Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

Stringari, Lorenzzo Lyrio; Covre, Luciana Polaco; Silva, Flávia Dias Coelho da; Oliveira, Victor De; Campana, Maria Carolina; Hadad, David Jamil; Palaci, Moisés; Salgame, Padmini; Dietze, Reynaldo; Gomes, Daniel; Ribeiro‐Rodrigues, Rodrigo

doi:10.1371/journal.pntd.0009605

Cited by 12 publications

(7 citation statements)

References 45 publications

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“…However, the Tregs estimations in this study were controversial. Previous small-scale studies ( Semple et al, 2013 ; Stringari et al, 2021 ) suggested an increasing trend of peripheral blood Tregs counts in active TB cases compared to the numbers in latent cases. Due to the methodological limitations of the studies, the abundance of Tregs mainly represented cell activity but not necessarily the exact count.…”

Section: Discussionmentioning

confidence: 90%

Identification and validation of a T-cell-related MIR600HG/hsa-mir-21-5p competing endogenous RNA network in tuberculosis activation based on integrated bioinformatics approaches

Guan²,

Peng³

et al. 2022

Front. Genet.

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Background: T cells play critical roles in the progression of tuberculosis (TB); however, knowledge regarding these molecular mechanisms remains inadequate. This study constructed a critical ceRNA network was constructed to identify the potentially important role of TB activation via T-cell regulation.Methods: We performed integrated bioinformatics analysis in a randomly selected training set from the GSE37250 dataset. After estimating the abundance of 18 types of T cells using ImmuCellAI, critical T-cell subsets were determined by their diagnostic accuracy in distinguishing active from latent TB. We then identified the critical genes associated with T-cell subsets in TB activation through co-expression analysis and PPI network prediction. Then, the ceRNA network was constructed based on RNA complementarity detection on the DIANA-LncBase and mirDIP platform. The gene biomarkers included in the ceRNA network were lncRNA, miRNA, and targeting mRNA. We then applied an elastic net regression model to develop a diagnostic classifier to assess the significance of the gene biomarkers in clinical applications. Internal and external validations were performed to assess the repeatability and generalizability.Results: We identified CD4+ T, Tr1, nTreg, iTreg, and Tfh as T cells critical for TB activation. A ceRNA network mediated by the MIR600HG/hsa-mir-21-5p axis was constructed, in which the significant gene cluster regulated the critical T subsets in TB activation. MIR600HG, hsa-mir-21-5p, and five targeting mRNAs (BCL11B, ETS1, EPHA4, KLF12, and KMT2A) were identified as gene biomarkers. The elastic net diagnostic classifier accurately distinguished active TB from latent. The validation analysis confirmed that our findings had high generalizability in different host background cases.Conclusion: The findings of this study provided novel insight into the underlying mechanisms of TB activation and identifying prospective biomarkers for clinical applications.

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Section: Discussionmentioning

confidence: 90%

Identification and validation of a T-cell-related MIR600HG/hsa-mir-21-5p competing endogenous RNA network in tuberculosis activation based on integrated bioinformatics approaches

Guan²,

Peng³

et al. 2022

Front. Genet.

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“…These cell types were chosen because they are hallmarks of effector and regulatory T cells populations respectively. These are the two major populations present in allergic and tolerance reactions [60, 61], along with memory B cells [62, 63].…”

Section: Discussionmentioning

confidence: 99%

Expansion of Antigen- Specific Memory Cells as a Potential Booster for Food Tolerance Induction

