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https://www.readbyqxmd.com/read/29243495/the-recombinant-fusion-protein-cfp10-esat6-difn-has-protective-effect-against-tuberculosis-in-guinea-pigs
#1
Natalya V Permyakova, Pavel A Belavin, Dariya S Pirozhkova, Elena G Ufimtseva, Sergey M Rozov, Sergey R Mursalimov, Yuriy V Sidorchuk, Elena A Uvarova, Alla A Zagorskaya, Tatiana V Marenkova, Svetlana V Bannikova, Evgeniy A Demidov, Konstantin V Starostin, Marionella A Kravchenko, Diana V Vakhrusheva, Roman B Berdnikov, Natalya I Eremeeva, Sergey N Skornyakov, Sergey E Peltek, Elena V Deineko
Development of effective vaccine candidates against tuberculosis (TB) is currently the most important challenge in the prevention of this disease since the BCG vaccine fails to guarantee a lifelong protection, while any other approved vaccine with better efficiency is still absent. The protective effect of the recombinant fusion protein CFP10-ESAT6-dIFN produced in a prokaryotic expression system (Escherichia coli) has been assessed in a guinea pig model of acute TB. The tested antigen comprises the Mycobacterium tuberculosis (Mtb) proteins ESAT6 and CFP10 as well as modified human γ-interferon (dIFN) for boosting the immune response...
December 15, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/29242190/the-rv2633c-protein-of-mycobacterium-tuberculosis-is-a-non-heme-di-iron-catalase-with-a-possible-role-in-defenses-against-oxidative-stress
#2
Zhongxin Ma, Kyle T Strickland, Michelle D Cherne, Esha Sehanobish, Kyle H Rohde, William T Self, Victor L Davidson
The Rv2633c gene in Mycobacterium tuberculosis is rapidly upregulated after macrophage infection, suggesting that Rv2633c is involved in M. tuberculosis pathogenesis. However, the activity and role of the Rv2633c protein in host colonization is unknown. Here, we analyzed the Rv2633c protein sequence, which revealed the presence of an HHE cation-binding domain common in hemerythrin-like proteins. Phylogenetic analysis indicated that Rv2633c is a member of a distinct subset of hemerythrin-like proteins exclusive to mycobacteria...
December 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29239661/enhancement-of-the-antimycobacterial-activity-of-macrophages-by-ajoene
#3
Ji-Ae Choi, Soo-Na Cho, Yun-Ji Lim, Junghwan Lee, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Ajoene, a garlic-derived sulfur-containing compound, has broad-spectrum antimicrobial activity. To assess the potential of ajoene for treating tuberculosis (TB), we determined whether it induces the stress response of the endoplasmic reticulum (ER), which plays an important role in TB. We showed that ajoene stimulation induced the production of ER stress sensor molecules and reactive oxygen species (ROS) levels. Ajoene-induced ROS production was dependent on c-Jun N-terminal kinase (JNK) activation. Interestingly, the inhibition of JNK activity and suppression of ROS production reduced ajoene-induced CHOP production in macrophages...
January 1, 2017: Innate Immunity
https://www.readbyqxmd.com/read/29236768/autophagy-induction-by-mycobacterium-indicus-pranii-promotes-mycobacterium-tuberculosis-clearance-from-raw-264-7-macrophages
#4
Bindu Singh, Mohd Saqib, Ananya Gupta, Pawan Kumar, Sangeeta Bhaskar
Mycobacterium indicus pranii (MIP) is a potent vaccine candidate against tuberculosis (TB) as it has demonstrated significant protection in animal models of tuberculosis as well as in clinical trials. Higher protective efficacy of MIP against TB as compared to BCG provoked the efforts to gain insight into the molecular mechanisms underlying MIP mediated protection against Mycobacterium tuberculosis (M.tb). Autophagy, initially described as a cell survival mechanism during starvation, also plays a key role in host resistance to M...
2017: PloS One
https://www.readbyqxmd.com/read/29233902/t-cell-production-of-gm-csf-protects-the-host-during-experimental-tuberculosis
#5
Richard T Robinson
Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection with Mycobacterium tuberculosis and is necessary to restrict M. tuberculosis growth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017, https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance...
