Immune Response In Tuberculosis Research Articles

A regulatory variant in the C1Q gene cluster is associated with tuberculosis susceptibility and C1qA plasma levels in a South African population

Several genetic studies have implicated genes that encode for components of the innate immune response in tuberculosis (TB) susceptibility. The complement system is an early player in the innate immune response and provides the host with initial protection by promoting phagocytosis of apoptotic or necrotic cells. The C1q molecule is the first component of the classical pathway that leads to the activation of complement by binding to immune complexes and is encoded by the C1Q gene cluster. We investigated variants in this region to determine its association with TB susceptibility. Five single nucleotide polymorphisms (SNPs) (rs12033074, rs631090, rs172378, rs587585, and rs665691) were genotyped using TaqMan® SNP assays in 456 TB cases and 448 healthy controls and analysed by logistic regression models. The rs587585 variant showed a significant additive allelic association where the minor G allele was found more frequently in TB cases than in controls in both the discovery (p = 0.023; OR = 1.30; 95% CI, 1.04-1.64) and validation cohort (p = 0.038; OR = 1.31; 95% CI, 1.22-1.40). In addition, we detected increased C1qA expression when comparing cases and controls (p = 0.037) and linked this to a dosage effect of the G allele, which increased C1qA expression in TB cases. This is the first study to report the association of C1Q gene polymorphisms with progression to tuberculosis.

Analyzing the Mycobacterium tuberculosis immune response by T-cell receptor clustering with GLIPH2 and genome-wide antigen screening.

CD4+ T cells are critical to fighting pathogens, but a comprehensive analysis of human T cell specificities is hindered by the diversity of HLA alleles (>20,000) and the complexity of many pathogen genomes. We previously described GLIPH, an algorithm to cluster T cell receptors (TCRs) that recognize the same epitope and to predict their HLA restriction, but this method loses efficiency and accuracy when analyzing >10,000 TCRs. Here we describe an improved algorithm, GLIPH2, that can process millions of TCR sequences. We used GLIPH2 to analyze 19,044 unique TCRβsequences from 58 individuals latently infected with Mycobacterium tuberculosis (Mtb) and to group them according to their specificity. To identify the epitopes targeted by clusters of Mtb-specific T cells, we carried out a screen of 3,724 distinct proteins covering 95% of Mtb protein-coding genes using artificial antigen presenting cells (aAPC) and reporter T cells. We found that at least five PPE (Pro-Pro-Glu) proteins are targets for T cell recognition in Mtb.

Deficiency in the glycosyltransferase Gcnt1 increases susceptibility to tuberculosis through a mechanism involving neutrophils

Modulation of immunity and disease by glycans is increasingly recognized. However, how host glycosylation shapes and is shaped by tuberculosis remains poorly understood. We show that deficiency in the glucosaminyl (N-acetyl) transferase 1 (Gcnt1), a key enzyme for core-2 O-glycans biosynthesis, drives susceptibility to Mycobacterium tuberculosis infection. The increased susceptibility of Gcnt1 deficient mice was characterized by extensive lung immune pathology, mechanistically related to neutrophils. Uninfected Gcnt1 deficient mice presented bone marrow, blood and lung neutrophilia, which further increased with infection. Blood neutrophilia required Gcnt1 deficiency in the hematopoietic compartment, relating with enhanced granulopoiesis, but normal cellular egress from the bone marrow. Interestingly, for the blood neutrophilia to translate into susceptibility to M. tuberculosis infection, Gnct1 deficiency in the stroma was also necessary. Complete Gcnt1 deficiency associated with increased lung expression of the neutrophil chemoattractant CXCL2. Lastly, we demonstrate that the transcript levels of various glycosyltransferase-encoding genes were altered in whole blood of active tuberculosis patients and that sialyl Lewis x, a glycan widely present in human neutrophils, was detected in the lung of tuberculosis patients. Our findings reveal a previously unappreciated link between Gcnt1, neutrophilia and susceptibility to M. tuberculosis infection, uncovering new players balancing the immune response in tuberculosis.

