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TB cytokine

Djalma A Alves da Silva, Marcos V da Silva, Cleyson C Oliveira Barros, Patrícia B Dias Alexandre, Rodolfo P Timóteo, Jonatas S Catarino, Helioswilton Sales-Campos, Juliana R Machado, Denise B R Rodrigues, Carlo J Oliveira, Virmondes Rodrigues
Tuberculosis (TB) is a granulomatous disease that has affected humanity for thousands of years. The production of cytokines, such as IFN-γ and TNF-α, is fundamental in the formation and maintenance of granulomas and in the control of the disease. Recently, the introduction of TNF-α-blocking monoclonal antibodies, such as Infliximab, has brought improvements in the treatment of patients with chronic inflammatory diseases, but this treatment also increases the risk of reactivation of latent tuberculosis. Our objective was to analyze, in an in vitro model, the influence of Infliximab on the granulomatous reactions and on the production of antigen-specific cytokines (TNF-α, IFN-γ, IL-12p40, IL-10 and IL-17) from beads sensitized with soluble Bacillus Calmette-Guérin (BCG) antigens cultured in the presence of peripheral blood mononuclear cells (PBMC) from TB patients...
2018: PloS One
Marco Pio La Manna, Valentina Orlando, Paolo Li Donni, Guido Sireci, Paola Di Carlo, Antonio Cascio, Francesco Dieli, Nadia Caccamo
We used the Luminex Bead Array Multiplex Immunoassay to measure cytokines, chemokines and growth factors responses to the same antigens used for RD1-based Interferon γ Release Assay (IGRA) test. Seventy-nine individuals, 27 active TB, 32 latent infection subsets, 20 individuals derivative purified protein (PPD) negative (subjects that do not have any indurative cutaneous reaction after 72 hrs of intradermal injection of PPD) and with other pulmonary disease were retrospectively studied. Forty-eight analytes were evaluated by Luminex Assay in plasma obtained from whole blood stimulated cells...
2018: PloS One
Natália B Carvalho, Maria de Lourdes Bastos, Anselmo S Souza, Eduardo M Netto, Sérgio Arruda, Silvane B Santos, Edgar M Carvalho
IFN-γ and TNF play critical roles in the control of Mycobacterium tuberculosis infection. Despite leading to an exaggerated production of inflammatory cytokines, HTLV-1 infection increases the risk of developing tuberculosis (TB). However, the immune mechanisms accounting for this phenomenon are still unclear. The aim of this study was to evaluate immunological aspects of the HTLV-1/M. tuberculosis co-infection. In this cross-sectional study, the levels of TNF, IL-1β, and IL-17 were determined by ELISA in the supernatants of either unstimulated or tuberculin purified protein derivative (PPD) stimulated peripheral blood mononuclear cells...
January 2018: Tuberculosis
Sally A F El-Sahrigy, Azza M O Abdel Rahman, Dalia Y Samaha, Nesrine A Mohamed, Sally M Saber, Hala A Talkhan, Ghada A Ismail, Essam M Ibraheem, Emad M Riad
INTRODUCTION: Tuberculosis (TB) remains a huge worldwide burden, despite extensive vaccination coverage with the Bacillus Calmette-Guérin (BCG), the only vaccine available against this disease, indicating that BCG-driven immunity is inadequate to protect the human population against TB. This underscore the critical necessitate to develop an improved TB vaccine, based on a better understanding of host-pathogen interactions and immune responses during mycobacterial infection. AIM OF THE WORK: To examine whether the exogenous addition of IFN-β could improve dendritic cell (DC) response to Mycobacterium bovis (M...
March 6, 2018: Journal of Immunological Methods
Mathieu Garand, Martin Goodier, Olumuyiwa Owolabi, Simon Donkor, Beate Kampmann, Jayne S Sutherland
Tuberculosis (TB) is still a global health concern, especially in resource-poor countries such as The Gambia. Defining protective immunity to TB is challenging: its pathogenesis is complex and involves several cellular components of the immune system. Recent works in vaccine development suggest important roles of the innate immunity in natural protection to TB, including natural killer (NK) cells. NK cells mediate cellular cytotoxicity and cytokine signaling in response to Mycobacterium tuberculosis (Mtb). NK cells can display specific memory-type markers to previous antigen exposure; thus, bridging innate and adaptive immunity...
