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Tuberculosis and immune response

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https://www.readbyqxmd.com/read/28931237/histone-methyltransferase-set8-epigenetically-reprograms-host-immune-responses-to-assist-mycobacterial-survival
#1
Vikas Singh, Praveen Prakhar, R S Rajmani, Kasturi Mahadik, Salik Miskat Borbora, Kithiganahalli Narayanaswamy Balaji
NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28928738/age-stratified-t-cell-responses-in-children-infected-with-mycobacterium-tuberculosis
#2
Alexandra Dreesman, Véronique Corbière, Violette Dirix, Kaat Smits, Sara Debulpaep, Iris De Schutter, Myriam Libin, Mahavir Singh, Anne Malfroot, Camille Locht, Françoise Mascart
Tuberculosis (TB) in young children differs from adult TB in that the risk of rapid progression to active TB (aTB) is higher in children than in adults. The reasons for this increased risk are not fully understood. Early differentiation remains difficult between children at risk to develop aTB from those who will remain healthy and develop a latent TB infection (LTBI). Biomarkers to differentiate aTB from LTBI in children, especially in very young children, are urgently needed. To identify M. tuberculosis-specific functional T cell subsets related to clinical manifestations in children, we enrolled 87 children exposed to M...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28928442/genome-wide-association-and-hla-region-fine-mapping-studies-identify-susceptibility-loci-for-multiple-common-infections
#3
Chao Tian, Bethann S Hromatka, Amy K Kiefer, Nicholas Eriksson, Suzanne M Noble, Joyce Y Tung, David A Hinds
Infectious diseases have a profound impact on our health and many studies suggest that host genetics play a major role in the pathogenesis of most of them. We perform 23 genome-wide association studies for common infections and infection-associated procedures, including chickenpox, shingles, cold sores, mononucleosis, mumps, hepatitis B, plantar warts, positive tuberculosis test results, strep throat, scarlet fever, pneumonia, bacterial meningitis, yeast infections, urinary tract infections, tonsillectomy, childhood ear infections, myringotomy, measles, hepatitis A, rheumatic fever, common colds, rubella and chronic sinus infection, in over 200,000 individuals of European ancestry...
September 19, 2017: Nature Communications
https://www.readbyqxmd.com/read/28927311/successes-and-failures-in-human-tuberculosis-vaccine-development
#4
Roberto Zenteno-Cuevas
Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines...
September 19, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28920417/effects-of-deoxynivalenol-and-zearalenone-contaminated-feed-on-the-gene-expression-profiles-in-the-kidneys-of-piglets
#5
Kondreddy Eswar Reddy, Woong Lee, Jin Young Jeong, Yookyung Lee, Hyun-Jeong Lee, Min Seok Kim, Dong-Woon Kim, Dongjo Yu, Ara Cho, Young Kyoon Oh, Sung Dae Lee
Objective: Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN), common contaminants in the feed of farm animals, cause immune function impairment and organ inflammation. Consequently, the main objective of this study was to elucidate DON and ZEN effects on the mRNA expression of pro-inflammatory cytokines and other immune related genes in the kidneys of piglets. Methods: Fifteen 6-week-old piglets were randomly assigned to three dietary treatments for 4 weeks: control diet, and diets contaminated with either 8 mg DON/kg feed or 0...
September 18, 2017: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/28919416/identification-of-eukaryotic-udp-galactopyranose-mutase-inhibitors-using-the-thermofad-assay
#6
Julia S Martín Del Campo, Meital Eckshtain-Levi, Pablo Sobrado
Aspergillus fumigatus is a human pathogen responsible for deadly infections in immune-compromised patients. A potential strategy for treating A. fumigatus infections is by targeting the biosynthesis of cell wall components, such as galactofuranase, which is absent in humans. Galactofuranose biosynthesis is initiated by the flavoenzyme UDP-galactopyranose mutase (UGM), which converts UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf). UGM requires the reduced form of the flavin for activity, which is obtained by reacting it with NADPH...
September 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917925/synthesis-of-synthetic-mannan-backbone-polysaccharides-found-on-the-surface-of-mycobacterium-tuberculosis-as-a-vaccine-adjuvant-and-their-immunological-properties
#7
Chakree Wattanasiri, Jiraporn Paha, Marisa Ponpuak, Somsak Ruchirawat, Siwarutt Boonyarattanakalin
Surface components of Mycobacterium tuberculosis (Mtb) play crucial roles in modulating host immune responses. Thorough understandings of immunological properties of the Mtb's surface components are essential for the development of tuberculosis treatment and prevention. Unfortunately, the accessibility to the molecules on the surface of Mtb is limited by the structural complexity due to their various macromolecular nature and the hazard of culturing Mtb. In this study, we reveal a practical synthesis of lipomannan (LM) backbone polysaccharides - the core glycans found on Mtb's surface...