Anti-PD-1 immunotherapy leads to tuberculosis reactivation via dysregulation of TNF-α.

Previously, we developed a 3-dimensional cell culture model of human tuberculosis (TB) and demonstrated its potential to interrogate the host-pathogen interaction (Tezera et al., 2017a). Here, we use the model to investigate mechanisms whereby immune checkpoint therapy for cancer paradoxically activates TB infection. In patients, PD-1 is expressed in Mycobacterium tuberculosis (Mtb)-infected lung tissue but is absent in areas of immunopathology. In the microsphere model, PD-1 ligands are up-regulated by infection, and the PD-1/PD-L1 axis is further induced by hypoxia. Inhibition of PD-1 signalling increases Mtb growth, and augments cytokine secretion. TNF-α is responsible for accelerated Mtb growth, and TNF-α neutralisation reverses augmented Mtb growth caused by anti-PD-1 treatment. In human TB, pulmonary TNF-α immunoreactivity is increased and circulating PD-1 expression negatively correlates with sputum TNF-α concentrations. Together, our findings demonstrate that PD-1 regulates the immune response in TB, and inhibition of PD-1 accelerates Mtb growth via excessive TNF-α secretion.

Reconsidering the Optimal Immune Response to Mycobacterium tuberculosis.

Tuberculosis is unfortunately once again killing more people than any other infection. Despite global biomedical and public health efforts, standard interventions to control the pandemic have not advanced in most resource-poor settings, in contrast to other global diseases such as malaria and HIV infection. The authors propose that reconsidering concepts of the optimal host immune response to Mycobacterium tuberculosis is required to develop a paradigm that will inform novel interventions. The development of active tuberculosis associated with cancer treatment by immune checkpoint inhibition highlights that merely driving a stronger immune response may not improve control of the pathogen. Here, we present different models of the host-pathogen interaction that are consistent with the complexity of human infection. We consider both the protective and harmful components of the immune response in tuberculosis and develop a multiparameter framework that predicts disease risk. This novel conceptual model is important to inform emerging interventions to improve outcomes in tuberculosis by defining the ideal host response to target.

Role of CD8 T-cell in immune response to tuberculosis-specific antigen in QuantiFERON-TB Gold Plus

Recent contacts with active TB (tuberculosis) patients were screened for latent tuberculosis infection (LTBI) because of their greater relative risk for developing active TB. QuantiFERON®-TB Gold Plus (QFT-Plus) offers two TB-specific antigen tubes (TB1 and TB2). TB1 elicits CD4 T-cell responses, and TB2 is designed to elicit both CD4 and CD8 T-cell responses. These mechanisms could be useful for estimating the role of CD8 T-cell immune responses to TB-specific antigens. To estimate the QFT-Plus capability to diagnose LTBI, a prospective cross-sectional study was conducted. A total of 412 TB contacts (median age 44 years) were enrolled. The positivity rates of QFT-Plus, TB1 and TB2 were 7.5%, 6.3% and 7.2%, respectively. TB2 showed a higher positivity rate compared to TB1, but without significant difference. The interferon (IFN)-γ productions of TB1 and TB2 were well correlated (r = 0.934, P < 0.001). The ratio of IFN-γ production between TB1 and TB2 showed a median (interquartile range) of IFN-γ[QFT-Plus TB2]/IFN-γ[QFT-Plus TB1] of 1.09 (0.91–1.36). CD8 T-cell immune response to TB-specific antigens varied among subjects. CD8 T-cell potentially boosts IFN-γ productions in QFT-Plus and results in the detection of more persons with LTBI. However, there was no significant difference in the positivity rates of QFT-Plus TB1 and TB2 in our TB contact investigation. The contribution of CD8 T-cells might be small for the diagnosis of LTBI. The analysis of IFN-γ production in both TB1 and TB2 would lead to further analysis of the TB immune response, and especially that caused by CD8 T-cells.

Diagnostic value of miR-145 and its regulatory role in macrophage immune response in tuberculosis.

