scholarly journals Immune Response to Mycobacterial Infection: Lessons from Flow Cytometry

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Nikoletta Rovina ◽  
Marios Panagiotou ◽  
Konstantinos Pontikis ◽  
Magdalini Kyriakopoulou ◽  
Nikolaos G. Koulouris ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Latent Tuberculosis ◽  
Mycobacterial Infection ◽  
Diagnostic Tools ◽  
Diagnostic Biomarkers ◽  
Reliable Diagnosis ◽  
Latent Tb ◽  
Two Stages

Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response againstMycobacterium tuberculosis(Mtb) at certain stages of infection as revealed by flow cytometry to date.

scholarly journals The Role of microRNAs and Long Non-Coding RNAs in the Regulation of the Immune Response to Mycobacterium tuberculosis Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Manikuntala Kundu ◽  
Joyoti Basu
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Signaling Pathways ◽  
Defense Mechanisms ◽  
Latent Tuberculosis ◽  
Mycobacterial Infection ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Non Coding Rnas

Non-coding RNAs have emerged as critical regulators of the immune response to infection. MicroRNAs (miRNAs) are small non-coding RNAs which regulate host defense mechanisms against viruses, bacteria and fungi. They are involved in the delicate interplay between Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), and its host, which dictates the course of infection. Differential expression of miRNAs upon infection with M. tuberculosis, regulates host signaling pathways linked to inflammation, autophagy, apoptosis and polarization of macrophages. Experimental evidence suggests that virulent M. tuberculosis often utilize host miRNAs to promote pathogenicity by restricting host-mediated antibacterial signaling pathways. At the same time, host- induced miRNAs augment antibacterial processes such as autophagy, to limit bacterial proliferation. Targeting miRNAs is an emerging option for host-directed therapies. Recent studies have explored the role of long non-coding RNA (lncRNAs) in the regulation of the host response to mycobacterial infection. Among other functions, lncRNAs interact with chromatin remodelers to regulate gene expression and also function as miRNA sponges. In this review we attempt to summarize recent literature on how miRNAs and lncRNAs are differentially expressed during the course of M. tuberculosis infection, and how they influence the outcome of infection. We also discuss the potential use of non-coding RNAs as biomarkers of active and latent tuberculosis. Comprehensive understanding of the role of these non-coding RNAs is the first step towards developing RNA-based therapeutics and diagnostic tools for the treatment of TB.

scholarly journals Cytokine Biosignature of Active and Latent Mycobacterium Tuberculosis Infection in Children

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 517
Author(s):  
Magdalena Druszczynska ◽  
Michal Seweryn ◽  
Sebastian Wawrocki ◽  
Magdalena Kowalewska-Pietrzak ◽  
Anna Pankowska ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Inflammatory Mediators ◽  
Latent Tuberculosis ◽  
Serum Levels ◽  
Diagnostic Tools ◽  
Mycobacterium Tuberculosis Infection ◽  
Only Children ◽  
Latent Tb ◽  
Ifn Γ ◽  
Multiplex Bead

None of the currently used diagnostic tools are efficient enough in diagnosing Mycobacterium tuberculosis (M.tb) infection in children. The study was aimed to identify cytokine biosignatures characterizing active and latent tuberculosis (TB) in children. Using a multiplex bead-based technology, we analyzed the levels of 53 Th17-related cytokines and inflammatory mediators in sera from 216 BCG-vaccinated children diagnosed with active TB (TB) or latent TB (LTBI) as well as uninfected controls (HC). Children with active TB, compared to HC children, showed reduced serum levels of IL-17A, MMP-2, OPN, PTX-3, and markedly elevated concentrations of APRIL/TNFSF13. IL-21, sCD40L, MMP-2, and IL-8 were significantly differentially expressed in the comparisons between groups: (1) HC versus TB and LTBI (jointly), and (2) TB versus LTBI. The panel consisting of APRIL/TNFSF13, sCD30/TNFRSF8, IFN-α2, IFN-γ, IL-2, sIL-6Rα, IL-8, IL-11, IL-29/IFN-λ1, LIGHT/TNFSF14, MMP-1, MMP-2, MMP-3, osteocalcin, osteopontin, TSLP, and TWEAK/TNFSF12 possessed a discriminatory potential for the differentiation between TB and LTBI children. Serum-based host biosignatures carry the potential to aid the diagnosis of childhood M.tb infections. The proposed panels of markers allow distinguishing not only children infected with M.tb from uninfected individuals but also children with active TB from those with latent TB.

