scholarly journals Age associated level of estradiol (E2) and progesterone (4) influence IL-8 response to Mycobacterium tuberculosis (Mtb) antigens in women.

2020 ◽  
Author(s):  
Priscillia Virginie Liesse MBOUROU MENSAH ◽  
Marielle LEBOUENY ◽  
Paulin NDONG ESSONE ◽  
Anicet Christel MALOUPAZOA SIAWAYA ◽  
Amel Kévin ALAME-EMANE ◽  
...  

Abstract Tuberculosis (TB) is an intracellular infection controlled the effective recruitment of effectors immune cells at infection site. In aged premenopausal or menopausal women, there is an increased pro-inflammatory cytokines secretion suggesting an underlying link between cytokines response and estrogen (E2) and progesterone (P4) levels. In this study we compared women aged 40 years old and above (premenopausal) and women aged below 40 years old with and without latent TB infection to determine the link between E2, P4 and cytokines response to Mycobacterium tuberculosis (M. tuberculosis) stimuli. E2 and P4 levels were significantly higher in women under 40 years old than in women above 40 years old irrespective their LTB status (p < [0.0001–0.05]). In women under 40 years old, E2 and P4 were found to correlate negatively and significantly with IL-8 response to M. tuberculosis antigens stimulation ((p < [0.001–0.01]). Furthermore, M. tuberculosis IL-8 specific response was significantly higher in women above 40 years old than women under 40 years old. This study demonstrates that women aging and the linked hormonal changes are associated with hence IL-8 response to M. tuberculosis antigen, which may have implications for the age-related susceptibility or resistance to active tuberculosis.

2015 ◽  
Vol 4 (3) ◽  
pp. 69-74
Author(s):  
Ling Zhou

AbstractMost people with latentMycobacterium tuberculosisinfection can partly develop active tuberculosis (TB). Therefore, diagnosis of this condition bears significance in early TB prevention. To date, the main methods for diagnosis of latent TB infection (LTBI) include tuberculin skin test and interferon γ release test. These two methods feature their own advantages and disadvantages. Although new diagnostic markers continually emerge, no uniform diagnostic criteria are available for TB detection. This study summarizes several methods for diagnosis of LTBI and new related markers and their application value in clinical practice.


2021 ◽  
Vol 11 ◽  
Author(s):  
Qing-yuan Yang ◽  
Yu-tong Zhang ◽  
Jia-ni Xiao ◽  
Yu-shuo Liang ◽  
Ping Ji ◽  
...  

Long-term immunoreactivity to mycobacterial antigens in Bovis Calmette-Guérin (BCG)-vaccinated population is not well investigated. Herein, 361 volunteer healthy donors (HDs) with neonatal BCG vaccination from Shanghai region (China) were enrolled. They were subdivided into ESAT-6/CFP10- (E6C10-) and ESAT-6/CFP10+ (E6C10+) groups based on gamma-interferon release assays (IGRAs). Three mycobacterial antigens, including Rv0934, Rv3006, and Rv3841, were subjected to the determination of immunoreactivity by ELISPOT assay. The immunoreactivities to three mycobacterial antigens were firstly compared among TB patients (N=39), E6C10+ HDs (N=78, 21.61% of HDs) and E6C10- HDs (N=283, 78.39% of HDs). It was revealed that Rv3006 was dominant upon M.tb infection, while Rv3841 was likely to be more responsive upon latent TB infection. In E6C10- population, the immunoreactivity to Rv3841 maintained along with aging, whereas those to Rv3006 and Rv0934 attenuated in E6C10- HDs older than 45 years old. Our study implies the shift of dominant antigens at different infection statuses, providing the clues for the selection of mycobacterial antigens in vaccine development and precision revaccination in the future.


2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A31.2-A31
Author(s):  
Awa Gindeh ◽  
Simon Donkor ◽  
Olumuyiwa Owolabi

BackgroundTuberculosis (TB) is still a major global health problem with about one-quarter of the global population infected with the causative pathogen, Mycobacterium tuberculosis (Mtb). The role of T-cells in the adaptive immune response against Mtb has been extensively studied with little information on the role of B-cells. B-cells produce antibodies and differentiate into plasma and memory B-cells. Plasmablasts are a subset of plasma cells only present in the peripheral circulation following an ongoing infection or vaccination. Immunoglobulin G’(IgG) especially IgG2 mounts more efficient immune response against bacterial infections, mainly attributed to the high affinity of IgG2 binding to the Fcγ receptor. Therefore, we hypothesised that Mtb-specific IgG +plasmablasts may be a useful biomarker of TB infection status.MethodsEx-vivo B-cell enzyme-linked immunospot (ELISPOT) was used to identify plasmablasts responses to Mtb-specific antigens ESAT-6/CFP-10 (EC), together with non-specific Mtb purified protein derivative (PPD) and a positive (total IgG) and negative (media only) control from adults with active TB pre- and post-treatment (n=20) or with latent TB infection (LTBI; n=20) in The Gambia.ResultsFrequencies of Mtb-specific plasmablasts were significantly higher in active TB cases pre-treatment compared to post-treatment (p<0.0001) and LTBI with no difference seen following PPD stimulation. Interestingly, total IgG +cells were lower in the cases at recruitment but increased following treatment indicating the relative proportion of Mtb-specific responses were also significantly different (p=0.034) prior to therapy.ConclusionThese data show that B-cell responses are differentially modulated during active and latent TB infection, suggesting that plasmablasts may be a useful biomarker for TB infection in TB-endemic settings.


