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https://www.readbyqxmd.com/read/28440335/mycobacterium-tuberculosis-pe_pgrs41-enhances-the-intracellular-survival-of-m-smegmatis-within-macrophages-via-blocking-innate-immunity-and-inhibition-of-host-defense
#1
Wanyan Deng, Quanxin Long, Jie Zeng, Ping Li, Wenmin Yang, Xinchun Chen, Jianping Xie
The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#2
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28412202/the-immunosuppressive-effects-of-a-novel-recombinant-lipq-rv2485c-protein-of-mycobacterium-tuberculosis-on-human-macrophage-cell-lines
#3
Anjani Kumar, Manisha, Gurkamaljit Kaur Sangha, Anju Shrivastava, Jagdeep Kaur
Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28399967/type-1-polarised-dendritic-cells-are-a-potent-immunogen-against-mycobacterium-tuberculosis
#4
Y Satake, Y Nakamura, M Kono, H Hozumi, T Nagata, K Tsujimura, N Enomoto, T Fujisawa, N Inui, T Fujiyama, Y Tokura, T Matsui, K Yokomura, M Shirai, H Hayakawa, T Suda
OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response. METHODS: Monocyte-derived DCs from TB patients were induced to mature using a 'standard' cytokine cocktail (interleukin [IL] 1β, tumour necrosis factor alpha [TNF-α], IL-6 and prostaglandin E2) or a type 1-polarised DC (DC1) cocktail (IL-1β, TNF-α, interferon [IFN] α, IFN-γ and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6)...
May 1, 2017: International Journal of Tuberculosis and Lung Disease
https://www.readbyqxmd.com/read/28388655/functional-toll-like-receptor-tlr-2-polymorphisms-in-the-susceptibility-to-inflammatory-bowel-disease
#5
Helga Paula Török, Victor Bellon, Astrid Konrad, Martin Lacher, Laurian Tonenchi, Matthias Siebeck, Stephan Brand, Enrico Narciso De Toni
BACKGROUND: The recent genome-wide association studies (GWAS) in inflammatory bowel disease (IBD) suggest significant genetic overlap with complex mycobacterial diseases like tuberculosis or leprosy. TLR variants have previously been linked to susceptibility for mycobacterial diseases. Here we investigated the contribution to IBD risk of two TLR2 polymorphisms, the low-prevalence variant Arg753Gln and the GTn microsatellite repeat polymorphism in intron 2. We studied association with disease, possible correlations with phenotype and gene-gene interactions...
2017: PloS One
https://www.readbyqxmd.com/read/28374535/association-of-esat-6-cfp-10-induced-ifn-%C3%AE-tnf-%C3%AE-and-il-10-with-clinical-tuberculosis-evidence-from-cohorts-of-pulmonary-tuberculosis-patients-household-contacts-and-community-controls-in-an-endemic-setting
#6
F Abebe, M Belay, M Legesse, A Mihret, K S Franklin
Mycobacterium tuberculosis (Mtb) early secreted protein antigen 6 (ESAT-6) and culture filtrate protein 10 (CFP-10) are among candidate vaccines against tuberculosis (TB). Results of experimental animal models show that these antigens are associated with induction of strong T cell immunity (IFN-γ production), while others report that these proteins as virulent factors involved in pathogenicity of Mtb infection. However, the role of ESAT-6/CFP-10 during natural Mtb infections in humans has not been established...
April 3, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28359325/early-versus-late-bcg-vaccination-in-hiv-1-exposed-infants-in-uganda-study-protocol-for-a-randomized-controlled-trial
#7
Victoria Nankabirwa, James K Tumwine, Olive Namugga, Thorkild Tylleskär, Grace Ndeezi, Bjarne Robberstad, Mihai G Netea, Halvor Sommerfelt
BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccination may have nonspecific effects, i.e., effects on childhood morbidity and mortality that go beyond its effect on the risk of childhood tuberculosis (TB). Though the available scientific literature is mostly from observational studies, and is fraught with controversy, BCG vaccination at birth may protect infants in high-mortality populations against serious infections other than TB. Yet, other studies indicate that giving BCG later in infancy may modify immune responses to non-TB antigens and potentially enhance immunity, potentially also against tuberculosis (TB)...
March 31, 2017: Trials
https://www.readbyqxmd.com/read/28355218/scd163-levels-as-a-biomarker-of-disease-severity-in-leprosy-and-visceral-leishmaniasis
#8
Ricardo Luís Louzada Silva, Marcio B Santos, Priscila L S Almeida, Thayse S Barros, Lucas Magalhães, Rodrigo A Cazzaniga, Patrícia R M Souza, Nívea F Luz, Jaqueline França-Costa, Valeria M Borges, Djalma S Lima-Junior, Michael W Lipscomb, Malcolm S Duthie, Steven G Reed, Roque Pacheco Almeida, Amélia Ribeiro Jesus
BACKGROUND: CD163, receptor for the haptoglobin-hemoglobin complex, is expressed on monocytes/macrophages and neutrophils. A soluble form of CD163 (sCD163) has been associated with the M2 macrophage phenotype, and M2 macrophages have been shown to down-modulate inflammatory responses. In particular, previous studies have shown that M2 is closely associated with the most severe clinical presentation of leprosy (i.e. lepromatous leprosy (LL)), as well as tuberculosis. We hypothesized that sCD163 correlates with severity of diseases caused by intracellular pathogens...