Silva¹,

Marmello²,

Bentes³

et al. 2023

Preprint

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Approximately 3% of children in Western countries are diagnosed with peanut allergy, a likely lifelong disease. The preferred treatment for food allergy is allergen avoidance. However, oral immunotherapy is an FDA-approved treatment to re-induce tolerance, still, not all patients respond as expected. Thus, the aim of this work is to evaluate whether the association of an antigen-specific tolerogenic (oral tolerance) bystander effect can ameliorate the recovery of inflamed intestinal mucosa. Adult male C57BL/6 mice were divided into five groups, four of which were submitted to an intestinal inflammation induction protocol to peanuts. After sensitization, experimental groups were orally challenged with either peanuts or a hybrid diet (peanuts + mouse chow). In a second stage, groups were sensitized, challenged with peanuts, and then received either peanuts, hybrid diet, or ovalbumin chow during the recovery period of the inflamed mucosa. Results showed no changes in diet intake and body weight. Polyisotypic anti-peanut IgG and IgG1 were significantly increased in the serum from animals in allergic groups. The group that received the hybrid diet showed an increase in CD4+CD25+Foxp3+ regulatory T cells, as well as in B220+CD3-CD27+ memory B cells. Histology of the duodenum showed a decrease in intraepithelial leukocytes in animals who received hybrid diet. Together, our results show that when the tolerogen is added to a diet containing the allergen, it can ameliorate the induction of local inflammation. Simultaneously offering the allergen with a tolerated food increased the mucosal recovery due to the expansion of previously induced memory cells.

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“…Regulatory T cells (suppressor T cells/Tregs) are a type of T cell that can suppress the immune system, significantly inhibiting the proliferation of CD4+ and CD8+ (Th1) by producing antiinflammatory cytokines such as IL-10. Stringari et al 30 study in PBMC cells with active TB patients showed an increase in the population of Tregs cells compared to PBMC cells in healthy people.…”

Section: Dicky Santosa Et Al: Effect Of Esat-6 On Phagocytosis Activi...mentioning

confidence: 93%

Effect of ESAT-6 on Phagocytosis Activity, ROS, NO, IFN-γ, and IL-10 in Peripheral Blood Mononuclear Cells of Pulmonary Tuberculosis Patients

Santosa

Gurnida

Sastramihardja

et al. 2022

Glob Med Health Commun

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Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB) that lives intracellularly. MTB can inhibit lysosomal enzymes and phagolysosomal fusion, which is challenging to eliminate. These are due to ESAT-6/CFP-10 originating from the RD1 region genome that expresses the Esx-1 type VII secretion system. Esx-1 encodes Esx-A (ESAT-6) and Esx-B (CFP-10), potential vaccine candidates still under research and development. ESAT-6/CFP-10 is predicted to affect macrophage phagocytic activity, IFN-γ, ROS/NO, and IL-10 levels. Several studies have begun to focus on the ESAT-6 antigen due to the high levels of ESAT-6 antibody found in pleural effusion and granuloma fluid. They can last up to 1 year compared to CFP-10 in experimental animals. This study aimed to analyze the effect of ESAT-6 on the phagocytic activity of macrophages, ROS/NO, IFN-γ, and IL-10 in peripheral blood mononuclear cells (PBMCs) cultures of pulmonary TB patients. It is experimental laboratory research with a post-test-only control group design with PBMCs from October 2019 to December 2020 in the Aretha Laboratory Bandung. There were two groups: the negative group (without ESAT-6) and the positive group (with ESAT-6). Six subjects were sampled at the Pindad Hospital in Bandung, and the research was carried out at the Aretha Laboratory in Bandung. Statistical analysis using paired t test. There was a significant difference between the negative and positive groups (p<0.05). ESAT-6 can decrease macrophage phagocytic activity, intracellular ROS/NO, and IFN-γ but increase IL-10 levels.

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Increase of CD4+CD25highFoxP3+ cells impairs in vitro human microbicidal activity against Mycobacterium tuberculosis during latent and acute pulmonary tuberculosis

Cited by 12 publications

References 45 publications

Identification and validation of a T-cell-related MIR600HG/hsa-mir-21-5p competing endogenous RNA network in tuberculosis activation based on integrated bioinformatics approaches

Identification and validation of a T-cell-related MIR600HG/hsa-mir-21-5p competing endogenous RNA network in tuberculosis activation based on integrated bioinformatics approaches

Expansion of Antigen- Specific Memory Cells as a Potential Booster for Food Tolerance Induction

Effect of ESAT-6 on Phagocytosis Activity, ROS, NO, IFN-γ, and IL-10 in Peripheral Blood Mononuclear Cells of Pulmonary Tuberculosis Patients

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