2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
So-Yi Chang ◽  
Mei-Ling Chen ◽  
Meng-Rui Lee ◽  
Yun-Chieh Liang ◽  
Tzu-Pin Lu ◽  
...  

One-fourth of the human population is estimated to have been exposed to Mycobacterium tuberculosis (Mtb) and carries the infection in its latent form. This latent infection presents a lifelong risk of developing active tuberculosis (TB) disease, and persons with latent TB infection (LTBI) are significant contributors to the pool of active TB cases. Genetic polymorphisms among hosts have been shown to contribute to the outcome of Mtb infection. The SP110 gene, which encodes an interferon-induced nuclear protein, has been shown to control host innate immunity to Mtb infection. In this study, we provide experimental data demonstrating the ability of the gene to control genetic susceptibility to latent and active TB infection. Genetic variants of the SP110 gene were investigated in the Taiwanese population (including 301 pulmonary TB patients, 68 LTBI individuals, and 278 healthy household contacts of the TB patients), and their association with susceptibility to latent and active TB infection was examined by performing an association analysis in a case-control study. We identified several SNPs (rs7580900, rs7580912, rs9061, rs11556887, and rs2241525) in the SP110 gene that are associated with susceptibility to LTBI and/or TB disease. Our studies further showed that the same SNPs may have opposite effects on the control of susceptibility to LTBI versus TB. In addition, our analyses demonstrated that the SP110 rs9061 SNP was associated with tumor necrosis factor-α (TNFα) levels in plasma in LTBI subjects. The results suggest that the polymorphisms within SP110 have a role in controlling genetic susceptibility to latent and active TB infection in humans. To the best of our knowledge, this is the first report showing that the SP110 variants are associated with susceptibility to LTBI. Our study also demonstrated that the identified SP110 SNPs displayed the potential to predict the risk of LTBI and subsequent TB progression in Taiwan.


Author(s):  
Salim Can ◽  
Ayse Sahin ◽  
Nazan Dalgic ◽  
Deniz Aygün

Abstract Objective This study aimed to investigate interferon-gamma-inducible protein-10 (IP-10) values in serum and urine in pediatric patients in the diagnosis of active tuberculosis (TB) or latent TB infection (LTBI). It also aimed to investigate whether it can be used as a biomarker to distinguish between active TB and LTBI. Methods Our study comprised active TB (25 patients), LTBI (25 patients), and the “infected” group (50 patients) formed by combining the two groups. As the control group, 37 healthy children were included in the study. TB skin test, plasma IP-10, and urine IP-10 measurements were performed in all patients included in the study. An additional QuantiFERON-TB Gold In-Tube (QFT-GIT) test was performed on patients evaluated as active TB or LTBI. Results Plasma IP-10 levels of the patients in the active TB, LTBI, and the “infected” groups were significantly higher than the control group (p = 0.022, p = 0.028, and p = 0.007, respectively). Urine IP-10 was successful in distinguishing the active TB and “infected” groups from the control group (p = 0.007 and p = 0.047, respectively). Also, in the combined use of the tests, when QFT-GIT and urine IP-10 were positive together, active TB and LTBI could be distinguished (p = 0.044). Urine IP-10 levels were found to be significantly higher in those with pulmonary TB than those with extrapulmonary TB (p = 0.012). Conclusion Our findings suggest that IP-10 can be used as a useful biomarker in the diagnosis of active TB in children.


2010 ◽  
Vol 17 (12) ◽  
pp. 1985-1990 ◽  
Author(s):  
Shu Zhang ◽  
Lingyun Shao ◽  
Ling Mo ◽  
Jiazhen Chen ◽  
Feifei Wang ◽  
...  

