Antibody-Fab and -Fc features promote restriction.

the causative agent of tuberculosis (TB), is a leading cause of death by an infectious disease globally, with no efficacious vaccine. Antibodies are implicated in control, but the mechanisms of antibody action remain poorly understood. We assembled a library of TB monoclonal antibodies (mAb) and screened for the ability to restrict in mice, identifying protective antibodies targeting known and novel antigens.

Diagnostic markers reflecting dysregulation of the host response in the transition to tuberculosis disease.

Sustained control of Mycobacterium tuberculosis infection without evidence of disease is based on a finely tuned balance between pro- and anti-inflammatory responses. Loss of this balance leads to tuberculosis (TB) disease, in which exacerbated myeloid and neutrophil activation is common. Proteomic and transcriptomic assessment of the host response can detect increasing immune activation associated with TB disease progression several months before clinical disease.

Correction: Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.

[This corrects the article DOI: 10.1371/journal.pone.

From simple to complex: Protein-based biomarker discovery in tuberculosis.

Tuberculosis (TB) is a deadly infectious disease that affects millions of people globally. TB proteomics signature discovery has been a rapidly growing area of research that aims to identify protein biomarkers for the early detection, diagnosis, and treatment monitoring of TB. In this review, we have highlighted recent advances in this field and how it is moving from the study of single proteins to high-throughput profiling and from only using proteomics to include additional types of data in multi-omics studies.

A protein signature associated with active tuberculosis identified by plasma profiling and network-based analysis.

Annually, approximately 10 million people are diagnosed with active tuberculosis (TB), and 1.4 million die of the disease. If left untreated, each person with active TB will infect 10-15 new individuals.

Immunological hyporesponsiveness in tuberculosis: The role of mycobacterial glycolipids.

Glycolipids constitute a major part of the cell envelope of (Mtb). They are potent immunomodulatory molecules recognized by several immune receptors like pattern recognition receptors such as TLR2, DC-SIGN and Dectin-2 on antigen-presenting cells and by T cell receptors on T lymphocytes. The Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic relatives, phosphatidylinositol mannosides (PIMs) and lipomannan (LM), as well as other Mtb glycolipids, such as phenolic glycolipids and sulfoglycolipids have the ability to modulate the immune response, stimulating or inhibiting a pro-inflammatory response.

Early risk assessment in paediatric and adult household contacts of confirmed tuberculosis cases by novel diagnostic tests (ERASE-TB): protocol for a prospective, non-interventional, longitudinal, multicountry cohort study.

Introduction: The WHO End-TB Strategy calls for the development of novel diagnostics to detect tuberculosis (TB) earlier and more accurately. Better diagnostics, together with tools to predict disease progression, are critical for achieving WHO End-TB targets. The arly isk ssessment in TB Contacts by new diagnotic tsts (ERASE-TB) study aims to evaluate novel diagnostics and testing algorithms for early TB diagnosis and accurate prediction of disease progression among household contacts (HHCs) exposed to confirmed index cases in Mozambique, Tanzania and Zimbabwe.

Performance of novel antibodies for lipoarabinomannan to develop diagnostic tests for Mycobacterium tuberculosis.

Lipoarabinomannan (LAM), a component of the Mycobacterium tuberculosis (MTB) cell wall, is detectable in the urine of MTB infected patients with active tuberculosis (TB). LAM-specific antibodies (Igs) have been developed by a variety of traditional and recombinant methods for potential use in a rapid diagnostic test (RDT). We evaluated the analytical performance of the TB LAM Igs to identify pairs that offer superior performance over existing urine LAM tests.

High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids.

Upon infection with (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored.

CD4 T cell proliferative responses to PPD and CFP-10 associate with recent M. tuberculosis infection.

Interferon-γ release assays cannot differentiate latent from active tuberculosis (TB), nor identify the recently infected with increased risk of active disease. The objective of this study was to identify biomarkers of recent infection following exposure to tuberculosis, to increase the positive predictive value for incipient TB. Contacts to patients with pulmonary TB were tested repeatedly with interferon-γ release assays and flow-cytometry.

Stabilization of blood for long-term storage can affect antibody-based recognition of cell surface markers.

Whole-blood fixation provides a rapid and simplified method for cell preservation compared to isolation of peripheral blood mononuclear cells (PBMCs). This can be especially important for sample acquisition and storage in resource-limited settings. However, some caveats have been reported, such as reduced cell marker recognition.

Lipoarabinomannan in Active and Passive Protection Against Tuberculosis.

Glycolipids of the cell wall of (Mtb) are important immunomodulators in tuberculosis. In particular, lipoarabinomannan (LAM) has a profound effect on the innate immune response. LAM and its structural variants can be recognized by and activate human CD1b-restricted T cells, and emerging evidence indicates that B cells and antibodies against LAM can modulate the immune response to Mtb.

