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https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#1
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28625143/infection-and-malignancy-risk-in-patients-treated-with-tnf-inhibitors-for-immune-mediated-inflammatory-diseases
#2
Rui Pereira, Raquel Faria, Paula Lago, Tiago Torres
BACKGROUND: Infectious and malignant events are responsible for morbidity and mortality in patients with Immune-Mediated Inflammatory Diseases (IMIDs). Anti-tumor necrosis factor (Anti-TNF) agents appear to have an impact, however the individual effect of these agents in the different conditions is still unclear. OBJECTIVE: The goal of this study is to estimate the Incidence Rates (IR) of infections and malignancies in patients treated with anti-TNFs across different IMIDs, as well as potential risk factors...
June 15, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28620588/immunogenicity-and-protective-efficacy-of-a-fusion-protein-tuberculosis-vaccine-combining-five-esx-family-proteins
#3
Zhi-Hao Xiang, Rui-Feng Sun, Chen Lin, Fu-Zeng Chen, Jun-Tao Mai, Yu-Xiao Liu, Zi-Yan Xu, Lu Zhang, Jun Liu
One strategy to develop the next generation of tuberculosis vaccines is to construct subunit vaccines based on T cell antigens. In this study, we have evaluated the vaccine potential of a fusion protein combining EsxB, EsxD, EsxG, EsxU, and EsxM of Mycobacterium tuberculosis (M. tb). This recombinant protein, named BM, was expressed in and purified from Escherichia coli. Immunization of C57BL/6 mice with purified BM protein formulated in Freund's incomplete adjuvant induced the production of Th1 cytokines (IFN-γ, TNF, and IL-2) and multifunctional CD4(+) T cells...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28611779/diametric-role-of-the-latency-associated-protein-acr1-of-mycobacterium-tuberculosis-in-modulating-the-functionality-of-pre-and-post-maturational-stages-of-dendritic-cells
#4
Mohammed Amir, Mohammad Aqdas, Sajid Nadeem, Kaneez F Siddiqui, Nargis Khan, Javaid A Sheikh, Javed N Agrewala
It is instrumental for the Mycobacterium tuberculosis (Mtb) to persist within its host in dormancy. Mtb represses most of its metabolic machinery during latency, but upregulates the expression of latency-associated protein alpha-crystallin protein (Acr1). Therefore, it is imperative to understand how throughout dormancy, Mtb employs Acr1 to regulate the host immunity. This study reveals that Acr1 exhibits divergent effect on the pre- and post-maturation stages of dendritic cells (DCs). In the current study, we demonstrate that early encounter of bone marrow cells with Acr1 while differentiating into DCs (AcrDC(pre)), leads to impairment in their maturation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28610792/quantitative-and-qualitative-inkt-repertoire-associations-with-disease-susceptibility-and-outcome-in-macaque-tuberculosis-infection
#5
Andrew Chancellor, Andrew White, Anna S Tocheva, Joe R Fenn, Mike Dennis, Liku Tezera, Akul Singhania, Tim Elliott, Marc Tebruegge, Paul Elkington, Stephan Gadola, Sally Sharpe, Salah Mansour
Correlates of immune protection that reliably predict vaccine efficacy against Mycobacterium tuberculosis (Mtb) infection are urgently needed. Invariant NKT cells (iNKTs) are CD1d-dependent innate T cells that augment host antimicrobial immunity through production of cytokines, including interferon (IFN)-γ and tumour necrosis factor (TNF)-α. We determined peripheral blood iNKT numbers, their proliferative responses and iNKT subset proportions after in vitro antigen expansion by α-galactosylceramide (αGC) in a large cohort of mycobacteria-naïve non-human primates, and macaques from Bacillus Calmette-Guerin (BCG) vaccine and Mtb challenge studies...
July 2017: Tuberculosis
https://www.readbyqxmd.com/read/28605426/biomarkers-of-cerebral-injury-and-inflammation-in-pediatric-tuberculous-meningitis
#6
Ursula K Rohlwink, Katya Mauff, Katalin A Wilkinson, Nico Enslin, Emmanuel Wegoye, Robert J Wilkinson, Anthony A Figaji
Background: Tuberculous meningitis (TBM) leads to death or disability in half the affected individuals. Tools to assess severity and predict outcome are lacking. Neuro-specific biomarkers could serve as markers of the severity and evolution of brain injury, but have not been widely explored in TBM. We examined biomarkers of neurological injury (neuromarkers) and inflammation in pediatric TBM and their association with outcome. Methods: Blood and cerebrospinal fluid (CSF) of children with TBM and hydrocephalus taken on admission and over 3 weeks were analysed for neuromarkers S100B, neuron-specific enolase (NSE) and glial fibrillary acidic protein (GFAP), and multiple inflammatory markers...