2018: Frontiers in Immunology
Shahrad Hakimian, Yevgeniy Popov, Abbas H Rupawala, Karen Salomon-Escoto, Steven Hatch, Randall Pellish
Background: Tumor necrosis factor alpha (TNFα) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFα medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI. Methods: We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications...
2018: Biologics: Targets & Therapy
Peter Hart, Alastair Copland, Gil Reynolds Diogo, Shane Harris, Ralf Spallek, Wulf Oehlmann, Mahavir Singh, Juan Basile, Martin Rottenberg, Matthew John Paul, Rajko Reljic
Tuberculosis (TB) is the leading cause of death from infectious disease, and the current vaccine, Bacillus Calmette-Guerin (BCG), is inadequate. Nanoparticles (NPs) are an emerging vaccine technology, with recent successes in oncology and infectious diseases. NPs have been exploited as antigen delivery systems and also for their adjuvantic properties. However, the mechanisms underlying their immunological activity remain obscure. Here, we developed a novel mucosal TB vaccine (Nano-FP1) based upon yellow carnauba wax NPs (YC-NPs), coated with a fusion protein consisting of three Mycobacterium tuberculosis (Mtb) antigens: Acr, Ag85B, and HBHA...
March 7, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
Tilman E Klassert, Surabhi Goyal, Magdalena Stock, Dominik Driesch, Abid Hussain, Luis Carlos Berrocal-Almanza, Rajashekar Myakala, Gaddam Sumanlatha, Vijayalakshmi Valluri, Niyaz Ahmed, Ralf R Schumann, Carlos Flores, Hortense Slevogt
Tuberculosis (TB) is a multifactorial disease governed by bacterial, host and environmental factors. On the host side, growing evidence shows the crucial role that genetic variants play in the susceptibility to Mycobacterium tuberculosis (Mtb) infection. Such polymorphisms have been described in genes encoding for different cytokines and pattern recognition receptors (PRR), including numerous Toll-like receptors (TLRs). In recent years, several members of the C-type lectin receptors (CTLRs) have been identified as key PRRs in TB pathogenesis...
2018: Frontiers in Immunology
Paulo Ranaivomanana, Mihaja Raberahona, Sedera Rabarioelina, Ysé Borella, Alice Machado, Mamy J De Dieu Randria, Rivo A Rakotoarivelo, Voahangy Rasolofo, Niaina Rakotosamimanana
Background: The primary site of infection for Mycobacterium tuberculosis ( Mtb ) is the alveolar macrophages. However, Mtb can disseminate into other organs and causes extrapulmonary tuberculosis (EPTB). The diagnosis of EPTB is challenging due to relatively inaccessible infectious sites that may be paucibacillary and with clinical symptoms varying by site that are similar to those seen in other diseases. Hence, we sought to identify the expression patterns of a variety of cytokines that may be specific to EPTB from in vitro infections and in the plasma of TB patients...
2018: Frontiers in Microbiology
Nallely Lopez-Lopez, Ana Gabriela Ramos Martinez, Mariana Haydee Garcia-Hernandez, Rogelio Hernandez-Pando, Julio Enrique Castañeda-Delgado, Geanncarlo Lugo-Villarino, Céline Cougoule, Olivier Neyrolles, Bruno Rivas-Santiago, Monica Alejandra Valtierra-Alvarado, Marisela Rubio-Caceres, Jose Antonio Enciso-Moreno, Carmen Judith Serrano
BACKGROUND: Type 2 diabetes (T2D) is a risk factor for the development of tuberculosis (TB), although the associated mechanisms are not known. OBJECTIVES: To study the association between T2D and the basal phenotype of macrophages, and their immune response to Mycobacterium tuberculosis (Mtb) infection. METHODS: We evaluated the influence of T2D on the response of monocyte-derived macrophages (MDM) to Mtb in patients with T2D (n = 10) compared to healthy subjects (n = 9), before and after infection with Mtb clinical isolates bearing different degrees of virulence...