Tuberculosis (TB) induced by Mycobacterium tuberculosis (Mtb) is a serious global health burden. This study sought to investigate the expression and diagnostic value of serum miR-145 in TB patients and explore the biological function of miR-145 using macrophages. Serum expression levels of miR-145 were estimated by quantitative real-time PCR. A receiver operating characteristic curve was plotted to evaluate the diagnostic accuracy of miR-145. This study further focused on the effects of miR-145 on cell viability and inflammation in macrophages upon Mtb infection, and explored the potential target gene of miR-145. Serum expression levels of miR-145 were decreased in TB patients, and the upregulated inflammatory cytokines in TB patients were negatively correlated with the serum expression levels of miR-145. miR-145 had considerable diagnostic accuracy in distinguishing of TB patients from healthy individuals and differentiating between active TB cases and latent TB cases. Mtb infection induced an increase in cell viability and inflammatory responses in macrophages, but these promoting effects were rescued by the overexpression of miR-145. CXCL16 was determined as a target gene of miR-145 in macrophages. Overall, this study demonstrated that the decreased serum miR-145 expression serves a candidate diagnostic biomarker in TB patients. The overexpression of miR-145 in macrophages upon Mtb infection can suppress cell viability and infection-induced inflammation via regulating CXCL16, indicating the potential of miR-145 as a therapeutic target of TB.

Assessment of vitamin status in patients with nontuberculous mycobacterial pulmonary disease: Potential role of vitamin A as a risk factor

As microbiological diagnostic techniques improve and the frequency of nontuberculous mycobacterial pulmonary disease (NTM-PD) infection increases worldwide, NTM-PD is becoming increasingly important to clinicians and researchers. Vitamin activity has been associated with the host immune response in tuberculosis; however, such information is very limited in NTM-PD. We performed a case-control study in 150 patients with NTM-PD and 150 healthy controls to investigate serum vitamin status. We measured concentrations of vitamins A, D, and E along with homocysteine and methylmalonic acid (MMA) as indicators of vitamin B12 deficiency, using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. The serum concentrations of vitamins A and E were significantly lower in patients with NTM-PD than in healthy controls (1.5 vs. 2.1 µmol/L, p < 0.01 for vitamin A; and 27.3 vs. 33.1 µmol/L, p < 0.01 for vitamin E). In contrast, the serum concentrations of vitamin D and homocysteine were not significantly different between the two groups. Vitamin A deficiency (< 1.05 µmol/L) was significantly more prevalent in patients with NTM-PD than in healthy controls (p < 0.01) and was associated with an 11-fold increase in risk of NTM-PD. Multiple vitamin deficiencies were only observed in patients with NTM-PD (7.3% of all NTM-PD patients). Positive correlations were observed among vitamins (vitamins A and D; r = 0.200, p < 0.05; vitamins D and E, r = 0.238, p < 0.05; vitamins A and E, r = 0.352, p < 0.05). Serum vitamin status, demographic variables, and biochemical indicators were not associated with treatment outcomes. Vitamin A deficiency was strongly associated with patients with NTM-PD. Our study suggests that altered vitamin status is associated with mycobacterial disease. Future well-designed prospective studies with large patient cohorts addressing these issues are needed to clarify the significance of vitamins in NTM-PD.

Lung Tissue Resident Memory T-Cells in the Immune Response to Mycobacterium tuberculosis.

Despite widespread BCG vaccination and effective anti-TB drugs, Tuberculosis (TB) remains the leading cause of death from an infectious agent worldwide. Several recent publications give reasons to be optimistic about the possibility of a more effective vaccine, but the only full-scale clinical trial conducted failed to show protection above BCG. The immunogenicity of vaccines in humans is primarily evaluated by the systemic immune responses they generate, despite the fact that a correlation between these responses and protection from TB disease has not been demonstrated. A novel approach to tackling this problem is to study the local immune responses that occur at the site of TB infection in the human lung, rather than those detectable in blood. There is a growing understanding that pathogen specific T-cell immunity can be highly localized at the site of infection, due to the existence of tissue resident memory T-cells (Trm). Notably, these cells do not recirculate in the blood and thus may not be represented in studies of the systemic immune response. Here, we review the potential role of Trms as a component of the TB immune response and discuss how a better understanding of this response could be harnessed to improve TB vaccine efficacy.