November 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28912729/multiplicity-of-mathematical-modeling-strategies-to-search-for-molecular-and-cellular-insights-into-bacteria-lung-infection
#8
REVIEW
Martina Cantone, Guido Santos, Pia Wentker, Xin Lai, Julio Vera
Even today two bacterial lung infections, namely pneumonia and tuberculosis, are among the 10 most frequent causes of death worldwide. These infections still lack effective treatments in many developing countries and in immunocompromised populations like infants, elderly people and transplanted patients. The interaction between bacteria and the host is a complex system of interlinked intercellular and the intracellular processes, enriched in regulatory structures like positive and negative feedback loops. Severe pathological condition can emerge when the immune system of the host fails to neutralize the infection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28911035/evaluation-of-pe_pgrs33-as-a-potential-surface-target-for-humoral-responses-against-mycobacterium-tuberculosis
#9
Mariachiara Minerva, Flavio De Maio, Serena Camassa, Basem Battah, Palucci Ivana, Riccardo Manganelli, Maurizio Sanguinetti, Michela Sali, Giovanni Delogu
Mycobacterium tuberculosis (Mtb) PE_PGRS33 is a surface-exposed protein that was shown to interact with Toll-like receptor 2 on host macrophages to induce inflammatory signals and promote entry in macrophages. In this study, we investigated PE_PGRS33 as a potential target of a humoral response aimed at hampering key processes in tuberculosis pathogenesis. PE_PGRS33 protein was successfully expressed and purified under native condition in Escherichia coli. The purified protein retained its native functional and biological properties, showing the ability to elicit proinflammatory signals in murine and human macrophages...
November 30, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28910983/quantitative-proteomic-analysis-of-host-responses-triggered-by-mycobacterium-tuberculosis-infection-in-human-macrophage-cells
#10
Hua Li, Sha Wei, Yuan Fang, Min Li, Xia Li, Zhe Li, Jibin Zhang, Guofeng Zhu, Chuanyou Li, Lijun Bi, Guimin Zhang, Dianbing Wang, Xian-En Zhang
Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria. Though the interaction between macrophages and mycobacteria has been widely investigated, the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear. In this work, we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28903115/erap1-and-pde8a-are-downregulated-in-cattle-protected-against-bovine-tuberculosis
#11
Federico Carlos Blanco, Marcelo Abel Soria, Laura Inés Klepp, Fabiana Bigi
Bovine tuberculosis (bTB) is a zoonotic disease caused by Mycobacterium bovis that is responsible for significant economic losses worldwide. In spite of its relevance, the limited knowledge about the host immune responses that provide effective protection against the disease has long hampered the development of an effective vaccine. The identification of host proteins with an expression that correlates with protection against bTB would contribute to the understanding of the cattle defence mechanisms against M...
September 14, 2017: Journal of Molecular Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28893919/antigen-localisation-influences-the-magnitude-and-kinetics-of-the-endogenous-adaptive-immune-response-to-recombinant-salmonella-vaccines
#12
Yanina R Sevastsyanovich, David R Withers, Claire L Marriott, Faye C Morris, Timothy J Wells, Douglas F Browning, Irene Beriotto, Ewan Ross, Hossam Omar Ali, Catherine A Wardius, Adam F Cunningham, Ian R Henderson, Amanda E Rossiter
The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy to present heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ in where heterologous antigens are expressed and localised within the bacterium and it is unclear how antigen localisation modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in the cell culture supernatant...
September 11, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28889065/profiling-dendritic-cell-subsets-in-the-patients-with-active-pulmonary-tuberculosis
#13
Yuan-Bin Lu, De-Qian Xiao, Kui-Di Liang, Jun-Ai Zhang, Wan-Dang Wang, Shi-Yan Yu, Bi-Ying Zheng, Yu-Chi Gao, You-Chao Dai, Yan Jia, Chen Chen, Ze-Gang Zhuang, Xin Wang, Xiao-Xia Fu, Yong Zhou, Jixin Zhong, Zheng W Chen, Jun-Fa Xu
Dendritic cell (DC) plays an important role in the immune response against pulmonary tuberculosis. However, the phenotypic profile of DC subsets in peripheral blood in individuals with active pulmonary tuberculosis (APT) is still inconclusive. Here, we demonstrated that the absolute numbers of total DC (tDC), myeloid DC (mDC) and plasmacytoid DC (pDC) in individuals with APT were decreased compared to healthy controls (HCs). The decreased number of DCs, especially of pDC, seems to be a useful diagnostic marker of APT...
September 7, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28887521/sex-differences-in-the-c57bl-6-model-of-mycobacterium-tuberculosis-infection
#14
Jannike Dibbern, Lars Eggers, Bianca E Schneider
Globally, tuberculosis (Tb) notification data show a male-to-female ratio of 1.7 and higher, but the underlying reasons for the male bias remain elusive. Despite the well-known gender bias in human pulmonary Tb, a majority of experimental animal studies either do not separate and analyze data by sex or do not report the sex of their subjects at all. In the present study, we report increased male susceptibility in one of the most commonly used mouse models for Tb, C57BL/6 mice. Our study revealed that disease progression upon aerosol infection with Mycobacterium tuberculosis (Mtb) was accelerated in males resulting in increased morbidity and mortality compared to females...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28886145/application-of-a-whole-blood-mycobacterial-growth-inhibition-assay-to-study-immunity-against-mycobacterium-tuberculosis-in-a-high-tuberculosis-burden-population
#15
Richard Baguma, Adam Penn-Nicholson, Erica Smit, Mzwandile Erasmus, Jonathan Day, Lebohang Makhethe, Marwou de Kock, E Jane Hughes, Michele van Rooyen, Bernadette Pienaar, Lynnett Stone, Willem Hanekom, Michael J Brennan, Robert S Wallis, Mark Hatherill, Thomas J Scriba
The determinants of immunological protection against Mycobacterium tuberculosis (M.tb) infection in humans are not known. Mycobacterial growth inhibition assays have potential utility as in vitro surrogates of in vivo immunological control of M.tb. We evaluated a whole blood growth inhibition assay in a setting with high burden of TB and aimed to identify immune responses that correlate with control of mycobacterial growth. We hypothesized that individuals with underlying M.tb infection will exhibit greater M...