December 12, 2017: MBio
https://www.readbyqxmd.com/read/29233104/tlr4-nox2-axis-regulates-the-phagocytosis-and-killing-of-mycobacterium-tuberculosis-by-macrophages
#6
Jingzhu Lv, Xiaoyan He, Hongtao Wang, Zhaohua Wang, Gabriel T Kelly, Xiaojing Wang, Yin Chen, Ting Wang, Zhongqing Qian
BACKGROUND: Macrophages stand at the forefront of both innate and adapted immunity through their capacities to recognize, engulf, and eliminate foreign particles, and to stimulate adapted immune cells. They are also involved in controlling pro- and anti-inflammatory pathways. Macrophage activity against Mycobacterium tuberculosis (M. tuberculosis) has been shown to involve Toll-like receptor (TLR) activation and ROS production. Previous studies have shown that lipopolysaccharide (LPS), through TLR4, could activate macrophages, improve their bactericidal ROS production, and facilitate anti-infective immune responses...
December 12, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29230224/lipoarabinomannan-decreases-galectin-9-expression-and-tumor-necrosis-factor-pathway-in-macrophages-favoring-mycobacterium-tuberculosis-intracellular-growth
#7
Leslie Chávez-Galán, Lucero Ramon-Luing, Claudia Carranza, Irene Garcia, Isabel Sada-Ovalle
Lipoarabinomannan (LAM) is a lipid virulent factor secreted by Mycobacterium tuberculosis (Mtb). LAM can be found in the sputum and urine of patients with active tuberculosis. When human monocytes are differentiated into macrophages [monocyte-derived macrophages (MDM)] in the presence of LAM, MDM are poorly functional which may limit the immune response to Mtb infection. Our previous studies have shown that TIM3 and galectin (GAL)9 interaction induces anti-mycobacterial activity, and the expression levels of TIM3 and GAL9 are downregulated during Mtb infection...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29229989/necroptotic-signaling-is-primed-in-mycobacterium-tuberculosis-infected-macrophages-but-its-pathophysiological-consequence-in-disease-is-restricted
#8
Michael D Stutz, Samar Ojaimi, Cody Allison, Simon Preston, Philip Arandjelovic, Joanne M Hildebrand, Jarrod J Sandow, Andrew I Webb, John Silke, Warren S Alexander, Marc Pellegrini
Mixed lineage kinase domain-like (MLKL)-dependent necroptosis is thought to be implicated in the death of mycobacteria-infected macrophages, reportedly allowing escape and dissemination of the microorganism. Given the consequent interest in developing inhibitors of necroptosis to treat Mycobacterium tuberculosis (Mtb) infection, we used human pharmacologic and murine genetic models to definitively establish the pathophysiological role of necroptosis in Mtb infection. We observed that Mtb infection of macrophages remodeled the intracellular signaling landscape by upregulating MLKL, TNFR1, and ZBP1, whilst downregulating cIAP1, thereby establishing a strong pro-necroptotic milieu...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229273/mannose-functionalized-solid-lipid-nanoparticles-are-effective-in-targeting-alveolar-macrophages
#9
Ana Costa, Bruno Sarmento, Vítor Seabra
Mannose receptor is highly expressed on alveolar macrophages, being a potential target to promote the specific local drug delivery of anti-tuberculosis agents through the use of functionalized nanocarriers. In this work, isoniazid (Isn)-loaded solid lipid nanoparticles (SLN), reinforced with stearylamine (SA) were produced by double emulsion technique and further surface-functionalized with mannose in a straightforward chemical approach. Upon pre-formulation assessment, SLN close to 500 nm average size, positively charged and with association efficiency of ISN close to 50% were obtained...
December 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29225091/gene-expression-profiling-of-the-trim-protein-family-reveals-potential-biomarkers-for-indicating-tuberculosis-status
#10
Yanqing Chen, Shuhui Cao, Yong Sun, Chuanyou Li
Tripartite motif (TRIM) family proteins play important regulatory roles in innate immune responses, the dysregulation of which cause several infectious diseases. However, the role and function of TRIM family proteins during tuberculosis (TB) infection remains unclear. In this study, we employed real-time quantitative PCR to profile the transcript levels of 72 TRIM genes from a cohort of 5 active TB patients, 5 latent tuberculosis infection (LTBI) subjects, and 5 healthy controls (HCs) in an initial discovery phase...
