Helminthic infections afflict over 1.5 billion people worldwide, while Mycobacterium tuberculosis infects one third of the world's population, resulting in 2 million deaths per year. Although tuberculosis and helminthic infections coexist in many parts of the world, and it has been demonstrated that the T-helper 2 and T-regulatory cell responses elicited by helminths can affect the ability of the host to control mycobacterial infection, it is still unclear whether helminth infections in fact affect tuberculosis disease. In this review article, current progress in the knowledge about the immunomodulation induced by helminths to diminish the protective immune responses to bacille Calmette-Guerin vaccination is reviewed, and the knowledge about the types of immune responses modulated by helminths and the consequences for tuberculosis are summarized. In addition, recent data supporting the significant reduction of both M. tuberculosis antigen-specific Toll-like receptor (TLR) 2 and TLR9 expression, and pro-inflammatory cytokine responses to TLR2 and TLR9 ligands in individuals with M. tuberculosis and helminth co-infection were discussed. This examination will allow to improve understanding of the immune responses to mycobacterial infection and also be of great relevance in combating human tuberculosis.
Animals ; Coinfection ; Helminthiasis/complications/*immunology/parasitology ; Helminths/*immunology ; Humans ; Mycobacterium tuberculosis/*immunology ; Tuberculosis/complications/*immunology/microbiology

Mycobacterium tuberculosis (Mtb) is an intracellular pathogen that infects alveolar macrophages following aerosol transmission. Lung macrophages provide a critical intracellular niche that is required for Mtb to establish infection in the human host. This parasitic relationship is made possible by the capacity of Mtb to block phagosome maturation following entry into the host macrophage, creating an environment that supports bacillary replication. Apoptosis is increasingly understood to play a role in host defense against intracellular pathogens including viruses, fungi, protozoa and bacteria. In the last 15 years an understanding of the role that macrophage apoptosis plays in TB has begun to emerge. Here we review the history and current state of the art of this topic and we offer a model of the macrophage-pathogen interaction that takes into the account the complexities of programmed cell death and the relationship between various death signaling pathways and host defense in TB.
Animals ; Apoptosis/*immunology ; Humans ; Macrophages/*cytology/*microbiology ; Mycobacterium tuberculosis/*immunology ; Tuberculosis, Pulmonary/*immunology

This study aimed to establish human IFN-gamma (hIFN-gamma) in vitro release assay and to apply it in diagnosis of human tuberculosis. Human IFN-gamma gene was cloned and expressed in Escherichia coli. The recombinant hIFN-gamma was purified and used as immunogen to immunize mice and rabbits respectively. Monoclonal and polyclonal antibodies were respectively developed and a sandwich ELISA was established. The heparized whole blood from 111 active tuberculosis patients and 292 clinical healthy controls were collected. The blood was stimulated with tuberculosis specific fused antigen ESAT-6/CFP-10 and the plasma was collected for IFN-gamma detection. The sensitivity for tuberculosis diagnosis was 95.5%, whereas the positive detection rate for the healthy controls was 16.7%. There was a significant difference between the patients and healthy controls (P<0.01) indicating that this assay had a high sensitivity and specificity, and thus could be promising in tuberculosis diagnosis.
Animals ; Antibodies, Monoclonal ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interferon-gamma ; immunology ; secretion ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis ; immunology ; Rabbits ; T-Lymphocytes ; immunology ; Tuberculosis ; diagnosis ; immunology

Expression microarray was employed in this study to investigate whether the ion channels and their regulatory elements encoding genes participate in the immune response to Mycobacterium tuberculosis infection. The results of a virulent strain were compared with those of the clinically isolated strains. The data demonstrate that K(+), Na(+), Ca(2+) and Cl(-) channels and their regulatory elements, such as the G protein, receptor and second messenger, protein kinase and protein phosphatase were involved in the immune reaction. The clinical strain affected more types of ion channels and respective regulatory elements. The data provides clues for further scrutiny into the role of ion channels and related elements in the interaction between Mycobacterium tuberculosis and host macrophage.
Gene Expression Regulation ; Humans ; Ion Channels ; genetics ; Macrophages ; immunology ; microbiology ; Mycobacterium tuberculosis ; pathogenicity ; Regulatory Elements, Transcriptional ; Tuberculosis ; genetics ; immunology ; microbiology