February 19, 2018: Memórias do Instituto Oswaldo Cruz
A A Alshevskaya, F D Kireev, Z A Laushkina, J A Lopatnikova, V S Gladkikh, J A Sennikova, A V Karaulov, S V Sennikov
BACKGROUND: Tumour necrosis factor-alpha (TNF-α) and its inhibitors are involved in both defence against tuberculosis (TB) and damage to the host by TB. Notably, the change in receptor expression on cell density is a key mechanism in regulation of the biological properties of cytokines. OBJECTIVE: To study the differences in TNF-α receptor (TNFR) expression in patients with active pulmonary tuberculosis (aPTB) in correlation with the parameters of disease severity...
February 1, 2018: International Journal of Tuberculosis and Lung Disease
Hicret Islamoglu, Ruoqiong Cao, Garrett Teskey, Karo Gyurjian, Sebastian Lucar, Marcel P Fraix, Airani Sathananthan, John K Chan, Vishwanath Venketaraman
Mycobacterium tuberculosis ( M. tb ), a rod-shaped acid-fast bacterium, is the causative agent of tuberculosis (TB). TB remains one of the leading causes of morbidity and mortality worldwide. Additionally, approximately one-third of the world's population has latent tuberculosis infection (LTBI) as a result of the body's primary mechanism of defense against M. tb infection, the formation of a granuloma. A granuloma is the aggregation of immune cells that encapsulate the bacteria to keep them localized to prevent further infection and thus the bacteria become quiescent...
March 1, 2018: Journal of Clinical Medicine
I C van Rensburg, L du Toit, G Walzl, N du Plessis, A G Loxton
MicroRNAs are short non-coding RNAs that regulate gene expression by binding to, and suppressing the expression of genes. Research show that microRNAs have potential to be used as biomarkers for diagnosis, treatment response and can be used for therapeutic interventions. Furthermore, microRNA expression has effects on immune cell functions, which may lead to disease. Considering the important protective role of neutrophils and B-cells during M.tb infection, we evaluated the expression of microRNAs, known to alter function of these cells, in the context of human TB...
February 22, 2018: Gene
Venkata Ramanarao Parasa, Jeronimo Rose, Luis Alberto Castillo-Diaz, Michel de Jesús Aceves-Sánchez, Perla Jazmín Vega-Domínguez, Maria Lerm, Mario Alberto Flores-Valdez
Tuberculosis (TB) still remains as an unmet global threat. The current vaccine is not fully effective and novel alternatives are needed. Here, two vaccine candidate strains derived from BCG carrying deletions in the BCG1416c or BCG1419c genes were analysed for their capacity to modulate the cytokine/chemokine profile and granuloma formation in a human lung tissue model (LTM). We show that the clustering of monocytes, reminiscent of early granuloma formation, in LTMs infected with BCG strains was similar for all of them...
February 20, 2018: Vaccine
L D'Attilio, A Díaz, R D V Fernández, B Bongiovanni, N Santucci, G Dídoli, S Lioi, W Gardeñez, J L Naninni, A Del Rey, H Besedovsky, O Bottasso, M L Bay
BACKGROUND: Tuberculosis (TB) is a major health problem worldwide. In TB, the immune and central nervous systems modulate each other. The two main components of this network are the hypothalamic-pituitary-adrenal axis (HPA) and autonomic nervous system (ANS). OBJECTIVE: To elucidate neuro-endocrine-immune (NEI) interactions in pulmonary (PTB) or pleural (PLTB) TB, we analysed the relationship among compounds from these systems. METHODS: We quantified levels of catecholamines, hormones and cytokines in plasma from patients with PTB (n = 46) or PLTB (n = 12) and controls (n = 32), and in the pleural fluid from PLTB patients...
