Role In Tuberculosis Infection Research Articles

Identification of immune subtypes associated with neutrophils in tuberculosis infection based on weighted gene co-expression network analysis

Tuberculosis (TB) is caused by Mycobacterium tuberculosis and is a major global health concern. Neutrophils play a significant role in TB infection and patient outcomes. This study aimed to identify gene modules associated with neutrophil infiltration in TB samples using WGCNA. Gene ontology and enrichment analyses were performed, and a random forest model was constructed to identify differentially expressed genes. K-means clustering was used to classify samples into subtypes, and immune-related scores, PD-L1 expression, HLA expression, and gene enrichment analysis were evaluated. The blue module showed significant correlation with neutrophils and enrichment in immune-related processes. The model exhibited good classification performance, and subtype 1 demonstrated higher immune-related scores, PD-L1 expression, HLA class I molecule expression, and immune-related pathway enrichment. These findings enhance our understanding of TB pathogenesis and provide potential targets for diagnosis and treatment strategies.

Probiotic-Based Therapy for Active Tuberculosis Infection: The Role of Gut-Lung Axis and Granulocyte Macrophage-Colony Stimulating Factor

Tuberculosis is a global health problem with a total of 1.4 million cases in 2015. Over the last decade, several studies have demonstrated the potential role of gut-lung axis in the treatment of tuberculosis. The exact mechanism of the gut-lung axis on tuberculosis is still unknown, however modulation of the gut-lung axis can be performed via probiotic administration. The administered probiotics are capable of inducing an immunomodulating effect which helps in the process of tuberculosis infection. One of the molecules that can be activated with probiotics and plays a role in tuberculosis infection is granulocyte macrophage-colony stimulating factor (GM-CSF). GM-CSF can control intracellular production of M. tuberculosis, inflammation in granulomas, and lung tissue reparation. This article aimed to explore the role of the gut-lung axis, GM-CSF, and the potential of probiotic-based therapy on active tuberculosis infection. It was found that probiotics mediate the immune response via the activation of several inflammatory cytokines and interleukins related to lung infection, but not directly with the tuberculosis pathogen. Thus, probiotic-based therapy has the potential to increase immunity during active tuberculosis infection. Further studies to explore the other mechanisms of the gut-lung axis against tuberculosis through probiotic administration need to be performed.

Estimation of Serum Copper and Zinc Levels among Tuberculosis Patients in Khartoum State

Background: Trace elements play an important role in tuberculosis infection because their deficiencies can be associated with impaired immunity. The aim to assessment the serum copper and zinc levels among the tuberculosis patients in Khartoum state Material: This is cross sectional study was conducted in Aboanja hospital in Khartoum state during the period from November 2016_January 2017.Citrated samples were collected from 100 study group , 50 tuberculosis patients , and 50 apparently healthy Individuals, Serum level of Zinc and Copper was measured by atomic absorption spectrometry. Result: The result is the mean level of Zinc in tuberculosis patients were significant decreased when compared with control group (P. value= <0.001) and also the mean level of Copper in tuberculosis patients significant increase when compared with group ( P. value = <0.001). Conclusion: This study showed significant decrease in level of Zinc and increase in level of Copper once compared with control group among tuberculosis patients. Keywords: Copper, Impaired immunity, Trace element, Tuberculosis, Zinc

Investigation of the relationship of latent tuberculosis infection with the development of myeloid and lymphoblastic leukemia

Annotation. The relationship between tuberculosis infection and hemoblastosis has attracted the attention of physicians and has been the basis for a wide variety of assumptions. In the second half of the XIX century, there was expressed an opinion about the unique nature of these pathologies. They explained this phenomenon as the immunochemical affinity of specific tumor and mycobacterial antigens, but not as a result of the persistence of mycobacterium tuberculosis (MBT). The aim of the study was to investigate the association of latent tuberculosis infection and oncogenesis, in particular with leukemias. From transplantable human myeloblasts with acute myeloid leukemia (Kasumi-1) and T-lymphocytes with T-lymphoblastic leukemia (Jurkat), including 0.22 μm filtrate of their lysates were isolated from mycobacterium tuberculosis (MBT) with deficient cell wall (CWD). During primary microscopy, the MBT was found mainly in the form of coccoid. The isolated coccoid Kasumi and Jurkat had close antigen affinity and shared antigens with typical MBT. After prolonged incubation with the growth promoter, not only CWD MBT was isolated from all lysates and filtrates, but isolates with identical morphology and antigenic composition were obtained. This strongly suggested that the MBT and their modified forms could be associated with various types of leukemia. Moreover, the affinity of FLK-BLV isolates with blood of people with latent tuberculosis infection, cattle tuberculosis, CWD forms M. bovis and M. tuberculosis was determined, confirming the role of tuberculosis infection in the development of various forms of the disease depending on the host genome, as well as the features of the adaptive reactions of the infectious agent. In particular, after destruction by ultrasound and filtration through Amicon Ultracel® 100 K and Millex® GP 0.22 μm, their filtrates gave an increase in the number of CWD MBT with acid-resistant elements and had the same antigenic composition, including the original isolates. The long-term incubation of the test material in the growth promoter and numerous transplants on the adapted MyCel DW medium played a major role in the allocation of CWD.