June 9, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28589321/latent-tuberculosis-infection-and-tuberculosis-in-patients-with-rheumatic-diseases-treated-with-anti-tumor-necrosis-factor-agents
#7
Giovana Garziera, André Luis Bittencourt Morsch, Felipe Otesbelgue, Fernanda Luiza Staub, Penélope Esther Palominos, Claiton Viegas Brenol, Denise Rossato Silva
The introduction of biological agents, especially the tumor necrosis factor inhibitors (anti-TNF), for the treatment of rheumatic diseases increased the risk of developing tuberculosis (TB). Screening for latent TB infection (LTBI) is strongly recommended before starting therapy with anti-TNF agents. The objective of this study was to identify the prevalence of LTBI and TB among patients with rheumatic diseases on anti-TNF agents. This is a cross-sectional study. The electronic medical records of all adult patients (≥18 years old) undergoing anti-TNF treatment were reviewed...
June 6, 2017: Clinical Rheumatology
https://www.readbyqxmd.com/read/28588103/mycobacteriumtuberculosis-rv3615c-is-a-highly-immunodominant-antigen-and-specifically-inducespotent-th1-type-immune-responses-in-tuberculosis-pleurisy
#8
Jiangping Li, Juan Shen, Suihua Lao, Xiaomin Li, Jie Liu, Changyou Wu
T-cell responses have been demonstrated essential for preventing M.tb infection. The Th1-cytokines produced by T cells, such as INF-γ, IL-2 and TNF-α, not only limit the invasion of M.tb but also eliminate the pathogen at site of infection. BCG is known to induce Th1-type responses but the protection is inadequate. Identification of immunogenic components in addition to those expressed in BCG and induction of a broad spectrum of Th1-type responses provide options for generating sufficient adaptive immunity...
June 6, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28565847/recombinant-bacille-calmette-gu%C3%A3-rin-coexpressing-ag85b-ifn-%C3%AE-enhances-the-cell-mediated-immunity-in-c57bl-6-mice
#9
Wei Liu, Ying Xu, Hongbo Shen, Jingran Yan, Enzhuo Yang, Honghai Wang
The only available vaccine against pulmonary tuberculosis is Bacille Calmette-Guérin (BCG). As the efficacy reported of the vaccine is not up to the mark, there is an urgent need to develop improved anti-tuberculosis vaccines. Antigen 85B (Ag85B) is a very promising vaccine candidate molecule of Mycobacterium tuberculosis and interferon (IFN)-γ and has been considered the most attractive correlate of protective immunity. The aim of this study was to construct a novel recombinant BCG (rBCG) to secrete Ag85B and mouse IFN-γ under control of the Mycobacterial heat shock protein 60 (hsp60) promoter and the antigen signal sequence...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28558034/microrna-26a-mir-26a-klf4-and-creb-c-ebp%C3%AE-regulate-innate-immune-signaling-the-polarization-of-macrophages-and-the-trafficking-of-mycobacterium-tuberculosis-to-lysosomes-during-infection
#10
Sanjaya Kumar Sahu, Manish Kumar, Sohini Chakraborty, Srijon Kaushik Banerjee, Ranjeet Kumar, Pushpa Gupta, Kuladip Jana, Umesh D Gupta, Zhumur Ghosh, Manikuntala Kundu, Joyoti Basu
For efficient clearance of Mycobacterium tuberculosis (Mtb), macrophages tilt towards M1 polarization leading to the activation of transcription factors associated with the production of antibacterial effector molecules such as nitric oxide (NO) and proinflammatory cytokines such as interleukin 1 β (IL-1β) and tumor necrosis factor α (TNF-α). At the same time, resolution of inflammation is associated with M2 polarization with increased production of arginase and cytokines such as IL-10. The transcriptional and post-transcriptional mechanisms that govern the balance between M1 and M2 polarization, and bacteria-containing processes such as autophagy and trafficking of Mtb to lysosomes, are incompletely understood...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28547750/management-of-long-term-therapy-with-biological-drugs-in-psoriatic-patients-with-latent-tuberculosis-infection-in-real-life-setting
#11
Andrea Conti, Stefano Piaserico, Paolo Gisondi, Giulia Odorici, Giovanna Galdo, Claudia Lasagni, Giovanni Pellacani
Psoriatic patients with latent tuberculosis infection (LTBI) need a prophylaxis before starting a treatment with biological drugs. The aim of this study is to investigate the safety and efficacy of prophylaxis of LTBI in psoriatic patients receiving long-term biological drugs. The study included 56 patients (42 male and 14 female) affected by moderate-to-severe psoriasis (mean PASI: 12.8 ± 6.9 SD) treated with anti-TNF-α and/or anti IL 12, 23 and/or anti-CD11 drugs with a diagnosis of LTBI. LTBI diagnosis was based on tuberculin skin test and/or QuantiFERON TB Gold test positivity and chest X-ray suggestive, without clinical, or microbiological evidence of active disease...