Identification and characterization of lung commensal bacteria that modulate immune response in Tuberculosis

Abstract Tuberculosis (TB) is still one of the deadliest infectious diseases in humans. As TB disease is driven by exacerbation of the immune response, promising approaches include host-targeting therapies aiming at controlling the balance between pathogen eradication and limitation of the inflammation in order to prevent immunopathology. Such immune modulation has been observed through modification of the gut-microbiota compartment with oral administration of specific bacterial strains (i.e. probiotics) in other respiratory diseases. In TB, a dysbiosis of the microbiota is observed in patients, and microbiota perturbation in mice increases susceptibility to Mycobacterium tuberculosis (Mtb). Here, we assessed whether bacterial strains isolated from the recently described lung microbiota could have a local impact on Mtb infection by protecting against immune dysfunction for the host benefit. Through intranasal administration in mice, we identified different microbiota strains isolated from mouse lungs with a strong ability to modulate the lung T cell compartment. The same in vivo approach in Mtb-infected mice revealed one strain with a remarkable capacity to diminish Mtb infection-associated lung immunopathology, accompanied by a specific immune signature characterized by an increase level of regulatory T cells sharing surprisingly T-helper 17 cell markers. Collectively, this work may contribute to the design of host-directed therapies to reduce the destructive inflammatory response in TB, without further fomenting the occurrence of multiple-drug resistant Mtb strains. It will also shed light on poorly described populations in the lungs such as the RORgt+ Foxp3+ biTregs and their interactions with the microbiota.

Dynamics of Mycobacterium tuberculosis Ag85B Revealed by a Sensitive Enzyme-Linked Immunosorbent Assay.

Secretion of specific proteins contributes to pathogenesis and immune responses in tuberculosis and other bacterial infections, yet the kinetics of protein secretion and fate of secreted proteins in vivo are poorly understood. We generated new monoclonal antibodies that recognize the Mycobacteriumtuberculosis secreted protein Ag85B and used them to establish and characterize a sensitive enzyme-linked immunosorbent assay (ELISA) to quantitate Ag85B in samples generated in vitro and in vivo We found that nutritional or culture conditions had little impact on the secretion of Ag85B and that there is considerable variation in Ag85B secretion by distinct strains in the M. tuberculosis complex: compared with the commonly used H37Rv strain (lineage 4), Mycobacteriumafricanum (lineage 6) secretes less Ag85B, and two strains from lineage 2 secrete more Ag85B. We also used the ELISA to determine that the rate of secretion of Ag85B is 10- to 100-fold lower than that of proteins secreted by Gram-negative and Gram-positive bacteria, respectively. ELISA quantitation of Ag85B in lung homogenates of M. tuberculosis H37Rv-infected mice revealed that although Ag85B accumulates in the lungs as the bacterial population expands, the amount of Ag85B per bacterium decreases nearly 10,000-fold at later stages of infection, coincident with the development of T cell responses and arrest of bacterial population growth. These results indicate that bacterial protein secretion in vivo is dynamic and regulated, and quantitation of secreted bacterial proteins can contribute to the understanding of pathogenesis and immunity in tuberculosis and other infections.IMPORTANCE Bacterial protein secretion contributes to host-pathogen interactions, yet the process and consequences of bacterial protein secretion during infection are poorly understood. We developed a sensitive ELISA to quantitate a protein (termed Ag85B) secreted by M. tuberculosis and used it to find that Ag85B secretion occurs with slower kinetics than for proteins secreted by Gram-positive and Gram-negative bacteria and that accumulation of Ag85B in the lungs is markedly regulated as a function of the bacterial population density. Our results demonstrate that quantitation of bacterial proteins during infection can reveal novel insights into host-pathogen interactions.