December 7, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29219321/sheta2-dry-powder-aerosols-for-tuberculosis-formulation-design-and-optimization-using-quality-by-design
#11
Mariam Ibrahim, Manolya Kukut Hatipoglu, Lucila Garcia-Contreras
Tuberculosis (TB) is a life threatening pulmonary infection caused by Mycobacterium tuberculosis (MTB). Current treatments are complex, lengthy and associated with severe side effects that decrease patient compliance and increase the probability of the emergence of drug resistant strains. Thus, more effective drugs with little to no side effects are needed to diversify the armamentarium against the global TB epidemic. SHetA2, an anticancer compound with null toxicity at doses much higher than the effective dose, was recently discovered to be active against MTB...
December 8, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29219058/macrophage-targeted-cellular-carriers-for-effective-delivery-of-anti-tubercular-drugs
#12
S Beg, Jaya Agnihotri, Shibhna Singh, Mohammad Wais
Newly developed vaccine VPM1002 confers paradigm swing in the prophylactic treatment of tuberculosis (TB).Multi drug resistant and latent TB in adults as well as in underprivileged patients is instigating menace over world population if the host is immune-compromised. One third of the world's population is infected with TB. Recently it is estimated around 9.6 million people around the world became sick with TB disease. There were 1.5 million TB-related deaths worldwide. Therefore with the advent in biotechnology and Nano engineering, newly adapted survival molecular mechanism of Mycobacterium tuberculosis, new targets receptors on alveolar macrophages must be explored out for eradication of TB from the globe...
December 7, 2017: Recent Patents on Anti-infective Drug Discovery
https://www.readbyqxmd.com/read/29218036/the-macrophage-a-disputed-fortress-in-the-battle-against-mycobacterium-tuberculosis
#13
REVIEW
Christophe J Queval, Roland Brosch, Roxane Simeone
Mycobacterium tuberculosis (Mtb), the etiological agent of human tuberculosis (TB), has plagued humans for thousands of years. TB still remains a major public health problem in our era, causing more than 4,400 deaths worldwide every day and killing more people than HIV. After inhaling Mtb-contaminated aerosols, TB primo-infection starts in the terminal lung airways, where Mtb is taken up by alveolar macrophages. Although macrophages are known as professional killers for pathogens, Mtb has adopted remarkable strategies to circumvent host defenses, building suitable conditions to survive and proliferate...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29209302/influence-of-stress-and-antibiotic-resistance-on-cell-length-distribution-in-mycobacterium-tuberculosis-clinical-isolates
#14
Srinivasan Vijay, Dao N Vinh, Hoang T Hai, Vu T N Ha, Vu T M Dung, Tran D Dinh, Hoang N Nhung, Trinh T B Tram, Bree B Aldridge, Nguyen T Hanh, Do D A Thu, Nguyen H Phu, Guy E Thwaites, Nguyen T T Thuong
Mycobacterial cellular variations in growth and division increase heterogeneity in cell length, possibly contributing to cell-to-cell variation in host and antibiotic stress tolerance. This may be one of the factors influencing Mycobacterium tuberculosis persistence to antibiotics. Tuberculosis (TB) is a major public health problem in developing countries, antibiotic persistence, and emergence of antibiotic resistance further complicates this problem. We wanted to investigate the factors influencing cell-length distribution in clinical M...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29208960/mif-173-g%C3%A2-%C3%A2-c-rs755622-gene-polymorphism-modulates-tuberculosis-risk-evidence-from-a-meta-analysis-and-trial-sequential-analysis
#15
Mohammed Y Areeshi, Raju K Mandal, Sajad A Dar, Arshad Jawed, Mohd Wahid, Mohtashim Lohani, Aditya K Panda, B N Mishra, Naseem Akhter, Shafiul Haque
The macrophage migration inhibitory factor (MIF) is a cytokine that plays an important role in inhibiting the growth of pathogenic Mycobacterium tuberculosis (M.tb) and regulates immune responses against M.tb pathogen. MIF -173 G > C gene polymorphism may affect immunity in an individual and leads to susceptibility to tuberculosis (TB). A large number of studies have investigated the relevance of this polymorphism with TB risk, but their results were inconclusive. To obtain a precise conclusion, a meta-analysis was performed by retrieving six eligible studies from Google Scholar, PubMed (Medline), and EMBASE online databases...