Association between the mannose-binding lectin (MBL)-2 gene variants and serum MBL with pulmonary tuberculosis: An update meta-analysis and systematic review

In recent years, many studies have demonstrated that the MBL-2 gene polymorphisms may be associated with pulmonary tuberculosis (PTB) susceptibility. Moreover, some studies have shown that serum MBL levels were influenced by the MBL-2 gene polymorphisms and that it plays an important role in tuberculosis infection. However, the results of these studies were inconsistent and underpowered. The current meta-analysis and systematic review aimed to evaluate the association between the MBL-2 gene polymorphisms and serum MBL levels with PTB. Finally, 30 eligible articles were included in the study. The overall results indicated that the MBL-2 rs1800450 (54 A/B) and rs5030737 (52 A/D) polymorphisms were risk factors for PTB, but the MBL-2 rs1800451 (57 A/C) and rs7095891 (+4 P/Q) polymorphisms as protective factors against PTB. No associations were found in the other three polymorphisms (exon 1, rs7096206 (−221 X/Y), and rs11003125 (−550 H/L) of the MBL-2 gene. In addition, we could not detect any significant differences between haplotypes among PTB patients and healthy controls. More important, the meta-analysis results indicated that the serum MBL levels in patients with PTB were significantly lower than those in healthy controls (SMD = 0.43, 95% CI = 0.33–0.52). This study suggested that the MBL-2 gene polymorphisms may be involved in the pathogenesis of PTB, and serum MBL may be a biomarker for the diagnosis of PTB. More rigorous research is needed in the future to confirm these findings further.

Elevated Cyclic AMP Inhibits Mycobacterium tuberculosis-Stimulated T-cell IFN-γ Secretion Through Type I Protein Kinase A.

Cyclic adenosine monophosphate (cAMP) is critical in immune regulation, and its role in tuberculosis infection remains unclear. We determined the levels of cAMP in peripheral blood mononuclear cells (PBMC) from tuberculosis patients and the mechanisms for cAMP suppression of IFN-γ production. PBMC from tuberculosis patients contained significantly elevated cAMP than latent tuberculosis infected subjects (LTBI), with an inverse correlation with IFN-γ production. Consistent with this, the expression of cAMP response element binding protein (CREB), activating transcription factor (ATF)-2 and c-Jun were reduced in tuberculosis patients compared with LTBI. PKA type I specific cAMP analogs inhibited Mtb-stimulated IFN-g production by PBMC through suppression of Mtb-induced IFN-γ promoter binding activities of CREB, ATF-2, and c-Jun and also miR155, the target miRNA of these transcription factors. Neutralizing both IL-10 and TGF-β1 or supplementation of IL-12 restored cAMP-suppressed IFN-g production. We conclude that increased cAMP inhibits IFN-g production through PKA type I pathway in tuberculosis infection.

Evaluation of the relationship between MARCO and CD36 single-nucleotide polymorphisms and susceptibility to pulmonary tuberculosis in a Chinese Han population

BackgroundGene polymorphisms impact greatly on a person’s susceptibility to pulmonary tuberculosis (PTB). Macrophage receptor with collagenous structure (MARCO) and CD36 are two scavenger receptors (SRs) that can recognize Mycobacterium tuberculosis (Mtb) and play a key role in tuberculosis infection. Gene polymorphisms of MARCO and CD36 may contribute to tuberculosis risk.MethodsTo investigate whether genetic polymorphisms of MARCO and CD36 are associated with susceptibility to PTB, genomic DNA samples from patients (n = 202) and healthy controls (n = 216) were collected and analyzed by polymerase chain reaction with high-resolution melting analysis.ResultsWe studied two single nucleotide polymorphisms (SNPs) in MARCO (rs12998782 and rs17009726) and three SNPs in CD36 (rs1194182, rs3211956 and rs10499859). Rs12998782 (P = 0.018) might be associated with susceptibility to PTB. Rs1194182 (P < 0.01) and rs10499859 (P < 0.001) might be associated with resistance to PTB. Rs17009726 and rs3211956 were not associated with susceptibility/resistance to PTB.ConclusionsThese data showed that MARCO rs12998782 may increase PTB risk while two SNPs of CD36, rs1194182 and rs10499859 may reduce the risk, indicating MARCO and CD36 as important receptors in response to PTB.