Assessment of Vitamin Status in Patients with Nontuberculous Mycobacterial Pulmonary Disease: Potential Role of Vitamin A as a Risk Factor.

As microbiological diagnostic techniques improve and the frequency of nontuberculous mycobacterial pulmonary disease (NTM-PD) infection increases worldwide, NTM-PD is becoming increasingly important to clinicians and researchers. Vitamin activity has been associated with the host immune response in tuberculosis; however, such information is very limited in NTM-PD. We performed a case-control study in 150 patients with NTM-PD and 150 healthy controls to investigate serum vitamin status. We measured concentrations of vitamins A, D, and E along with homocysteine and methylmalonic acid (MMA) as indicators of vitamin B12 deficiency, using high-performance liquid chromatography (HPLC) or HPLC-tandem mass spectrometry. The serum concentrations of vitamins A and E were significantly lower in patients with NTM-PD than in healthy controls (1.5 vs. 2.1 µmol/L, p < 0.01 for vitamin A; and 27.3 vs. 33.1 µmol/L, p < 0.01 for vitamin E). In contrast, the serum concentrations of vitamin D and homocysteine were not significantly different between the two groups. Vitamin A deficiency (< 1.05 µmol/L) was significantly more prevalent in patients with NTM-PD than in healthy controls (p < 0.01) and was associated with an 11-fold increase in risk of NTM-PD. Multiple vitamin deficiencies were only observed in patients with NTM-PD (7.3% of all NTM-PD patients). Positive correlations were observed among vitamins (vitamins A and D; r = 0.200, p < 0.05; vitamins D and E, r = 0.238, p < 0.05; vitamins A and E, r = 0.352, p < 0.05). Serum vitamin status, demographic variables, and biochemical indicators were not associated with treatment outcomes. Vitamin A deficiency was strongly associated with patients with NTM-PD. Our study suggests that altered vitamin status is associated with mycobacterial disease. Future well-designed prospective studies with large patient cohorts addressing these issues are needed to clarify the significance of vitamins in NTM-PD.

The Effectiveness of Spiritual Emotional Breathing Towards Respiratory Function and Immune Response of Tuberculosis Patients

Introduction: Tuberculosis is one cause of infectious death worldwide. In relation to the healing of pulmonary tuberculosis in Indonesia, there are still certain areas where the cure rate is still low. This study aims to identify the effect of spiritual emotional breathing (SEB) on the quality of respiratory function and the modulation of immune response in tuberculosis patients.Methods: The study used a quasi-experimental design with two groups of pre-post-test design. The population was 34 patients with tuberculosis in East Perak’s primary health care. The independent variable was SEB (spiritual emotional breathing). The dependent variables were peak expiratory flow rate (PEFR), pulse, oxygen saturation, breath frequency, breath sound, stiffness complaints, human IL-2, human cortisol, IgG.Results: The results showed that there was a significant difference in PEFR, pulse, oxygen saturation, respiratory rate, respiratory sound, stiffness, human IL-2, human cortisol, IgG.Conclusion: SEB can improve the quality of respiratory function and the modulation of immune response in tuberculosis patients. The emotional spiritual approach is part of the science of energy psychology that aims to turn the negative energy in a person into positive energy that can help the healing process. This therapy is performed as a complementary therapy for TB patients to improve their quality of life and the control of symptoms

The Troika Host-Pathogen-Extrinsic Factors in Tuberculosis: Modulating Inflammation and Clinical Outcomes.

The already enormous burden caused by tuberculosis (TB) will be further aggravated by the association of this disease with modern epidemics, as human immunodeficiency virus and diabetes. Furthermore, the increasingly aging population and the wider use of suppressive immune therapies hold the potential to enhance the incidence of TB. New preventive and therapeutic strategies based on recent advances on our understanding of TB are thus needed. In particular, understanding the intricate network of events modulating inflammation in TB will help to build more effective vaccines and host-directed therapies to stop TB. This review integrates the impact of host, pathogen, and extrinsic factors on inflammation and the almost scientifically unexplored complexity emerging from the interactions between these three factors. We highlight the exciting data showing a contribution of this troika for the clinical outcome of TB and the need of incorporating it when developing novel strategies to rewire the immune response in TB.