Tuberculosis is a chronic infectious disease caused by Mycobacterium (M.) tuberculosis. Innate immunity plays an important role in the response to M. tuberculosis. Toll-like receptors (TLRs) are important pattern recognition receptors in innate immunity. TLRs serve as switches that play decisive roles in identifying pathogens-related components. Previous studies found that TLR1, TLR2, TLR4, TLR9 were essential to promote the development of innate immune responses. The SNPs of rs4833095, rs5743618, rs3923647 of TLR1, rs57473708, rs3804099 of TLR2 and rs352139, rs5743836 of TLR9 were closely related to the susceptibility of tuberculosis in some populations. And there appeared certain relationship between the polymorphisms of TLR3, TLR6, TLR7, TLR8, TLR10 and the susceptibility of tuberculosis. The normal function of TLRs ensures the body's normal immune response to M. tuberculosis. The diversity of TLRs genes allows different individuals to respond differently to the same pathogen. Studies targeting on the relationship between single nucleotide polymorphism in TLRs and susceptibility to tuberculosis can predict the susceptibility to tuberculosis in some populations, as well as discover new drugs targets.
Genetic Predisposition to Disease ; Humans ; Mycobacterium tuberculosis ; Polymorphism, Single Nucleotide ; Research/trends* ; Signal Transduction/immunology* ; Toll-Like Receptors/genetics* ; Tuberculosis/immunology*

As the dominant antigens, early secreted antigenic target 6 (ESAT6, E6) and culture filtrate protein 10 (CFP10, C10) had once been the focus of tuberculosis (TB) vaccine due to their capability of inducing strong cell immune response in the host. They are also endowed with promising future of prevention against and diagnosis of TB. In this review, we systematically introduce recent research progress of E6 and C10, especially in structure-function, biological characteristics, protein expression and secretion, host immunity and vaccine development, and the prospects of their application are also discussed.
Antigens, Bacterial ; chemistry ; genetics ; immunology ; Bacterial Proteins ; chemistry ; genetics ; immunology ; Humans ; Immunodominant Epitopes ; immunology ; Molecular Biology ; Peptide Fragments ; chemistry ; genetics ; immunology ; Tuberculosis Vaccines ; genetics ; immunology ; Vaccines, DNA ; immunology

Rapid and accurate diagnosis of Mycobacterium tuberculosis in symptomatic patients is important for the global tuberculosis control strategies. Despite the enormous global burden of TB and the overall low rates of case detection worldwide, conventional diagnostic approaches have relied on tests that have several major limitations until recently, and standard treatment regimens have not changed for more than 30yr. Recently remarkable progress in the basic science of immunology and molecular biology is ongoing to upgrade the speed and quality of diagnostic service and probably the strategy of the treatment of tuberculosis. In this review, we focus on strengths and limitations of newer tests that are available for the diagnosis of latent and active tuberculosis and the rapid detection of drug resistance, specifically, tests to measure of IFN-gamma released from T-cell by stimulation with M. tuberculosis specific antigens, tests to amplify the nucleic acid for identification of M. tuberculosis complex, and rapid tests to detect drug resistance.
Allergy and Immunology ; Diagnosis ; Diagnostic Services ; Drug Resistance ; Humans ; Molecular Biology ; Mycobacterium tuberculosis* ; Mycobacterium* ; T-Lymphocytes ; Tuberculosis

OBJECTIVETo evaluate the clinical significance of using T cell responses to three RD1-encoded gene products for diagnosis of mycobacterium tuberculosis (MTB) infection.

METHODSWe used ex vivo gamma-interferon enzyme-linked immunospot assays to test T cell responses to three novel gene products encoded by RD1 (Rv3873, Rv3878, and Rv3879c) in 49 patients (TB group) who were bacteriologically confirmed by positive cultures for MTB and 38 healthy BCG-vaccinated donors (control group). Forty-nine overlapping peptides were tested in all participants.

RESULTSThe T cell response rates to Rv3873, Rv3878, and Rv3879c were 53% (95% CI: 39%-67%), 35% (95% CI: 22%-48%), and 45% (95% CI: 31%-57%), respectively, in the TB group and were 7.9%, 2.6%, and 2.6%, respectively, in the control group.

CONCLUSIONRv3879c peptides can be candidates for inclusion in new T cell-based tests for MTB infection.

