics of Gamma Interferon and Interleukin-4 in Bovine Tuberculosis

2000 ◽  
Vol 68 (9) ◽  
pp. 5393-5400 ◽  
Author(s):  
S. G. Rhodes ◽  
N. Palmer ◽  
S. P. Graham ◽  
A. E. Bianco ◽  
R. G. Hewinson ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Gamma Interferon ◽  
Interleukin 4 ◽  
Early Increase ◽  
Onchocerca Ochengi ◽  
Ifn Γ ◽  
Bovine Tuberculin ◽  
Kinetics Of ◽  
Experimental Challenge

ABSTRACT This study shows that gamma interferon (IFN-γ) and interleukin-4 (IL-4) cytokine responses are produced by peripheral blood cells in cattle infected with Mycobacterium bovis. The different kinetics of the IFN-γ and IL-4 responses to bovine tuberculin and to ESAT-6 following experimental intratracheal infection with M. bovis are described. An early increase in IFN-γ was observed that was maintained throughout the period studied. In contrast, the IL-4 response was delayed and confined to a peak of activity lasting 6 to 8 weeks. Interestingly, an experimental challenge of cattle with a lower dose of M. bovis which did not result in the development of lesions, positive DTH skin test, or substantial IFN-γ responses nevertheless generated strong specific IL-4 responses. Investigation of naturally infected M. bovis field reactors showed increased IFN-γ and IL-4 responses compared to uninfected cattle and that both of these cytokines were equally able to differentiate infected from uninfected animals. The magnitude of theM. bovis-induced IL-4 responses were found to be similar to the antigen-specific IL-4 responses of cattle infected with the parasitic nematode Onchocerca ochengi, further supporting the presence of this type 2 cytokine in bovine tuberculosis.

scholarly journals Cattle Husbandry in Ethiopia Is a Predominant Factor Affecting the Pathology of Bovine Tuberculosis and Gamma Interferon Responses to Mycobacterial Antigens

2006 ◽  
Vol 13 (9) ◽  
pp. 1030-1036 ◽  
Author(s):  
Gobena Ameni ◽  
Abraham Aseffa ◽  
Howard Engers ◽  
Douglas Young ◽  
Glyn Hewinson ◽  
...  
Keyword(s):  
Bovine Tuberculosis ◽  
Control Program ◽  
Economic Problem ◽  
Gamma Interferon ◽  
Dominant Factor ◽  
Zebu Cattle ◽  
Holstein Cattle ◽  
Ifn Γ ◽  
Mycobacterial Antigens ◽  
Cattle Husbandry

ABSTRACT Bovine tuberculosis is a major economic problem and a potential public health risk. Improved diagnostics like the gamma interferon (IFN-γ) test with ESAT6 and/or CFP10 could contribute to the control program. We assessed IFN-γ responses in zebu (Ethiopian Arsi breed) and Holstein cattle kept indoors or in a pasture to tuberculin purified protein derivative (PPD) and an ESAT6-CFP10 protein cocktail. Furthermore, the intensity and distribution of pathology of bovine tuberculosis were compared between the two breeds. Our data demonstrated significantly (all P < 0.02) higher IFN-γ responses to avian PPD, bovine PPD, and the ESAT6-CFP10 protein cocktail in Holstein than in zebu cattle, while lesion severities in infected animals and tuberculin skin test responses did not differ significantly (P > 0.05) between the two breeds. Holstein cattle that were kept indoors produced significantly (all P < 0.01) higher IFN-γ levels in response to avian PPD, bovine PPD, and the ESAT6-CFP10 protein cocktail than did Holstein cattle kept in a pasture. Moreover, lesion severity was significantly higher in Holstein cattle kept indoors (P = 0.001) than in those kept in the pasture. Lesions were localized predominantly in the digestive tract in cattle kept in a pasture, while they were localized in the respiratory tract in cattle kept indoors. In conclusion, in Holstein cattle, husbandry was a dominant factor influencing the severity of tuberculosis lesions and IFN-γ responses to mycobacterial antigens compared to breed. A difference in the cellular immune response between zebu and Holstein cattle was observed, while tuberculosis lesion severities were identical in the two breeds, when both were kept in a pasture.

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