TNF-&amp;lt;i&amp;gt;α&amp;lt;/i&amp;gt; (&amp;lt;i&amp;gt;Tumor Necrosis Factor Alpha&amp;lt;/i&amp;gt;) and iNOS (&amp;lt;i&amp;gt;Inducible Nitric Oxide Synthase&amp;lt;/i&amp;gt;) Expression in Rat Brain Infected by &amp;lt;i&amp;gt;Mycobacterium tuberculosis&amp;lt;/i&amp;gt; Strain H37RV

Tuberculosis is an infectious disease caused by the Mycobacterium tuberculosis. Mycobacterium tuberculosis will form the primary focus or Ghon focus in the lungs of infected people. The primary focus can break and get into the bloodstream and/or lymph to the entire body, including the central nervous system, especially the brain. Tuberculosis infection in the brain can cause microglia secrete inflammatory factors such as TNF-α and IL-1β is emerging as the body’s immune response. The factors that can trigger microglia to secrete iNOS (Inducible Nitric Oxide Synthase) in order to protect the brain from attacking bacteria. iNOS is shown to have an important role in tuberculosis infection in the brain. TNF-α is a pro-inflammatory cytokine which is mostly produced by macrophages/microglia through several mechanisms. Therefore, to investigate how the expression of TNF-α and iNOS in the brain tissue of the mice is not infected with tuberculosis, tuberculosis infection with an incubation period of 8 weeks and 16 weeks. This study is a semiquantitative study by comparing the amount of expression of TNF-α and iNOS and all three groups of samples with treatment as has been mentioned. The expressions observation of TNF-α and iNOS in brain cell tissue of mice was conducted using immunohistochemical staining, and was seen in a microscope with a magnification of ×100. Brain cells that express TNF-α and iNOS are brown core, cytoplasm and cell walls. The results were obtained by the longer exposure to infection of the higher expression of TNF-α (r > 0688) and the expression of iNOS decreased (–0.993).

Essential and toxic metals in serum of individuals with active pulmonary tuberculosis in an endemic region

Trace elements play an important role in tuberculosis infection because their deficiencies can be associated with impaired immunity. Blood samples were collected from a total of 320 active pulmonary tuberculosis patients and healthy individuals. The serum concentrations of Zinc, Iron, Copper, Calcium, lead, Arsenic and Selenium were analyzed by atomic absorption spectrometry. The levels of trace elements were measured after 2, 4 and 6 months of anti-TB treatment initiation in TB infected groups. Compared to the control group, the concentrations of Zinc, Selenium, and Iron were significantly lower (P< 0.001) in tuberculosis patients; however, that of Arsenic, Lead, and copper was significantly higher (P< 0.001) in the serum of patients. Cu/Zn and Cu/Se ratios were also significantly higher (P< 0.001) in TB patients compared to the control group. In addition, serum concentration calcium was similar in both TB patients and healthy controls. Our results indicated that trace elements concentrations in tuberculosis patients are related to each element role in immune system. Wherever the element is essential for the pathogenesis of bacteria, its concentration will remain low; and contrariwise, when the element is toxic for the bacteria, its level will be regulated up to provide a perfect condition for bacterial growth.

Immunological Interactions of Tuberculosis with Drugs and Substance Use: A Systematic Review and Update

Background: Illicit drug and substance use exacerbates tuberculosis (TB) pandemic and complicates management of the disease. Cytokines play a crucial role in TB infection, and recreational drugs of abuse present a confounder in the understanding of immunology of TB. Therefore, this review presents an updated summary describing the immunological link between illicit drug use and TB. Methods: Information was obtained from previous research findings via Medline search (1990-2015) using the headings tuberculosis, drug interactions, cytokine alterations, prevalence of TB and illicit drug use. In addition, Google scholarly articles and PubMed citations were included in our search. Discussion: Recreational drug induced immunosuppression hastens TB progression among habitual substance users. Additionally, substance consumption in the context of TB infection alters cytokine production and the ensuing immune responses. In this regard, understanding these interactions forms an integral component in improving clinical outcomes among this cohort. Conclusions: Drug and substance abuse aggravates TB pandemic and remains a hindrance to effective TB diagnostic and therapeutic strategies. As such, poor adherence to TB treatment and interactions with drugs of abuse remain a hallmark for drug resistance that poses a unique setback in the fight against the world epidemic. In addition, substance consumption promotes derangement in inflammatory responses implicated in TB immunopathogenesis. This review necessitates clear identification on contribution of each substance towards TB predisposition and cytokine dysregulation while adjusting for confounders.