Adult ; Antigens, Bacterial ; immunology ; BCG Vaccine ; immunology ; Bacterial Proteins ; immunology ; Female ; Humans ; Immunoassay ; Interferon-gamma ; immunology ; Male ; Middle Aged ; Mycobacterium tuberculosis ; immunology ; T-Lymphocytes ; immunology ; Tuberculosis ; diagnosis ; immunology ; Young Adult

Antigen Rv2628 of Mycobacterium tuberculosis is associated with latent tuberculosis infection. In this study, Rv2628 was prokaryotic expressed and purified, its immunological characteristics was evaluated with macrophage cell line RAW264.7 and BALB/c mice. The results show that Rv2628 was mainly expressed in form of inclusion body confirmed by SDS-PAGE, and could react with rabbit anti-H37Rv polyclonal antibody detected by Western blotting assay, indicating that the protein had an effective immunoreactivity. The interactions between Rv2628 and macrophage cell line RAW264.7 confirmed that it could effectively induce cells to produce pro-inflammatory cytokines, the relative expression level of IL-6 mRNA was higher than the control group in 1-12 h. BALB/c mice were subcutaneously immunized with Rv2628 protein, the production of IFN-gamma and IL-4 in the spleen cells was determined by Sandwich ELISA, in the Rv2628 immunized group, the level of IFN-gamma was significantly higher than that of IL-4 (P < 0.000 1). It indicated the protein induced Th1-tendency immune responses. At the same time, Rv2628(11-30) peptide used as coating antigen, the murine serum antibody titer detected by indirect-ELISA was 1:1 600, which demonstrated that Rv2628 could also induce humoral immune responses. In summary, Rv2628 could induce specific pro-inflammatory cytokines, affectively induce strongly Th1-tendency immune response and humoral response, it could be a potential target for developing subunit vaccine against TB. In addition, it laid foundation for probing the cross-talk between M. tb and host.
Animals ; Antibodies, Bacterial ; blood ; Antigens, Bacterial ; immunology ; Cell Line ; Electrophoresis, Polyacrylamide Gel ; Interferon-gamma ; immunology ; Interleukin-4 ; immunology ; Interleukin-6 ; immunology ; Macrophages ; immunology ; Mice ; Mice, Inbred BALB C ; Mycobacterium tuberculosis ; Th1 Cells ; immunology ; Tuberculosis ; immunology

OBJECTIVETo detect the expression of Mycobacterium tuberculosis secreted protein Ag85B in paraffin-embedded tissues by immunohistochemistry (IHC), and to evaluate its application in the pathological diagnosis of tuberculosis.

METHODSOne hundred and five tuberculosis specimens (54 pulmonary tuberculosis, 51 lymph nodal tuberculosis) and 51 specimens of other diseases (8 lung cancer, 10 pulmonary abscess, 10 bronchiectasis, 7 lymphoma, 5 necrotizing lymphadenitis, 4 reactive hyperplasia lymphoid, and 7 sarcoidosis) were collected from January 2012 to July 2013 from Beijing Chest Hospital, Capital Medical University. One-step IHC was performed on paraffin-embedded tissues using antibody directed against Ag85B.

RESULTSIHC and Ziehl-Neelsen (ZN) acid-fast staining showed that distribution and intensity of Ag85B expression were concordant with the distribution and number of acid-fast bacilli. IHC showed significantly higher sensitivity than ZN staining (50.5%, 53/105 vs. 31.4%, 33/105; χ² = 7.877, P = 0.005). The combined sensitivity of IHC and ZN staining was 59.0%. Moreover, oil immersion was not necessary for IHC, allowing more rapid diagnosis.

CONCLUSIONIHC detection of Ag85B is a simple method with higher sensitivity than ZN staining, and demonstrated good value in the pathological diagnosis of tuberculosis.

Acyltransferases ; metabolism ; Antigens, Bacterial ; metabolism ; Biomarkers ; metabolism ; Bronchiectasis ; diagnosis ; immunology ; Humans ; Immunohistochemistry ; Lymphadenitis ; diagnosis ; immunology ; Mycobacterium tuberculosis ; immunology ; Sarcoidosis ; diagnosis ; Staining and Labeling ; Tuberculosis, Lymph Node ; diagnosis ; immunology ; Tuberculosis, Pulmonary ; diagnosis ; immunology