Insights on Blood Cytokines Production under Different &amp;lt;i&amp;gt;In Vitro&amp;lt;/i&amp;gt; Mycobacterial Antigens in Tuberculosis Intestinal Parasites Co Infected Patients

Background: The concomitant presence of intestinal parasite infections (IP) and tuberculosis (TB) has relevance. M. tuberculosis immune response is associated with type 1 T helper cell (Th1) while IP is associated with type Th2 cell. However, there are several contradictory reports on cytokine production under coinfection and this could be in association to the mycobacterial antigens used in the studies. Aim: To get insight into the effects of different M. tuberculosis-specific antigens (ESAT-6/CFP-10 and 38 kDa/CFP-10) in generating of appropriate cytokines on peripheral blood mononuclear cells of IPTB co infected patients. Method: ELISA assessed IFN-γ and other 16 cytokines production and plasm IgE. In 18 months, we documented demographic, economic, clinical characteristics and IP frequency in individuals from Brazil. Results: An overall 10/35 (28.5%) were IPTB co infected and 40/76 (52.6%; p = 0.024) asymptomatic intestinal parasite infected community controls (IPCC). Endo-limax nana (40%) and Entamoeba coli (22%), were the most nonpathogenic protozoan identified and Entamoeba histolytica, Giardia intestinalis, Ascaris lumbricoides and Strongyloides stercoralis were the pathogenic species (40%). IgE was higher in IPCC (p = 0.036). Cytokine profiles were significantly biased toward a Th2 type IL-5 (p = 0.001) and IL-13 (p = 0.033), pro-inflammatory GM-CSF (p = 0.019) and borderline lower IL-1β in IPTB, all associated with ESAT-6/CFP-10, while IL-7 was borderline lower, but 38 kDa/CFP-10 associated; as well as IL-8 higher (p < 0.049) vs CC/IPCC. The TB/IPTB IFN-γ levels were similar to both antigens stimuli (p ≥ 0.208). Conclusion: Therefore, coin-cident IPTB coinfection did not exert a significant inhibitory effect in IFN-γ production in response to either of the two antigens, but the partial discrepancy in Th1/Th2 response, is associated with the antigen priming cells.

Down-regulation of Notch signaling pathway reverses the Th1/Th2 imbalance in tuberculosis patients

Th1/Th2 imbalance to Th2 is of significance in the peripheral immune responses in Tuberculosis (TB) development. However, the mechanisms for Th1/Th2 imbalance are still not well determined. Notch signaling pathway is involved in the peripheral T cell activation and effector cell differentiation. However, whether it affects Th1/Th2 imbalance in TB patients is still not known. Here, we used γ-secretase inhibitor (DAPT) to treat the peripheral blood mononuclear cells (PBMCs) from healthy people or individuals with latent or active TB infection in vitro, respectively. Then, the Th1/Th2 ratios were determined by flow cytometry, and cytokines of IFN-γ, IL-4, IL-10 in the culture supernatant were measured by CBA method. The Notch signal pathway associated proteins Hes1, GATA3 and T-bet were quantitated by real-time PCR or immunoblotting. Our results showed that DAPT effectively inhibited the protein level of Hes1. In TB patients, the Th2 ratio increased in the PBMCs, alone with the high expression of GATA3 and IL-4, resulting in the high ratios of Th2/Th1 and GATA3/T-bet in TB patients. However, Th2 cells ratio decreased after blocking the Notch signaling pathway by DAPT and the Th2/Th1 ratio in TB patients were DAPT dose-dependent, accompanied by the decrease of IL-4 and GATA3. But, its influence on Th1 ratio and Th1 related T-bet and IFN-γ levels were not significant. In conclusion, our results suggest that blocking Notch signaling by DAPT could inhibit Th2 responses and restore Th1/Th2 imbalance in TB patients.