March 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28337427/comparative-proteomics-analysis-of-human-macrophages-infected-with-virulent-mycobacterium-bovis
#9
Pei Li, Rui Wang, Wenqi Dong, Linlin Hu, Bingbing Zong, Yanyan Zhang, Xiangru Wang, Aizhen Guo, Anding Zhang, Yaozu Xiang, Huanchun Chen, Chen Tan
Mycobacterium bovis (M. bovis), the most common pathogens of tuberculosis (TB), is virulent to human and cattle, and transmission between cattle and humans warrants reconsideration concerning food safety and public health. Recently, efforts have begun to analyze cellular proteomic responses induced by Mycobacterium tuberculosis (M. tb). However, the underlying mechanisms by which virulent M. bovis affects human hosts are not fully understood. For the present study, we utilized a global and comparative labeling strategy of isobaric tag for relative and absolute quantitation (iTRAQ) to assess proteomic changes in the human monocyte cell line (THP-1) using a vaccine strain and two virulent strains H37Rv and M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28336735/risk-of-tuberculosis-in-patients-treated-with-tnf-%C3%AE-antagonists-a-systematic-review-and-meta-analysis-of-randomised-controlled-trials
#10
Zheng Zhang, Wei Fan, Gui Yang, Zhigao Xu, June Wang, Qingyuan Cheng, Mingxia Yu
OBJECTIVES: An increased risk of tuberculosis (TB) has been reported in patients treated with TNF-α antagonists, an issue that has been highlighted in a WHO black box warning. This review aimed to assess the risk of TB in patients undergoing TNF-α antagonists treatment. METHODS: A systematic literature search for randomised controlled trials (RCTs) was performed in MEDLINE, Embase and Cochrane library and studies selected for inclusion according to predefined criteria...
March 22, 2017: BMJ Open
https://www.readbyqxmd.com/read/28333932/impairment-of-wnt-%C3%AE-catenin-signaling-in-blood-cells-of-patients-with-severe-cavitary-pulmonary-tuberculosis
#11
Lin Fan, Hongbo Shen, Huichang Huang, Rui Yang, Lan Yao
Tuberculosis (TB) remains as a leading infectious disease worldwide. Our previous study showed interferon (IFN)-γ and CD3 T cell impairment in patients with severe cavitary pulmonary TB (PTB). However, the cause of the change in immune responses during the progression of TB is still poorly understood. In this study, eight newly diagnosed patients with severe cavitary and mild lesion non-cavity PTB were recruited, and three healthy volunteers were recruited as the control. RNA extracted from blood was tested by whole genome oligo microarrays...
2017: PloS One
https://www.readbyqxmd.com/read/28333182/early-tuberculin-skin-test-for-the-diagnosis-of-latent-tuberculosis-infection-in-patients-with-inflammatory-bowel-disease
#12
Carlos Taxonera, Ángel Ponferrada, Fernando Bermejo, Sabino Riestra, Cristina Saro, María Dolores Martín-Arranz, José Luis Cabriada, Manuel Barreiro-de Acosta, María Luisa de Castro, Pilar López-Serrano, Jesús Barrio, Cristina Suarez, Eva Iglesias, Federico Argüelles-Arias, Isabel Ferrer, Ignacio Marín-Jiménez, Alejandro Hernández-Camba, Guillermo Bastida, Manuel Van Domselaar, Pilar Martínez-Montiel, David Olivares, Cristina Alba, Javier P Gisbert
Background and Aim: Sensitivity of tuberculin skin test [TST] during screening for latent tuberculosis infection [LTBI] is affected by steroid and/or immunosuppressant therapy. The aim of this study was to compare performance of the two-step TST in inflammatory bowel disease patients immediately before anti-tumour necrosis factor [TNF] therapy as part of routine screening for LTBI vs control patients when the TST was carried out at an early stage. Methods: In this multicentre prospective controlled study, we evaluated the performance of two-step TST with 5-mm threshold...
February 17, 2017: Journal of Crohn's & Colitis
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
#13
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/28314076/lactococcus-lactis-carrying-a-dna-vaccine-coding-for-the-esat-6-antigen-increases-il-17-cytokine-secretion-and-boosts-the-bcg-vaccine-immune-response
#14
Vanessa Bastos Pereira, Vanessa Pecini da Cunha, Tatiane Melo Preisser, Bianca Mendes Souza, Meritxell Zurita Turk, Camila Prósperi De Castro, Marcela Santiago Pacheco Azevedo, Anderson Miyoshi
AIMS: A regimen utilizing BCG and another vaccine system as a booster may represent a promising strategy for the development of an efficient tuberculosis vaccine for adults. In a previous work, we confirmed the ability of Lactococcus lactis FnBPA+ (pValac:ESAT-6), a live mucosal DNA vaccine, to produce a specific immune response in mice after oral immunization. In the present study, we examined the immunogenicity of this strain as a booster for the BCG vaccine in mice. METHODS AND RESULTS: After immunization, cytokine and immunoglobulin profiles were measured...