scholarly journals PO 8383 THE ROLE OF PLASMA B CELLS IN MYCOBACTERIUM TUBERCULOSIS INFECTION AND DISEASE

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A31.2-A31
Author(s):  
Awa Gindeh ◽  
Simon Donkor ◽  
Olumuyiwa Owolabi
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
B Cells ◽  
B Cell ◽  
Bacterial Infections ◽  
Relative Proportion ◽  
Post Treatment ◽  
Latent Tb ◽  
Latent Tb Infection

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.

scholarly journals Recent Progress in Diagnosis Methods for Latent Tuberculosis Infection and Its Clinical Applications

2015 ◽  
Vol 4 (3) ◽  
pp. 69-74
Author(s):  
Ling Zhou
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Recent Progress ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Interferon Γ ◽  
Clinical Applications ◽  
Active Tuberculosis ◽  
Advantages And Disadvantages ◽  
Latent Tb ◽  
Latent Tb Infection

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.

scholarly journals Characterization of Host and Microbial Determinants in Individuals with Latent Tuberculosis Infection Using a Human Granuloma Model

mBio ◽  
2015 ◽  
Vol 6 (1) ◽  
Author(s):  
Evelyn Guirado ◽  
Uchenna Mbawuike ◽  
Tracy L. Keiser ◽  
Jesus Arcos ◽  
Abul K. Azad ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Immune Status ◽  
Host Immune Response ◽  
Granuloma Formation ◽  
Content Type ◽  
Transcriptional Signature ◽  
Latent Tb ◽  
Latent Tb Infection

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.

scholarly journals Characterization of Mycobacterium tuberculosis-specific Th22 cells and the effect of tuberculosis disease and HIV co-infection

2020 ◽  
Author(s):  
Mohau S. Makatsa ◽  
F. Millicent A. Omondi ◽  
Rubina Bunjun ◽  
Robert J. Wilkinson ◽  
Catherine Riou ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Latent Tuberculosis ◽  
Th22 Cells ◽  
Distinct Subset ◽  
Increased Risk ◽  
Ifn Γ

ABSTRACTThe development of a highly effective tuberculosis (TB) vaccine is likely dependent on our understanding of what constitutes a protective immune response to TB. Accumulating evidence suggests that CD4+ T cells producing IL-22, a distinct subset termed ‘Th22’ cells, may contribute to protective immunity to TB. Thus, we characterized Mycobacterium tuberculosis (Mtb)-specific Th22 (and Th1 and Th17) cells in 72 individuals with latent tuberculosis infection (LTBI) or TB disease, with and without human immunodeficiency virus (HIV)-1 infection. We investigated the functional properties (IFN-γ, IL-22 and IL-17 production), memory differentiation (CD45RA, CD27 and CCR7) and activation profile (HLA-DR) of Mtb-specific CD4+ T cells. In HIV-uninfected individuals with LTBI, we detected abundant IFN-γ producing CD4+ T cells (median: 0.93%) and IL-22-producing CD4+ T cells (median: 0.46%) in response to Mtb. The frequency of IL-17 producing CD4+ T cells was much lower, at a median of 0.06%. Consistent with previous studies, IL-22 was produced by a distinct subset of CD4+ T cells and not co-expressed with IL-17. Mtb-specific IL-22 responses were markedly reduced (median: 0.08%) in individuals with TB disease and HIV co-infection compared to IFN-γ responses. Mtb-specific Th22 cells exhibited a distinct memory and activation phenotype compared to Th1 and Th17 cells. Furthermore, Mtb-specific IL-22 was produced by conventional CD4+ T cells that required T cell receptor (TCR) engagement. In conclusion, we confirm that Th22 cells contribute substantially to the immune response to TB. Depletion of Mtb-specific Th22 cells during HIV co-infection may contribute to increased risk of TB disease.

scholarly journals Tuberculosis-Associated MicroRNAs: From Pathogenesis to Disease Biomarkers

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2160
Author(s):  
Alessandro Sinigaglia ◽  
Elektra Peta ◽  
Silvia Riccetti ◽  
Seshasailam Venkateswaran ◽  
Riccardo Manganelli ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Recent Literature ◽  
Latent Tuberculosis Infection ◽  
Adaptive Immune Response ◽  
Latent Tuberculosis ◽  
Host Immune System ◽  
Disease Biomarkers ◽  
Adaptive Immune ◽  
Potential Use