A new mathematical model to identify contacts with recent and remote latent tuberculosis.

Tuberculosis (TB) elimination programmes need to target preventive treatment to groups with an increased risk of TB activation, such as individuals with a latent tuberculosis infection (LTBI) acquired recently. Current diagnostic tests for LTBI have poor predictive values for TB activation and there is, at present, no reference method to evaluate new LTBI diagnostic and prognostic tools. Thus, our objective was to develop a mathematical model, independent of currently available diagnostic tests, to estimate the individual probability of recent and/or remote LTBI.

Biomarkers for tuberculosis: the case for lipoarabinomannan.

Tuberculosis (TB) is considered the most onerous of infectious diseases according to recent reports from the World Health Organization. Available tests for TB diagnosis present severe limitations, and a reliable point-of-care (POC) diagnostic test does not exist. Neither is there a test to discern between the different stages of TB, and in particular to predict which patients with infection and no clinical signs are more at risk of advancing to overt disease.

Deciphering the molecular basis of mycobacteria and lipoglycan recognition by the C-type lectin Dectin-2.

Dectin-2 is a C-type lectin involved in the recognition of several pathogens such as Aspergillus fumigatus, Candida albicans, Schistosoma mansonii, and Mycobacterium tuberculosis that triggers Th17 immune responses. Identifying pathogen ligands and understanding the molecular basis of their recognition is one of the current challenges. Purified M.

Geospatial distribution of Mycobacterium tuberculosis genotypes in Africa.

Objective: To investigate the distribution of Mycobacterium tuberculosis genotypes across Africa.

Methods: The SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, of M. tuberculosis from Africa.

Genetic diversity and potential routes of transmission of Mycobacterium bovis in Mozambique.

Bovine tuberculosis is a zoonotic disease with largely unknown impact in Africa, with risk factors such as HIV and direct contact with animals or consumption of Mycobacterium bovis infected animal products. In order to understand and quantify this risk and design intervention strategies, good epidemiological studies are needed. Such studies can include molecular typing of M.

Human leukocyte antigen class 1 genotype distribution and analysis in persons with active tuberculosis and household contacts from Central Uganda.

Background: To determine the distribution of Human leukocyte antigen (HLA) class I genotypes in a Ugandan population of persons with tuberculosis (TB) and establish the relationship between class I HLA types and Mycobacterium tuberculosis (MTB) disease.

Methods: Blood samples were drawn from HIV negative individuals with active TB and HIV negative household controls. DNA was extracted from blood samples and HLA typed by the polymerase chain reaction-sequence specific primer method.

Translational Research for Tuberculosis Elimination: Priorities, Challenges, and Actions.

Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035.

Association between human leukocyte antigen class II and pulmonary tuberculosis due to mycobacterium tuberculosis in Uganda.

Background: Mycobacterium tuberculosis (Mtb) is reported to infect about a third of the world's population but only 10% are thought to develop active tuberculosis (TB) disease. Host immunity regulated by human leukocyte antigens (HLA) is an important determinant of the outcome of the disease. Here we investigate HLA class II gene polymorphisms in susceptibility to TB, and whether particular HLA class II alleles were associated with TB in Uganda.

Lipoarabinomannan, and its related glycolipids, induce divergent and opposing immune responses to Mycobacterium tuberculosis depending on structural diversity and experimental variations.

Exposure to Mycobacterium tuberculosis (Mtb) may lead to active or latent tuberculosis, or clearance of Mtb, depending essentially on the quality of the host's immune response. This response is initiated through the interaction of Mtb cell wall surface components, mostly glycolipids, with cells of the innate immune system, particularly macrophages (Mφs) and dendritic cells (DCs). The way Mφs and DC alter their cytokine secretome, activate or inhibit different microbicidal mechanisms and present antigens and consequently trigger the T cell-mediated immune response impacts the host immune response against Mtb.

Predominance of Uganda genotype of Mycobacterium tuberculosis isolated from Ugandan patients with tuberculous lymphadenitis.

Background: In Uganda, the emerging Uganda genotype of Mycobacterium tuberculosis is the most common cause of pulmonary tuberculosis (PTB), and accounts for up to 70% of isolates. Extrapulmonary TB (EPTB) is less studied in Uganda.

Methods: Molecular characterization using deletion analysis and spoligotyping was performed on 121 M.

A sensitive urinary lipoarabinomannan test for tuberculosis.

We have previously developed a diagnostic test for tuberculosis based on detection of mycobacterial lipoarabinomannan (LAM) in urine. The method depended on a laborious concentration step. We have now developed an easy to perform test based on a magnetic immunoassay platform, utilizing high avidity monoclonal antibodies for the detection of LAM in urine.