May 26, 2017: Dermatologic Therapy
https://www.readbyqxmd.com/read/28545436/thymoquinone-tq-inhibits-the-replication-of-intracellular-mycobacterium-tuberculosis-in-macrophages-and-modulates-nitric-oxide-production
#12
Hafij Al Mahmud, Hoonhee Seo, Sukyung Kim, Md Imtiazul Islam, Kung-Woo Nam, Hyun-Deuk Cho, Ho-Yeon Song
BACKGROUND: Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent. METHODS: In this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages...
May 25, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28543876/application-of-molecular-microbiological-and-immunological-tests-for-the-diagnosis-of-bone-and-joint-tuberculosis
#13
Yinghua Tang, Lianli Yin, Shifu Tang, Hongyu Zhang, Jihui Lan
BACKGROUND: To evaluate the application of interferon gamma release assay (IGRA), rifampicin resistant real-time fluorescence quantitative PCR technique Xpert Mycobacterium tuberculosis/rifampicin (Xpert MTB/RIF), and the levels of TNF-α and TGF-β in the diagnosis of bone and joint tuberculosis. METHODS: Eighty-six patients with bone and joint tuberculosis, diagnosed by pathology or microbiology, were examined by Xpert MTB/RIF and IGRA (T-SPOT. TB) for Mycobacterium tuberculosis infection, and the TNF-α and TGF-β levels of the patients were measured...
May 22, 2017: Journal of Clinical Laboratory Analysis
https://www.readbyqxmd.com/read/28540757/association-of-tuberculosis-status-with-neurologic-disease-and-immune-response-in-htlv-1-infection
#14
Anselmo Souza, Natália Carvalho, Yuri Neves, Silvane Braga Santos, Maria de Lourdes Bastos, Sergio Arruda, Eduardo Martins Netto, Marshall Glesby, Edgar Carvalho
The human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 infected individuals have increased susceptibility to Mycobacterium tuberculosis infection but the influence of tuberculosis on the course of HTLV-1 infection is unknown. The aim of this study was to evaluate the influence of tuberculosis on immunological, virologic, and neurologic features of HTLV-1 infection. This is a retrospective analysis of individuals enrolled in a cohort study from an HTLV-1 clinic who were evaluated for past or latent tuberculosis and classified clinically as HTLV-1 carriers, probable HAM/TSP and definite HAM/TSP...
May 25, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28536578/expansion-of-cd25-negative-forkhead-box-p3-positive-t-cells-during-hiv-and-mycobacterium-tuberculosis-infection
#15
Matías T Angerami, Guadalupe V Suarez, María B Vecchione, Natalia Laufer, Diego Ameri, Graciela Ben, Hector Perez, Omar Sued, Horacio Salomón, María F Quiroga
Tuberculosis (TB) and HIV alter the immune system, and coinfected (HIV-TB) individuals usually present deregulations of T-lymphocytic immune response. We previously observed an increased frequency of "unconventional" CD4(+)CD25(-)FoxP3(+) Treg (uTreg) population during HIV-TB disease. Therefore, we aimed to explore the phenotype and function of uTreg and conventional CD4(+)CD25(+)FoxP3(+) Treg subsets (cTreg) in this context. We evaluated the expression of CD39, programmed cell death protein 1 (PD1), glucocorticoid-induced tumor necrosis factor receptor (GITR), and the effector/memory distribution by flow cytometry in cTreg and uTreg...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28536447/effects-of-hmasp-2-on-the-formation-of-bcg-infection-induced-granuloma-in-the-lungs-of-balb-c-mice
#16
Xiaoying Xu, Xiaoling Lu, Xingfang Dong, Yanping Luo, Qian Wang, Xun Liu, Jie Fu, Yuan Zhang, Bingdong Zhu, Xingming Ma
Tuberculosis, caused by Mycobacterium tuberculosis, affects the functions of the lung and causes high morbidity and mortality rates worldwide. MASP-2 is an executioner enzyme, which plays an essential role in the activation of lectin pathway. In our previous studies, the MASP-2 played a dual role in promoting the progress of lesions in BCG-infected rabbit skin models. However, the really effects of MASP-2 on tuberculosis are unknown. The aim of this study was to investigate the effects of MASP-2 in granuloma formation with BCG-infected mice...