March 17, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28299430/alternative-quantiferon-cytokines-for-diagnosis-of-children-with-active-tuberculosis-and-hiv-co-infection-in-ghana
#15
Christian Lundtoft, Anthony Afum-Adjei Awuah, Norman Nausch, Anthony Enimil, Ertan Mayatepek, Ellis Owusu-Dabo, Marc Jacobsen
IFN-γ release assays (IGRAs) often present false-negative or indeterminate results in children with tuberculosis. HIV co-infection may contribute to decreased sensitivity of IGRAs by impairing T-cell IFN-γ expression. Measurement of alternative cytokines in QuantiFERON(®) (QFT) supernatants can circumvent the IFN-γ-dependency and may improve QFT sensitivity. We aimed to identify additional cytokines from QFT supernatants for detection of Mycobacterium tuberculosis infection in children with tuberculosis and HIV co-infection from Ghana...
March 15, 2017: Medical Microbiology and Immunology
https://www.readbyqxmd.com/read/28299403/effects-of-ifn-%C3%AE-1a-and-ifn-%C3%AE-1b-treatment-on-the-expression-of-cytokines-inducible-nos-nos-type-ii-and-myelin-proteins-in-animal-model-of-multiple-sclerosis
#16
Natalia Lubina-Dąbrowska, Adam Stepień, Grzegorz Sulkowski, Beata Dąbrowska-Bouta, Józef Langfort, Małgorzata Chalimoniuk
The aim of this study was to investigate the effects of interferon (IFN)-β1a and IFN-β1b treatment on inflammatory factors and myelin protein levels in the brain cortex of the Lewis rat experimental autoimmune encephalomyelitis (EAE), animal model of multiple sclerosis. To induce EAE, rat were immunized with inoculums containing spinal cord guinea pig homogenized in phosphate-buffered saline and emulsified in Freund's complete adjuvant containing 110 µg of the appropriate antigen in 100 µl of an emulsion and additionally 4-mg/ml Mycobacterium tuberculosis (H37Ra)...
March 15, 2017: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/28288508/isoniazid-treatment-for-latent-tuberculosis-infection-is-tolerable-for-rheumatoid-arthritis-patients-receiving-tumor-necrosis-factor-inhibitor-therapy
#17
Yoon-Kyoung Sung, Soo-Kyung Cho, Dam Kim, Soyoung Won, Chan-Bum Choi, Tae-Hwan Kim, Jae-Bum Jun, Dae-Hyun Yoo, Sang-Cheol Bae
Background/Aims: To evaluate the impact of isoniazid (INH) treatment for latent tuberculosis infection (LTBI) on the development of liver function test (LFT) abnormality and the persistence of tumor necrosis factor (TNF) inhibitors in rheumatoid arthritis (RA) patients. Methods: We retrospectively enrolled patients with RA who were treated with TNF inhibitors at a university hospital between December 2000 and November 2011. After dividing the patients into two groups based on the occurrence of LFT abnormality during follow-up, we compared demographic and clinical features between the two groups...
March 13, 2017: Korean Journal of Internal Medicine
https://www.readbyqxmd.com/read/28280495/myeloid-and-t-cell-derived-tnf-protects-against-central-nervous-system-tuberculosis
#18
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/28272457/novel-vaccine-potential-of-rv3131-a-dosr-regulon-encoded-putative-nitroreductase-against-hyper-virulent-mycobacterium-tuberculosis-strain-k
#19
Kee Woong Kwon, Woo Sik Kim, Hongmin Kim, Seung Jung Han, Mi-Young Hahn, Jong Seok Lee, Ki Taek Nam, Sang-Nae Cho, Sung Jae Shin
Accumulating evidence indicates that latency-associated Mycobacterium tuberculosis (Mtb)-specific antigens from the dormancy survival regulator regulon (DosR) may be promising novel vaccine target antigens for the development of an improved tuberculosis vaccine. After transcriptional profiling of DosR-related genes in the hyper-virulent Beijing Mtb strain K and the reference Mtb strain H37Rv, we selected Rv3131, a hypothetical nitroreductase, as a vaccine antigen and evaluated its vaccine efficacy against Mtb K...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270399/tuberculous-periprosthetic-infection-precipitated-by-infliximab-therapy
#20
Rajesh Malhotra, Deepak Gautam, Naman Wahal
Biological therapy with TNF-α inhibitors have been increasingly used in the treatment of inflammatory arthritis. Systemic tuberculosis infections are often known to occur following treatment with these biological agents. However, no case of periprosthetic tuberculous infection of the hip following this therapy has been reported. We report a case of a 45-year-old man who developed periprosthetic tuberculous infection soon after infliximab injection. We also discuss the need of pretreatment awareness, high index of suspicion, early diagnosis and management of such case...
March 7, 2017: BMJ Case Reports
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