A Multi-Compartment Hybrid Computational Model Predicts Key Roles for Dendritic Cells in Tuberculosis Infection.

Tuberculosis (TB) is a world-wide health problem with approximately 2 billion people infected with Mycobacterium tuberculosis (Mtb, the causative bacterium of TB). The pathologic hallmark of Mtb infection in humans and Non-Human Primates (NHPs) is the formation of spherical structures, primarily in lungs, called granulomas. Infection occurs after inhalation of bacteria into lungs, where resident antigen-presenting cells (APCs), take up bacteria and initiate the immune response to Mtb infection. APCs traffic from the site of infection (lung) to lung-draining lymph nodes (LNs) where they prime T cells to recognize Mtb. These T cells, circulating back through blood, migrate back to lungs to perform their immune effector functions. We have previously developed a hybrid agent-based model (ABM, labeled GranSim) describing in silico immune cell, bacterial (Mtb) and molecular behaviors during tuberculosis infection and recently linked that model to operate across three physiological compartments: lung (infection site where granulomas form), lung draining lymph node (LN, site of generation of adaptive immunity) and blood (a measurable compartment). Granuloma formation and function is captured by a spatio-temporal model (i.e., ABM), while LN and blood compartments represent temporal dynamics of the whole body in response to infection and are captured with ordinary differential equations (ODEs). In order to have a more mechanistic representation of APC trafficking from the lung to the lymph node, and to better capture antigen presentation in a draining LN, this current study incorporates the role of dendritic cells (DCs) in a computational fashion into GranSim.ResultsThe model was calibrated using experimental data from the lungs and blood of NHPs. The addition of DCs allowed us to investigate in greater detail mechanisms of recruitment, trafficking and antigen presentation and their role in tuberculosis infection.ConclusionThe main conclusion of this study is that early events after Mtb infection are critical to establishing a timely and effective response. Manipulating CD8+ and CD4+ T cell proliferation rates, as well as DC migration early on during infection can determine the difference between bacterial clearance vs. uncontrolled bacterial growth and dissemination.

IL-37 Expression is Upregulated in Patients with Tuberculosis and Induces Macrophages Towards an M2-like Phenotype.

Interleukin-37 (IL-37), a member of the IL-1 family, primarily functions as an anti-inflammatory cytokine, reducing inflammation and suppressing the immune response. However, the expression and role of IL-37 in tuberculosis (TB) remains unknown. We aimed to measure serum levels of IL-37 and several important cytokines in 25 patients with active TB and to analyse their association with disease activity. We found that IL-37 levels decreased in patients with TB and recovered after treatment. IL-37 levels negatively correlated with the serum concentration of IFN-γ and IL-12 but positively correlated with IL-10 and TGF-β levels. After IL-37, secretion was blocked in peripheral blood mononuclear cells from active patients with TB, IFN-γ and IL-10 production was significantly upregulated; this was not observed in healthy donors or patients after treatment. IL-37 knockdown significantly enhanced the phagocytic activity of THP1-derived macrophages towards Mycobacterium tuberculosis (M. tb). M1/M2 polarization-associated markers were detected simultaneously, and IL-37 induced a phenotypic shift in THP1-derived macrophages towards a high CD206(+) and low CD86(+) macrophage subtype. Furthermore, this phenotypic shift was accompanied by upregulated mRNA levels of arginase 1, TGF-β and IL-10, which are characteristic hallmarks of M2 macrophages. In conclusion, our results suggest that increased levels of IL-37 in patients with TB are associated with IFN-γ, IL-12, IL-10 and TGF-β levels and that IL-37 plays a pathological role in TB infection by inhibiting the production of pro-inflammatory cytokines and inducing macrophages towards an M2-like phenotype. Thus, IL-37 may be a novel research target to understand the pathogenesis of TB infection.

