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https://www.readbyqxmd.com/read/28331797/paradoxical-response-with-increased-tumor-necrosis-factor-%C3%AE-levels-to-anti-tuberculosis-treatment-in-a-patient-with-disseminated-tuberculosis
#1
Sho Watanabe, Yugo Kaneko, Hironori Kawamoto, Tomoki Maehara, Yuri Baba, Ikumi Fujisaki, Nayuta Saito, Kai Ryu, Aya Seki, Tsugumi Horikiri, Akira Kinoshita, Hiroshi Takeda, Keisuke Saito, Kazuyosi Kuwano
It has been reported that tuberculosis (TB) worsens after cessation of tumor necrosis factor-α inhibitors and starting anti-TB treatment. Little is known about the immunological pathogenesis of this paradoxical response (PR). We report the first case of a TB patient in whom PR occurred concurrently with elevation of circulating tumor necrosis factor-α (TNFα) levels. A 75-year-old woman, who had been treated with adalimumab for SAPHO syndrome, developed disseminated TB. Soon after administration of anti-TB treatment (isoniazid, rifampicin, pyrazinamide, and ethambutol), and after discontinuation of adalimumab, a PR occurred...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28318770/expression-of-cathepsin-s-in-bcg-converts-it-into-a-pro-apoptotic-and-highly-immunogenic-strain
#2
Alice Lau, Vijender Singh, Hafid Soualhine, Zakaria Hmama
BACKGROUND: BCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28306733/hypervirulent-mycobacterium-tuberculosis-strain-triggers-necrotic-lung-pathology-associated-with-enhanced-recruitment-of-neutrophils-in-resistant-c57bl-6-mice
#3
Fabrício M Almeida, Thatiana L B Ventura, Eduardo P Amaral, Simone C M Ribeiro, Sanderson D Calixto, Marcelle R Manhães, Andreza L Rezende, Giliane S Souzal, Igor S de Carvalho, Elisangela C Silva, Juliana Azevedo da Silva, Eulógio C Q Carvalho, Afranio L Kritski, Elena B Lasunskaia
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) that in most cases induces irreversible necrosis of lung tissue as a result of excessive inflammatory reactions. The murine model of TB in resistant C57BL/6 mice infected with reference Mtb strains is widely used in TB studies; however, these mice do not show a necrotic pathology, which restricts their use in studies of irreversible tissue damage. Recently, we demonstrated that necrotic lung lesions could be induced in the C57BL/6 mice by highly virulent Mtb strains belonging to the modern Beijing sublineage...
2017: PloS One
https://www.readbyqxmd.com/read/28293387/cfp10-mfc%C3%AE-2-as-a-novel-tuberculosis-vaccine-candidate-increases-immune-response-in-mouse
#4
Ali Asghar Baghani, Saman Soleimanpour, Hadi Farsiani, Arman Mosavat, Masoud Yousefi, Zahra Meshkat, Seyed Abdolrahim Rezaee, Saeid Amel Jamehdar, Mohammad Reza Akbari Eydgahi, Hamid Sadeghian, Kiarash Ghazvini
OBJECTIVES: Despite treatment with antibiotics and vaccination with BCG, tuberculosis (TB) is still considered as one of the most important public health problems in the world. Therefore, designing and producing a more effective vaccine against TB seems urgently. In this study, immunogenicity of a fusion protein which consisting or comprising CFP-10 from Mycobacterium tuberculosis and the Fc-domain of mouse IgG2a was evaluated as a novel subunit vaccine candidate against TB. MATERIALS AND METHODS: The genetic constructs were cloned in pPICZαA expression vector and recombinant vectors (pPICZαA-CFP-10: Fcγ2a and pPICZαA-CFP-10:His) were transformed into Pichia pastoris...