March 1, 2018: International Journal of Tuberculosis and Lung Disease
Murugesan Harishankar, Harini Ravikrishnan, Akshaya Ravishankar, Luke Hanna Elizabeth, Soumya Swaminathan, Paramasivam Selvaraj, Ramalingam Bethunaickan
BACKGROUND: Genetic factors play an important role in the development of disease susceptibility or protection. Cytokine gene polymorphisms are reported to be associated with altered levels of cytokine production that can impact disease progression in HIV and TB. OBJECTIVE: In this study, we studied IL-10 -592(C/A) and TGF-β -509 (C/T) promoter polymorphisms to understand their role in susceptibility or resistance to HIV and TB in a South Indian population. METHOD: Genomic DNA was isolated from healthy controls, pulmonary tuberculosis patients (n=122) and HIV positive individuals (n=100) and used for genotyping by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) method...
February 19, 2018: Current HIV Research
Simone A Joosten, Krista E van Meijgaarden, Sandra M Arend, Corine Prins, Fredrik Oftung, Gro Ellen Korsvold, Sandra V Kik, Rob Jw Arts, Reinout van Crevel, Mihai G Netea, Tom Hm Ottenhoff
The lack of defined correlates of protection hampers development of vaccines against tuberculosis (TB). In vitro mycobacterial outgrowth assays are thought to better capture the complexity of the human host/Mycobacterium tuberculosis (Mtb) interaction. We used a PBMC-based "mycobacterial-growth-inhibition-assay" (MGIA) to investigate the capacity to control outgrowth of Bacille Calmette-Guérin (BCG). Interestingly, strong control of BCG outgrowth was observed almost exclusively in individuals with recent exposure to Mtb, but not in (long-term) latent TB infection, and only modestly in BCG vaccinees...
February 20, 2018: Journal of Clinical Investigation
Natalie E Nieuwenhuizen, Stefan H E Kaufmann
Tuberculosis (TB), caused by the intracellular bacterium Mycobacterium tuberculosis (Mtb), remains a major health threat. A live, attenuated mycobacterium known as Bacille Calmette-Guérin (BCG), derived from the causative agent of cattle TB, Mycobacterium bovis , has been in clinical use as a vaccine for 90 years. The current incidence of TB demonstrates that BCG fails to protect sufficiently against pulmonary TB, the major disease manifestation and source of dissemination. The protective efficacy of BCG is on average 50% but varies substantially with geographical location and is poorer in those with previous exposure to mycobacteria...
2018: Frontiers in Immunology
Xiaojuan Ren, Wei Liu, Yi Liu
With overuse of the broad-spectrum antibiotics, the pulmonary fungal infection increasingly becomes the most common complication associated with senile pulmonary tuberculosis (TB) and attracts intensive attentions from clinicians. Here we presented the retrospective analysis of impact of fluconazole treatment on the clinical outcome and immune response in fungal co-infected tuberculosis patients. A randomized, double-blind, placebo-controlled trial of fluconazole (100 mg per day for consecutive weeks) in fungal-positive senile tuberculosis patients was conducted in our hospital...
February 9, 2018: Microbial Pathogenesis
Ruchi Rastogi, Arbind Kumar, Jagdeep Kaur, Varinder Saini, Jasbinder Kaur, Archana Bhatnagar
The genome sequence of Mycobacterium tuberculosis revealed the presence of several hydrolases involved in lipid metabolism including the members of Lip gene family. Rv0646c (LipG) is one of them. It is annotated as putative esterase/lipase because of the presence of consensus sequence 'GXSXG.' The gene was cloned, expressed, and purified in E. coli. It showed 22 U/mg specific activity with pNP-butyrate as a preferred substrate. However, it actively worked on substrates with short chain. The enzyme was optimally active at 50 °C/pH 8...
January 31, 2018: Molecular and Cellular Biochemistry
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