May 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28535897/treatment-of-latent-tuberculosis-in-patients-with-juvenile-rheumatic-diseases-a-systematic-review
#17
José Cleosmaque Leite Júnior, Regina Terse Trindade Ramos, Teresa Cristina Martins Vicente Robazzi
INTRODUCTION: Children and adolescents with rheumatic diseases receiving TNF blockers are at risk for the activation of latent Mycobacterium tuberculosis infection (LTBI). Although LTBI treatment is indicated in this group, there are different therapeutic regimens in the literature, without a definite consensus. OBJECTIVES: To review in the literature therapeutic schemes used and indicated for the treatment of LTBI in these patients. METHODS: Systematic review of the literature, using health databases, selecting studies that addressed the treatment of LTBI in patients with juvenile rheumatic diseases using TNF blockers, from 1990 to 2015...
May 2017: Revista Brasileira de Reumatologia
https://www.readbyqxmd.com/read/28524434/unaffected-reaction-level-in-tuberculin-skin-test-by-long-term-therapy-with-tumor-necrosis-factor-inhibitors-for-rheumatoid-arthritis
#18
Shotaro Yamamoto, Katsuya Nagatani, Takeo Sato, Masahiro Iwamoto, Shino Takatori, Seiji Minota
AIM: The tuberculin skin test (TST) is used to diagnose tuberculosis; however, the influence of tumor necrosis factor (TNF) inhibitors on the test is unclear. This study investigated whether therapy with TNF inhibitors suppresses the TST reaction due to immunosuppression or whether the TST reaction increases due to reactivation of latent Mycobacterium tuberculosis infection. METHOD: Ninety-one patients with rheumatoid arthritis receiving TNF inhibitors (40 using infliximab and 51 using etanercept) were studied...
May 19, 2017: International Journal of Rheumatic Diseases
https://www.readbyqxmd.com/read/28507951/the-phytochemical-bergenin-enhances-t-helper-1-responses-and-anti-mycobacterial-immunity-by-activating-the-map-kinase-pathway-in-macrophages
#19
Ved P Dwivedi, Debapriya Bhattacharya, Vinod Yadav, Dhiraj K Singh, Santosh Kumar, Mona Singh, Durbadal Ojha, Anand Ranganathan, Luc Van Kaer, Debprasad Chattopadhyay, Gobardhan Das
Tuberculosis (TB) remains one of the greatest health concerns worldwide, which has hindered socioeconomic development in certain parts of the world for many centuries. Although current TB therapy, "Directly Observed Treatment Short-course," is effective, it is associated with unwanted side effects and the risk for the generation of drug-resistant organisms. The majority of infected individuals successfully confine the mycobacterial organisms and remain asymptotic unless immune responses are perturbed. Thus, host immunity can protect against TB and immunomodulation is therefore an attractive therapeutic option...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28507894/re-administration-of-abatacept-for-the-control-of-articular-symptoms-of-rheumatoid-arthritis-during-anti-tuberculous-therapy
#20
Hironori Kawamoto, Jin Takasaki, Satoru Ishii, Manabu Suzuki, Eriko Morino, Go Naka, Motoyasu Iikura, Shinyu Izumi, Yuichiro Takeda, Haruhito Sugiyama
This case report describes the re-administration of abatacept to successfully reduce the articularsymptoms of a patient with rheumatoid arthritisduring the intensive phase of anti-tuberculous therapy. A 75-year-old man developed active pulmonary tuberculosis during the administration of abatacept for rheumatoid arthritis. The patient experienced a paradoxical reaction and exacerbation of rheumatoid arthritis that caused us to discontinue the abatacept. Later re-administration of abatacept along with anti-tuberculosis treatment led to well-controlled rheumatoid arthritis without exacerbation of the tuberculosis...
2017: Respiratory Medicine Case Reports
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