February 2017: Iranian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/28280495/myeloid-and-t-cell-derived-tnf-protects-against-central-nervous-system-tuberculosis
#5
Nai-Jen Hsu, Ngiambudulu M Francisco, Roanne Keeton, Nasiema Allie, Valérie F J Quesniaux, Bernhard Ryffel, Muazzam Jacobs
Tuberculosis of the central nervous system (CNS-TB) is a devastating complication of tuberculosis, and tumor necrosis factor (TNF) is crucial for innate immunity and controlling the infection. TNF is produced by many cell types upon activation, in particularly the myeloid and T cells during neuroinflammation. Here we used mice with TNF ablation targeted to myeloid and T cell (MT-TNF(-/-)) to assess the contribution of myeloid and T cell-derived TNF in immune responses during CNS-TB. These mice exhibited impaired innate immunity and high susceptibility to cerebral Mycobacterium tuberculosis infection, a similar phenotype to complete TNF-deficient mice...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28261567/mycobacterium-tuberculosis-peptidyl-prolyl-isomerases-are-immunogenic-alter-cytokine-profile-and-aid-in-intracellular-survival
#6
Saurabh Pandey, Deeksha Tripathi, Mohd Khubaib, Ashutosh Kumar, Javaid A Sheikh, Gaddam Sumanlatha, Nasreen Z Ehtesham, Seyed E Hasnain
Mycobacterium tuberculosis (M. tb) has two peptidyl-prolyl isomerases (Ppiases) PpiA and PpiB, popularly known as cyclophilin A and cyclophilin B. The role of cyclophilins in processes such as signaling, cell surface recognition, chaperoning, and heat shock response has been well-documented. We present evidence that M. tb Ppiases modulate the host immune response. ELISA results revealed significant presence of antibodies to M. tb Ppiases in patient sera as compared to sera from healthy individuals. Treatment of THP-1 cells with increasing concentrations of rPpiA, induced secretion of pro-inflammatory cytokines TNF-α and IL-6...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28259000/th17-treg-imbalance-and-increased-interleukin-21-are-associated-with-liver-injury-in-patients-with-chronic-severe-hepatitis-b
#7
Bin Liu, Wei Gao, Li Zhang, Jing Wang, Min Chen, Mingli Peng, Hong Ren, Peng Hu
BACKGROUND: Th17/Treg imbalance and the levels of related cytokines are essential in the pathogenesis of autoimmune and infectious diseases. The aim of the current study was to assess the Treg/Th17 balance and the levels of related cytokines associated with various degrees of liver injury in patients with chronic hepatitis B virus (HBV) infection. METHODS: The proportions of peripheral Th17, Treg and Th1 cells in 7 patients classified as asymptomatic hepatitis B virus carriers (AsCs), 38 patients with low or moderate grade chronic hepatitis B (CHB-LM), 20 patients with chronic severe hepatitis B (CSHB), and 10 healthy controls (HCs) were determined by flow cytometry...
March 1, 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/28258153/rationalized-design-of-a-mucosal-vaccine-protects-against-mycobacterium-tuberculosis-challenge-in-mice
#8
Mushtaq Ahmed, Hongmei Jiao, Racquel Domingo-Gonzalez, Shibali Das, Kristin L Griffiths, Javier Rangel-Moreno, Uma M Nagarajan, Shabaana A Khader
Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is a leading cause of global morbidity and mortality. The only licensed TB vaccine, Mycobacterium bovis bacillus Calmette-Guerin (BCG), has variable efficacy in protecting against pulmonary TB. Thus, the development of more effective TB vaccines is critical to control the TB epidemic. Specifically, vaccines delivered through the mucosal route are known to induce Th17 responses and provide superior protection against Mtb infection. However, already tested Th17-inducing mucosal adjuvants, such as heat-labile enterotoxins and cholera toxins, are not considered safe for use in humans...
March 3, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28250925/b-cells-with-a-fasl-expressing-regulatory-phenotype-are-induced-following-successful-anti-tuberculosis-treatment
#9
Ilana C van Rensburg, Léanie Kleynhans, Alana Keyser, Gerhard Walzl, Andre G Loxton
INTRODUCTION: Studies show that B-cells, in addition to producing antibodies and antigen-presentation, are able to produce cytokines as well. These include regulatory cytokines such as IL-10 by regulatory B-cells. Furthermore, a rare regulatory subset of B-cells have the potential to express FasL, which is a death-inducing ligand. This subset of B-cells have a positive role during autoimmune disease, but has not yet been studied during tuberculosis. These FasL-expressing B-cells are induced by bacterial LPS and CpG, thus we hypothesized that this phenotype might be induced during tuberculosis as well...