ABSTRACT T-cell-based gamma interferon (IFN-γ) release assays (IGRAs) using Mycobacterium tuberculosis-specific antigens have shown higher sensitivity and specificity than the routine tuberculin skin test (TST). However, the effects of Mycobacterium bovis BCG vaccination and anti-tuberculosis (TB) treatment on dynamic T-cell responses to M. tuberculosis-specific antigens in active TB cases have rarely been investigated in regions where TB is endemic. Eighty-nine patients with active pulmonary TB (ATB) and 57 healthy controls (HC) from China were recruited and tested by sputum smear and culture, TSTs, and IGRAs with M. tuberculosis-specific antigens ESAT-6 and CFP-10 (T-SPOT.TB) as well as purified protein derivative (PPD) stimulation. All 146 participants were screened by the T-SPOT.TB assay at recruitment. T-SPOT.TB-positive rates in ATB and HC groups were 87.6% (78/89) and 21.1% (12/57), respectively. Of 38 ATB patients who were both TST and T-SPOT.TB tested, the positive rates were 73.7% (28/38) and 94.7% (36/38), respectively (P = 0.0215), and those in the HC group were 62.3% (33/53) and 18.9% (10/53), respectively (P < 0.0001). The T-SPOT.TB-positive rates declined during TB treatment and were 94.4% (51/54), 86.4% (19/22), and 61.5% (8/13) for ATB patients receiving 0- to 1-month, 1- to 3-month, and 3- to 6-month anti-TB treatment, respectively. The IGRA is a most promising test for both active TB and latent TB infection (LTBI) diagnosis due to the improvement of its specificity and convenience, especially in the Mycobacterium bovis BCG-vaccinated population. Furthermore, the T-SPOT.TB assay using ESAT-6 and CFP-10 in ATB patients during anti-TB treatment could serve as a potential predictor of therapeutic efficacy.


PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207787 ◽  
Author(s):  
Philip Raj Abraham ◽  
Kamakshi Prudhula Devalraju ◽  
Vishwanath Jha ◽  
Vijaya Lakshmi Valluri ◽  
Sangita Mukhopadhyay

2020 ◽  
Vol 58 (6) ◽  
Author(s):  
Danilo Buonsenso ◽  
Giovanni Delogu ◽  
Clelia Perricone ◽  
Roberta Grossi ◽  
Angela Careddu ◽  
...  

ABSTRACT Compared to its predecessor QuantiFERON-TB Gold In Tube (QFT-IT), QuantiFERON-TB Gold Plus (QFT-Plus) contains an additional antigen tube (TB2), stimulating both CD4+ and CD8+ T cells. The ability to discriminate CD4+ and CD8+ responses is suggested to be useful in differentiating stages of Mycobacterium tuberculosis infection. While QFT-Plus has already been evaluated in adults, there are not enough data in children evaluated for suspected active tuberculosis (TB) or latent TB infection (LTBI). A prospective cross-sectional study was conducted among children aged 0 to 17 years who were evaluated for suspected active TB or screened for LTBI. All children underwent QFT-Plus and further clinical, radiological, and/or microbiological analyses according to clinical scenario. Of the 198 children enrolled, 43 (21.7%) were tested because of suspicion of active TB. A total of 12/43 (27.9%) were diagnosed with active TB, and among these, 10/12 (83.3%) had a positive QFT-Plus assay. Of the 155 children screened for LTBI, 18 (11.6%) had a positive QFT-Plus, and 5 (2.5%) had an indeterminate result. TB1 and TB2 quantitative responses were not able to discriminate active disease from latent infection. The percent agreement between TB1 and TB2 was 100%. QFT-Plus assay showed good sensitivity for active TB and was particularly useful for the evaluation of children with suspected LTBI, giving a low rate of indeterminate results in this group. More studies are needed to properly evaluate QFT-Plus ability in discriminating active disease from latent infection.


mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Evelyn Guirado ◽  
Uchenna Mbawuike ◽  
Tracy L. Keiser ◽  
Jesus Arcos ◽  
Abul K. Azad ◽  
...  

ABSTRACTGranulomas sit at the center of tuberculosis (TB) immunopathogenesis. Progress in biomarkers and treatment specific to the human granuloma environment is hindered by the lack of a relevant and tractable infection model that better accounts for the complexity of the host immune response as well as pathogen counterresponses that subvert host immunity in granulomas. Here we developed and characterized anin vitrogranuloma model derived from human peripheral blood mononuclear cells (PBMCs) and autologous serum. Importantly, we interrogated this model for its ability to discriminate between host and bacterial determinants in individuals with and without latent TB infection (LTBI). By the use of this model, we provide the first evidence that granuloma formation, bacterial survival, lymphocyte proliferation, pro- and anti-inflammatory cytokines, and lipid body accumulation are significantly altered in LTBI individuals. Moreover, we show a specific transcriptional signature ofMycobacterium tuberculosisassociated with survival within human granuloma structures depending on the host immune status. Our report provides fundamentally new information on how the human host immune status and bacterial transcriptional signature may dictate early granuloma formation and outcome and provides evidence for the validity of the granuloma model and its potential applications.IMPORTANCEIn 2012, approximately 1.3 million people died from tuberculosis (TB), the highest rate for any single bacterial pathogen. The long-term control of TB requires a better understanding ofMycobacterium tuberculosispathogenesis in appropriate research models. Granulomas represent the characteristic host tissue response to TB, controlling the bacilli while concentrating the immune response to a limited area. However, complete eradication of bacteria does not occur, sinceM. tuberculosishas its own strategies to adapt and persist. Thus, theM. tuberculosis-containing granuloma represents a unique environment for dictating both the host immune response and the bacterial response. Here we developed and characterized anin vitrogranuloma model derived from blood cells of individuals with latent TB infection that more accurately defines the human immune response and metabolic profiles ofM. tuberculosiswithin this uniquely regulated immune environment. This model may also prove beneficial for understanding other granulomatous diseases.


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