Malnutrition: Modulator of Immune Responses in Tuberculosis.

Nutrition plays a major role in the management of both acute and chronic diseases, in terms of body’s response to the pathogenic organism. An array of nutrients like macro- and micro-nutrients, vitamins, etc., are associated with boosting the host’s immune responses against intracellular pathogens including mycobacterium tuberculosis (M.tb). These nutrients have an immunomodulatory effects in controlling the infection and inflammation process and nutritional deficiency of any form, i.e., malnutrition may lead to nutritionally acquired immunodeficiency syndrome, which greatly increases an individual’s susceptibility to progression of infection to disease. This narrative review looks at the various mechanisms by which nutrition or its deficiency leads to impaired cell mediated and humoral immune responses, which in turn affects the ability of an individual to fight M.tb infection or disease. There is very little evidence in the literature that any specific food on its own or a specific quantity can alter the course of TB disease or be effective in the treatment of malnutrition. Further clinical trials or studies will be needed to recommend and to better understand the link between malnutrition, tuberculosis, and impaired immunity.

The expressions and roles of different forms of IL-22 in Mycobacterium tuberculosis infection

Despite evidence suggesting an anti-Mycobacterium tuberculosis effector function of CD4+ T cells that produce and retain IL-22 in macaques, the general role of IL-22 in tuberculosis infection is still poorly characterized. To explore the immune mechanism in the pathogenesis of tuberculosis in humans, here we evaluated different forms of IL-22 in populations with different tuberculosis infection statuses. We enrolled 156 subjects including 49 patients with pulmonary tuberculosis, 27 patients with tuberculous pleurisy (TPE), 38 individuals with latent tuberculous infection (LTBI) and 42 healthy controls (HC). We found significantly higher IL-22 levels at the tuberculosis infection site than in the peripheral blood as well as higher antigen-specific IL-22 levels in the culture supernatant for patients with active tuberculosis than in healthy controls. The proportions of IL-22 + CD4+ T and IL-22 + CD8+ T cells in patients with active tuberculosis were significantly higher than those in the latent tuberculosis infection group and the healthy control group, based on intracellular cytokine staining. However, surprisingly, we found membrane-bound IL-22+ T cells, including CD4+ T cells and CD8+ T cells, by surface staining, especially in patients with active tuberculosis. Furthermore, the expression of membrane-bound IL-22 significantly decreased after drug therapy. In conclusion, our results suggest that IL-22 has various roles in tuberculosis immune responses. In particular, membrane-bound IL-22+ T cells may play important roles in the human immune response to Mycobacterium.

Ex vivo mycobacterial growth inhibition assay- re-evaluation of the tool for tuberculosis immune response and vaccine efficacy

Abstract not available&#x0D; Bangladesh J Med Microbiol 2017; 11 (1): 1-2

HIV Interferes with Mycobacterium tuberculosis Antigen Presentation in Human Dendritic Cells

HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC)-mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB. Human immature DCs coinfected with HIV/Mtb had decreased expression of human leukocyte antigen antigen D related and the costimulatory molecules CD40, CD80, and CD86. In addition, Mtb-infected DCs triggered a significant release of the proinflammatory cytokines IL-6, IL-1β, and tumor necrosis factor-α, whereas coinfected DCs did not. To assess the DC antigen presentation capacity, we measured interferon-γ from co-cultures of DCs and autologous Mtb antigen-specific CD4+ T cells. Interferon-γ release was significantly reduced when purified protein derivative- and Ag85B-specific CD4+ T cells had been activated with coinfected DCs compared to Mtb-infected DCs, and this effect was attributed to Mtb antigen processing rather than peptide-major histocompatibility complex class II loading. Evaluating autophagy as a measure of vesicular processing and maturation further revealed that HIV efficiently blocks initiation of this pathway during coinfection. Overall, our results demonstrate that HIV impairs Mtb antigen presentation in DCs, thereby suppressing an important cell linking innate and adaptive immune response in TB.