March 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28249842/tb-lymphadenitis-is-associated-with-enhanced-baseline-and-antigen-specific-induction-of-type-1-and-type-17-cytokines-and-reduced-il-1%C3%AE-and-il-18-at-the-site-of-infection
#10
Gokul Raj Kathamuthu, Kadar Moideen, Dhanaraj Baskaran, Vaithilingam V Banurekha, Dina Nair, Gomathi Sekar, Rathinam Sridhar, Bharathi Vidyajayanthi, Ganeshan Gajendraraj, Dinesh Kumar Parandhaman, Alena Srinivasan, Subash Babu
Tuberculous lymphadenitis (TBL) is characterized by an expansion of Th1 and Th17 cells with altered serum levels of pro-inflammatory cytokines. However, the cytokine profile at the site of infection i.e. the affected lymph nodes, has not been examined in detail. To estimate the baseline and mycobacterial antigen - stimulated cytokine concentrations of Type 1, Type 17 and other pro-inflammatory cytokines in TBL, we examined both the baseline and the antigen - specific concentrations of these cytokines in TBL (n = 14) before and after chemotherapy and compared them with pulmonary tuberculosis infection (PTB, n = 14)...
March 1, 2017: Clinical and Vaccine Immunology: CVI
https://www.readbyqxmd.com/read/28228760/perturbed-microrna-expression-by-mycobacterium-tuberculosis-promotes-macrophage-polarization-leading-to-pro-survival-foam-cell
#11
Pankaj Kumar Ahluwalia, Rajan Kumar Pandey, Prabodh Kumar Sehajpal, Vijay Kumar Prajapati
Tuberculosis (TB) is one of the prevalent causes of death worldwide, with 95% of these deaths occurring in developing countries, like India. The causative agent, Mycobacterium tuberculosis (MTb) has the tenacious ability to circumvent the host's immune system for its own advantage. Macrophages are one of the phagocytic cells that are central to immunity against MTb. These are highly plastic cells dependent on the milieu and can showcase M1/M2 polarization. M1 macrophages are bactericidal in action, but M2 macrophages are anti-inflammatory in their immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28225338/potential-biomarkers-associated-with-discrimination-between-latent-and-active-pulmonary-tuberculosis
#12
R Kamakia, S Kiazyk, J Waruk, A Meyers, J Ochanda, T B Ball, J Oyugi
SETTING: A third of the world's population has latent tuberculous infection (LTBI). Current TB diagnostics used in developing countries are ineffective and are unable to distinguish LTBI from active TB. Identifying biomarkers that could aid in the early detection of TB and in distinguishing TB states could be a major breakthrough in global TB control. OBJECTIVE: To identify potential immune biomarkers to distinguish active TB from LTBI. DESIGN: A cross-sectional study was conducted among 19 active TB patients, 8 TB-negative individuals (controls) and 16 LTBI non-human immunodeficiency virus infected individuals in Nairobi, Kenya...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28225337/multiple-cytokines-for-the-detection-of-mycobacterium-tuberculosis-infection-in-children-with-tuberculosis
#13
N Nausch, C Lundtoft, G Schulz, H Henckel, E Mayatepek, B Fleischer, F M Marx, M Jacobsen
SETTING: Interferon-gamma (IFN-γ) release assays (IGRAs) play an important role in the diagnosis of Mycobacterium tuberculosis infection. However, in children with tuberculosis (TB), some studies have shown increased frequencies of false-negative or indeterminate IGRA results. OBJECTIVE: To analyse the spectrum of different cytokines to improve the diagnostic accuracy of IGRAs in latent tuberculous infection (LTBI) and active TB. DESIGN: We performed multiplex cytokine expression analysis of QuantiFERON® Gold In-Tube supernatants in children with active TB (n = 21) and disease-free contacts with (n = 15) and without LTBI (n = 12), to determine the sensitivity and specificity of the modified tests...
March 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28223969/mycobacterium-tuberculosis-prolyl-oligopeptidase-induces-in-vitro-secretion-of-proinflammatory-cytokines-by-peritoneal-macrophages
#14
Brina Portugal, Flávia N Motta, Andre F Correa, Diego O Nolasco, Hugo de Almeida, Kelly G Magalhães, Ana L V Atta, Francisco D Vieira, Izabela M D Bastos, Jaime M Santana
Tuberculosis (TB) is a disease that leads to death over 1 million people per year worldwide and the biological mediators of this pathology are poorly established, preventing the implementation of effective therapies to improve outcomes in TB. Host-bacterium interaction is a key step to TB establishment and the proteases produced by these microorganisms seem to facilitate bacteria invasion, migration and host immune response evasion. We presented, for the first time, the identification, biochemical characterization, molecular dynamics (MDs) and immunomodulatory properties of a prolyl oligopeptidase (POP) from Mycobacterium tuberculosis (POPMt)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28216183/safety-and-immunogenicity-of-the-novel-h4-ic31-tuberculosis-vaccine-candidate-in-bcg-vaccinated-adults-two-phase-i-dose-escalation-trials
#15
Maria Norrby, Timo Vesikari, Lars Lindqvist, Markus Maeurer, Raija Ahmed, Shahnaz Mahdavifar, Sean Bennett, J Bruce McClain, Barbara M Shepherd, Daner Li, David A Hokey, Ingrid Kromann, Søren T Hoff, Peter Andersen, Adriëtte W de Visser, Simone A Joosten, Tom H M Ottenhoff, Jan Andersson, Susanna Brighenti
BACKGROUND: Novel vaccine strategies are required to provide protective immunity in tuberculosis (TB) and prevent development of active disease. We investigated the safety and immunogenicity of a novel TB vaccine candidate, H4:IC31 (AERAS-404) that is composed of a fusion protein of M. tuberculosis antigens Ag85B and TB10.4 combined with an IC31® adjuvant. METHODS: BCG-vaccinated healthy subjects were immunized with various antigen (5, 15, 50, 150μg) and adjuvant (0, 100, 500nmol) doses of the H4:IC31 vaccine (n=106) or placebo (n=18) in two randomized, double-blind, placebo-controlled phase I studies conducted in a low TB endemic setting in Sweden and Finland...