A Genome Wide Association Scan of Bovine Tuberculosis Susceptibility in Holstein-Friesian Dairy Cattle

BackgroundBovine tuberculosis is a significant veterinary and financial problem in many parts of the world. Although many factors influence infection and progression of the disease, there is a host genetic component and dissection of this may enlighten on the wider biology of host response to tuberculosis. However, a binary phenotype of presence/absence of infection presents a noisy signal for genomewide association study.Methodology/Principal FindingsWe calculated a composite phenotype of genetic merit for TB susceptibility based on disease incidence in daughters of elite sires used for artificial insemination in the Irish dairy herd. This robust measure was compared with 44,426 SNP genotypes in the most informative 307 subjects in a genome wide association analysis. Three SNPs in a 65 kb genomic region on BTA 22 were associated (i.e. p<10−5, peaking at position 59588069, p = 4.02×10−6) with tuberculosis susceptibility.Conclusions/SignificanceA genomic region on BTA 22 was suggestively associated with tuberculosis susceptibility; it contains the taurine transporter gene SLC6A6, or TauT, which is known to function in the immune system but has not previously been investigated for its role in tuberculosis infection.

INVESTIGATION OF T CELL RECEPTORS IN THE PERIPHERAL BLOOD OF PATIENTS WITH ACTIVE PULMONARY TUBERCULOSIS

T cells have the capability of recognizing target cells through their T cell receptors (TCRs). Thus, the percentages of CD3+/ gamma–delta (γδ) TCR+and CD3+/ alpha–beta (αβ) TCR+T lymphocytes were investigated in active and inactive pulmonary tuberculosis (PT) patients and in healthy individuals. CD3+and CD3+/αβTCR+cell percentages were significantly lower in all PT patients than in healthy subjects. Percentages of CD3+/γδand CD3+/αβTCR+were not statistically different between active and inactive PT patients. It was concluded that αβTCR+T cells might have a protective role in tuberculosis infection.

Association of NRAMP 1 Gene Polymorphism with Susceptibility to Tuberculosis in Taiwanese Aboriginals

The human homologue of mice natural-resistance-associated macrophage protein 1 (Nramp 1) gene, NRAMP 1, has been reported to play a role in susceptibility to tuberculosis in humans. The aboriginal population in Taiwan has a five-fold higher prevalence of tuberculosis than people of Han ethnicity. Whether genetic factors such as NRAMP 1 polymorphism play a role in the prevalence of tuberculosis in Taiwanese aboriginals should be clarified. NRAMP 1 polymorphism was studied using a case-control design of patients with tuberculosis, including subjects of Han (Hans) and aboriginal ethnicity in Hualien, eastern Taiwan. The polymorphisms of NRAMP 1 at loci INT4, D543N, 77-385C/T, 3-UTR (CAAA) deletion and 5-(CA)n microsatellite markers were assessed by polymerase chain reaction on tissue DNA isolated from 105 aborigines and 110 Hans with tuberculosis. Comparable numbers of ethnically-matched controls were studied simultaneously. Two NRAMP 1 polymorphisms, INT4 and 5-(CA)n, were significantly associated with susceptibility to tuberculosis in aboriginals (p = 0.0070 and p = 0.0031, respectively). However, no association was detected at the five loci of NRAMP 1 polymorphisms among Hans (p > 0.08). Genetic variation in NRAMP 1 may affect susceptibility to and increase risk for tuberculosis in Taiwanese aboriginals. Although environmental factors play an important role in tuberculosis infection, genetic factors such as NRAMP 1 polymorphism may also contribute to the high prevalence of tuberculosis in Taiwanese aboriginals.

Corticosteroids in tuberculosis.

To examine the effects of corticosteroids used for concomitant disease states in patients with latent or active tuberculosis (TB). The role of corticosteroids in the treatment of extrapulmonary TB is also discussed. A MEDLINE search was conducted for the years 1953-1995. The International Pharmaceutical Abstracts service was also used to conduct an extensive literature review. In addition, relevant articles were cross-referenced to screen for additional information. During the literature review, emphasis was placed on human studies and individual case reports. The resurgence of TB in this decade has affected many populations, especially immunocompromised patients. These patients may need corticosteroid therapy for various concomitant diseases that might predispose a patient to develop primary TB infection or reactivate latent TB infection. In appropriate patients, prophylaxis with isoniazid is recommended. Corticosteroid therapy may benefit patients with some forms of extrapulmonary TB. After steroid therapy, improved survival and more rapid reduction of tuberculous symptoms have been noted in cases of tuberculous pleurisy, endobronchial TB, tuberculous meningitis, and tuberculous pericarditis. Corticosteroids may also be useful in controlling both fever and hypersensitivity reactions in pulmonary and extrapulmonary TB, although not routinely used for this purpose. Corticosteroids may play an important role in TB infection by promoting reactivation of latent infection. Corticosteroids may modify symptoms of some forms of extrapulmonary TB, although randomized, placebo-controlled studies are needed before corticosteroids will have a definitive place in the standard therapy of TB.