December 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29208761/priming-of-innate-antimycobacterial-immunity-by-heat-killed-listeria-monocytogenes-induces-sterilizing-response-in-the-adult-zebrafish-tuberculosis-model
#16
Hanna Luukinen, Milka Marjut Hammarén, Leena-Maija Vanha-Aho, Aleksandra Svorjova, Laura Kantanen, Sampsa Järvinen, Bruno Vincent Luukinen, Eric Dufour, Mika Rämet, Vesa Pekka Hytönen, Mataleena Parikka
Mycobacterium tuberculosis remains one of the most problematic infectious agents due to its highly developed mechanisms to evade host immune responses combined with the increasing emergence of antibiotic resistance. Host-directed therapies aiming at optimal modulation of immune responses to improve bacterial eradication or to limit excessive inflammation are a new strategy for the treatment of tuberculosis. In this study, we have established a zebrafish-Mycobacterium marinum natural host-pathogen model system to study induced protective immune responses in mycobacterial infection...
November 30, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/29205566/transglutaminase-type-2-plays-a-key-role-in-the-pathogenesis-of-mycobacterium-tuberculosis-infection
#17
I Palucci, I Matic, L Falasca, M Minerva, G Maulucci, M De Spirito, E Petruccioli, D Goletti, F Rossin, M Piacentini, G Delogu
BACKGROUND: Mycobacterium tuberculosis (MTB), the aetiological agent of tuberculosis (TB), is capable of interfering with the phagosome maturation pathway, by inhibiting phagosome-lysosome fusion and the autophagic process to ensure survival and replication in macrophages. Thus, it has been proposed that the modulation of autophagy may represent a therapeutic approach to reduce MTB viability by enhancing its clearance. OBJECTIVE: The aim of this study was to investigate whether transglutaminase type 2 (TG2) is involved in the pathogenesis of MTB...
December 4, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/29204139/mycobacterium-tuberculosis-latent-antigen-rv2029c-from-the-multistage-dna-vaccine-a39-drives-th1-responses-via-tlr-mediated-macrophage-activation
#18
Haibo Su, Shengling Zhu, Lin Zhu, Cong Kong, Qi Huang, Zhi Zhang, Honghai Wang, Ying Xu
Targeting of Mycobacterium tuberculosis (MTB) latent antigens comprises a crucial strategy for the development of alternative tuberculosis (TB) vaccine(s) that protects against TB reactivation. Here, we generated a multistage DNA vaccine, A39, containing the early antigens Ag85A and Rv3425 as well as the latency-associated protein Rv2029c, which conferred protective immunity in a pre-exposure mouse model. Moreover, administration of the A39 vaccination after MTB exposure inhibited reactivation and resulted in significantly lower bacterial loads in the lungs and spleen of mice, compared to those in the control population...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29198784/pathogenesis-of-tuberculosis-and-other-mycobacteriosis
#19
Pere-Joan Cardona
The evolution between Mycobacterium tuberculosis infection and active tuberculosis is multifactorial and involves different biological scales. The synthesis of ESAT-6 or the induction of alveolar macrophage necrosis are key, but to understand it, it is necessary to consider the dynamics of endogenous and exogenous reinfection, drainage of lung parenchyma and respiratory mechanics, local fibrosis processes and blood supply. Paradoxically, the immune response generated by the infection is highly protective (90%) against active tuberculosis, although as it is essentially based on the proliferation of Th1 lymphocytes, it cannot prevent reinfection...
November 30, 2017: Enfermedades Infecciosas y Microbiología Clínica
https://www.readbyqxmd.com/read/29197526/pathway-analysis-of-differentially-expressed-genes-in-mycobacterium-bovis-challenged-bovine-macrophages
#20
Sanjeev Kumar Shukla, Shubhra Shukla, Anuj Chauhan, Sarvjeet, Rehan Khan, Anuj Ahuja, Lakshya Veer Singh, Nitin M Kamble, Anupam Dhasmana, Naveen Sharma, Bipin Chand, Ajay Vir Singh, Manjit Panigrahi
The immune signalling genes during challenge of bovine macrophages with bacterial products derived from disease causing bacteria in cattle were investigated. An in-vitro cell culture model were challenged to Mycobacterium bovis of bovine monocyte derived macrophages. Macrophages from healthy and already infected animals can both be fully activated during M. bovis infection. Analysis of mRNA abundance in peripheral blood mononuclear cells from M. bovis infected and non-infected cattle were performed as a controls...
November 29, 2017: Microbial Pathogenesis
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