March 14, 2017: Vaccine
https://www.readbyqxmd.com/read/28215633/tlr-4-mirna-32-5p-fstl1-signaling-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages
#16
Zhi-Min Zhang, Ai-Rong Zhang, Min Xu, Jun Lou, Wei-Qiang Qiu
Macrophages play a pivotal role in host immune response against mycobacterial infection, which is tightly modulated by multiple factors, including microRNAs. The purpose of the present study was to investigate the biological function and potential mechanism of miR-32-5p in human macrophages during Mycobacterium tuberculosis (M.tb) infection. The results demonstrated that miR-32-5p was robustly enhanced in THP-1 and U937 cells in response to M.tb infection. TLR-4 signaling was required for upregulation of miR-32-5p induced by M...
March 15, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28193909/rv2299c-a-novel-dendritic-cell-activating-antigen-of-mycobacterium-tuberculosis-fused-esat-6-subunit-vaccine-confers-improved-and-durable-protection-against-the-hypervirulent-strain-hn878-in-mice
#17
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Seungwha Paik, Hye-Soo Park, Woo Sik Kim, Hongmin Kim, Seung Bin Cha, Chul Hee Choi, Sung Jae Shin, Hwa-Jung Kim
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178208/effector-mechanisms-of-neutrophils-within-the-innate-immune-system-in-response-to-mycobacterium-tuberculosis-infection
#18
REVIEW
Eric Warren, Garrett Teskey, Vishwanath Venketaraman
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function...
February 7, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28177354/dietary-supplementation-with-tributyrin-prevented-weaned-pigs-from-growth-retardation-and-lethal-infection-via-modulation-of-inflammatory-cytokines-production-ileal-expression-and-intestinal-acetate-fermentation
#19
Y Gu, Y Song, H Yin, S Lin, X Zhang, L Che, Y Lin, S Xu, B Feng, D Wu, Z Fang
Weanling pigs, with an underdeveloped intestine and immature immune system, are usually subjected to depressed feed intake, growth retardation, and postweaning diarrhea. The aim of this study was to determine 1) the growth response of weaned pigs to supplemental tributyrin (TB) and 2) the potential effects and mechanisms of TB in modulating immune responses of lipopolysaccharide (LPS)-challenged piglets. A total of 240 piglets (Duroc × Large White × Landrace) were weaned at 21 d of age to a control (basal diet), supplemented with antibiotics (AB; +AB), supplemented with TB (+TB), or with supplemental AB and TB (+AB+TB) diets, with 10 replicate pens (6 piglets/pen) per diet...
January 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28167672/anthelmintic-therapy-modifies-the-systemic-and-mycobacterial-antigen-stimulated-cytokine-profile-in-helminth-latent-mycobacterium-tuberculosis-co-infection
#20
Rajamanickam Anuradha, Saravanan Munisankar, Yukthi Bhootra, Chandrakumar Dolla, Paul Kumaran, Thomas B Nutman, Subash Babu
Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) - antigen-stimulated levels of Type 1, Type 2, Type 17 and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis (Ss) infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent Ss infection have significantly lower levels of systemic and TB antigen-stimulated Type 1 (IFNγ, TNFα and IL-2) and Type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated Type 2 (IL-4 and IL-5) and regulatory (TGFβ) cytokines...
February 6, 2017: Infection and Immunity
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