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the most lethal infectious diseases with estimates of approximately 1.4 million human deaths in 2018. M. tuberculosis has a well-established ability to circumvent the host immune system to ensure its intracellular survival and persistence in the host. Mechanisms include subversion of expression of key microRNAs (miRNAs) involved in the regulation of host innate and adaptive immune response against M. tuberculosis. Several studies have reported differential expression of miRNAs during active TB and latent tuberculosis infection (LTBI), suggesting their potential use as biomarkers of disease progression and response to anti-TB therapy. This review focused on the miRNAs involved in TB pathogenesis and on the mechanism through which miRNAs induced during TB modulate cell antimicrobial responses. An attentive study of the recent literature identifies a group of miRNAs, which are differentially expressed in active TB vs. LTBI or vs. treated TB and can be proposed as candidate biomarkers.

scholarly journals Targeting Non-Replicating Mycobacterium tuberculosis and Latent Infection: Alternatives and Perspectives (Mini-Review)

2021 ◽  
Vol 22 (24) ◽  
pp. 13317
Author(s):  
Anna Egorova ◽  
Elena G. Salina ◽  
Vadim Makarov
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Small Molecules ◽  
Drug Targets ◽  
Latent Infection ◽  
Early Stage ◽  
Control Strategies ◽  
Latent Tuberculosis ◽  
Ltbi Treatment ◽  
Latent Tb ◽  
Current Guidelines

Latent tuberculosis infection (LTBI) represents a major challenge to curing TB disease. Current guidelines for LTBI management include only three older drugs and their combinations—isoniazid and rifamycins (rifampicin and rifapentine). These available control strategies have little impact on latent TB elimination, and new specific therapeutics are urgently needed. In the present mini-review, we highlight some of the alternatives that may potentially be included in LTBI treatment recommendations and a list of early-stage prospective small molecules that act on drug targets specific for Mycobacterium tuberculosis latency.

scholarly journals Expression of Cathelicidin LL-37 during Mycobacterium tuberculosis Infection in Human Alveolar Macrophages, Monocytes, Neutrophils, and Epithelial Cells

2007 ◽  
Vol 76 (3) ◽  
pp. 935-941 ◽  
Author(s):  
Bruno Rivas-Santiago ◽  
Rogelio Hernandez-Pando ◽  
Claudia Carranza ◽  
Esmeralda Juarez ◽  
Juan Leon Contreras ◽  
...  
Keyword(s):  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Epithelial Cells ◽  
Innate Immune Response ◽  
Alveolar Macrophages ◽  
Mycobacterial Infection ◽  
Innate Immune ◽  
Tuberculosis Infection ◽  
Mycobacterium Tuberculosis Infection ◽  
Peptide Expression

ABSTRACT The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.

scholarly journals Performance of an interferon-gamma release assay for diagnosing latent tuberculosis infection in children

2007 ◽  
Vol 136 (9) ◽  
pp. 1179-1187 ◽  
Author(s):  
K. OKADA ◽  
T. E. MAO ◽  
T. MORI ◽  
T. MIURA ◽  
T. SUGIYAMA ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Latent Tuberculosis ◽  
Mycobacterial Infection ◽  
Sputum Smear ◽  
Interferon Gamma Release Assay ◽  
Test Results ◽  
Positive Rate ◽  
Release Assay ◽  
Latent Tb ◽  
Latent Tb Infection

SUMMARYNewly developed interferon-gamma release assays have become commercially available to detect tuberculosis (TB) infection in adults. However, little is known about their performance in children. We compared test results between the QuantiFERON-TB® Gold test (QFT) and tuberculin skin test (TST) in young children living with pulmonary TB patients in Cambodia. Of 195 children tested with both QFT and TST, the TST-positive rate of 24% was significantly higher than the QFT-positive rate of 17%. The agreement between the test results was considerable (κ-coefficient 0·63). Positive rates increased from 6% to 32% for QFT and from 15% to 43% for TST, according to the sputum smear grades of the index cases. The presence of Bacille Calmette-Guérin (BCG) scars did not significantly affect the results of TST or QFT in a logistic regression analysis. In conclusion, QFT can be a substitute for TST in detecting latent TB infection in childhood contacts aged ⩽5 years, especially in those who may have a false-positive TST due to BCG vaccination or non-tuberculous mycobacterial infection.

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