2017: PloS One
https://www.readbyqxmd.com/read/28884285/immune-tb-antibody-phage-display-library-as-a-tool-to-study-b-cell-immunity-in-tb-infections
#16
Nurul Hamizah Hamidon, Siti Suraiya, Maria E Sarmiento, Armando Acosta, Mohd Nor Norazmi, Theam Soon Lim
B cells and in particular antibodies has always played second fiddle to cellular immunity in regard to tuberculosis (TB). However, recent studies has helped position humoral immunity especially antibodies back into the foray in relation to TB immunity. Therefore, the ability to correlate the natural antibody responses of infected individuals toward TB antigens would help strengthen this concept. Phage display is an intriguing approach that can be utilized to study antibody-mediated responses against a particular infection via harvesting the B cell repertoire from infected individuals...
September 7, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28882103/low-serum-vitamin-d-levels-in-type-2-diabetes-patients-are-associated-with-decreased-mycobacterial-activity
#17
María Teresa Herrera, Yolanda Gonzalez, Fernando Hernández-Sánchez, Guadalupe Fabián-San Miguel, Martha Torres
BACKGROUND: Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide. Patients with diabetes mellitus have a high risk of tuberculosis, which may be mediated by an abnormal innate immune response due to hyperglycaemia or low vitamin D levels. METHODS: In the present study, we evaluated inactive vitamin D serum levels and the monocyte response to infection with M. tuberculosis, including phagocytosis of M. tuberculosis, antimycobacterial activity, LL-37, human β defensin-2 and IL-10 gene expression and nitric oxide production, between type 2 diabetes mellitus patients (n = 51) and healthy volunteers (n = 38)...
September 7, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28880895/lag-3-potentiates-the-survival-of-mycobacterium-tuberculosis-in-host-phagocytes-by-modulating-mitochondrial-signaling-in-an-in-vitro-granuloma-model
#18
Bonnie L Phillips, Uma S Gautam, Allison N Bucsan, Taylor W Foreman, Nadia A Golden, Tianhua Niu, Deepak Kaushal, Smriti Mehra
CD4+ T-cell mediated Th1 immune responses are critical for immunity to TB. The immunomodulatory protein, lymphocyte activation gene-3 (LAG-3) decreases Th1-type immune responses in T-cells. LAG-3 expression is significantly induced in the lungs of macaques with active TB and correlates with increased bacterial burden. Overproduction of LAG-3 can greatly diminish responses and could lead to uncontrolled Mtb replication. To assess the effect of LAG-3 on the progression of Mtb infection, we developed a co-culture system wherein blood-derived macrophages are infected with Mtb and supplemented with macaque blood or lung derived CD4+ T-cells...
2017: PloS One
https://www.readbyqxmd.com/read/28877954/suppression-of-toll-like-receptor-2-mediated-proinflammatory-responses-by-mycobacterium-tuberculosis-protein-rv3529c
#19
Upasana Bandyopadhyay, Attinder Chadha, Priya Gupta, Brijendra Tiwari, Kausik Bhattacharyya, Sonam Popli, Rajagopal Raman, Vani Brahamachari, Yogendra Singh, Pawan Malhotra, Krishnamurthy Natarajan
Microorganisms are known to devise various strategies to thwart protective responses by the host. One such strategy is to incorporate sequences and domains in their genes/proteins that have similarity to various domains of the host proteins. In this study, we report that Mycobacterium tuberculosis protein Rv3529c exhibits significant similarity to the death domain of the TLR pathway adaptor protein MyD88. Incubation of macrophages with Rv3529c specifically inhibited TLR2-mediated proinflammatory responses. This included attenuated oxidative burst, reduced phosphorylation of MAPK-ERK, reduced activation of transcription factor NF-κB and reduced secretion of proinflammatory cytokines IFN-γ, IL-6, and IL-17A with a concomitant increased secretion of suppressor cytokines IL-10 and TGF-β...
September 6, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28877927/protective-vaccine-efficacy-of-the-complete-form-of-ppe39-protein-from-mycobacterium-tuberculosis-beijing-k-strain-in-mice
#20
Ahreum Kim, Yun-Gyoung Hur, Sunwha Gu, Sang-Nae Cho
The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin, or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tb-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides...
September 6, 2017: Clinical and Vaccine Immunology: CVI
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