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Tuberculosis and immune response

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https://www.readbyqxmd.com/read/28209712/mycobacterium-tuberculosis-esxl-inhibit-mhc-ii-expression-by-promoting-hypermethylation-in-class-ii-transactivator-loci-in-macrophages
#1
Srabasti Sengupta, Saba Naz, Ishani Das, Abdul Ahad, Avinash Padhi, Sumanta Naik, Geetanjali Ganguli, Kaliprasad Patnaik, Sunil Kumar Raghav, Vinay Nandicoori, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) is known to modulate the host immune responses to facilitate its persistence inside the host cells. One of the key mechanisms includes repression of class-II transactivator (CIITA) and MHC-II expression in infected macrophages. However, the precise mechanism of CIITA and MHC-II down-regulation is not well studied. Mtb 6-kDa early secretory antigenic target (ESAT-6) is a known potent virulence and antigenic determinant. Mtb genome encodes 23 such ESAT-6 family proteins. We herein report that Mtb and M...
February 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28209523/tb-iris-proteomic-analysis-of-in-vitro-pbmc-responses-to-mycobacterium-tuberculosis-and-response-modulation-by-dexamethasone
#2
Liam Bell, Janique M Peyper, Shaun Garnett, Rabecca Tadokera, Robert Wilkinson, Graeme Meintjes, Jonathan M Blackburn
Paradoxical tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) occurs in 8-54% of South African patients undergoing treatment for tuberculosis/human immunodeficiency virus co-infection. Improved TB-IRIS molecular pathogenesis understanding would enhance risk stratification, diagnosis, prognostication, and treatment. We assessed how TB-IRIS status and dexamethasone influence leukocyte proteomic responses to Mycobacterium tuberculosis (Mtb). Patient blood was obtained three weeks post-anti-retroviral therapy initiation...
February 13, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28206982/biocompatible-chitosan-nanoparticles-as-an-efficient-delivery-vehicle-for-mycobacterium-tuberculosis-lipids-to-induce-potent-cytokines-and-antibody-response-through-activation-of-%C3%AE-%C3%AE-t-cells-in-mice
#3
Ishani Das, Avinash Padhi, Sitabja Mukherjee, Debi Dash, Santosh Kar, Avinash Sonawane
Activation of cell mediated and humoral immune responses to Mycobacterium tuberculosis (Mtb) are critical for protection and that nanoparticles mediated delivery of antigens are more potent in inducing different immune responses. Herein, we show that mice immunized with Mtb lipid bound chitosan nanoparticles(NPs) induce secretion of prominent type 1 T helper (Th1) and type 2 T helper (Th2) cytokines in lymph node and spleen cells, and also induced significantly higher levels of IgG, IgG1, IgG2 and IgM in comparison to control mice...
February 16, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28203237/activation-of-the-wnt-pathway-by-mycobacterium-tuberculosis-a-wnt-wnt-situation
#4
REVIEW
Tomás Villaseñor, Edgardo Madrid-Paulino, Rafael Maldonado-Bravo, Antonio Urbán-Aragón, Leonor Pérez-Martínez, Gustavo Pedraza-Alva
Mycobacterium tuberculosis (M. tuberculosis), an intracellular pathogenic Gram-positive bacterium, is the cause of tuberculosis (TB), a major worldwide human infectious disease. The innate immune system is the first host defense against M. tuberculosis. The recognition of this pathogen is mediated by several classes of pattern recognition receptors expressed on the host innate immune cells, including Toll-like receptors, Nod-like receptors, and C-type lectin receptors like Dectin-1, the Mannose receptor, and DC-SIGN...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28199374/a-novel-mycobacterial-in-vitro-infection-assay-identifies-differences-of-induced-macrophage-apoptosis-between-cd4-and-cd8-t-cells
#5
Vanesa Nkwouano, Sven Witkowski, Nidja Rehberg, Rainer Kalscheuer, Norman Nausch, Ertan Mayatepek, Marc Jacobsen
Macrophages are natural host cells for pathogenic mycobacteria, like Mycobacterium tuberculosis (M.tb). Immune surveillance by T cells and interaction with M.tb infected macrophages is crucial for protection against M.tb reactivation and development of active tuberculosis. Several factors play a role in the control of M.tb infection but reliable biomarkers remain elusive. One major obstacle is the absence of functional in vitro assays which allow concomitant determination of i) mycobacterial eradication; ii) cytotoxic effects on host macrophages; and iii) effector T-cell functions...
2017: PloS One
https://www.readbyqxmd.com/read/28196762/enteric-helminth-induced-type-i-interferon-signalling-protects-against-pulmonary-virus-infection-through-interaction-with-the-microbiota
#6
Amanda J McFarlane, Henry J McSorley, Donald J Davidson, Paul M Fitch, Claire Errington, Karen J Mackenzie, Eva S Gollwitzer, Chris J C Johnston, Andrew S MacDonald, Michael R Edwards, Nicola L Harris, Benjamin J Marsland, Rick M Maizels, Jürgen Schwarze
BACKGROUND: Helminth parasites have been reported to have beneficial immune modulatory effects in allergic and autoimmune conditions and detrimental consequences in tuberculosis and some viral infections. Their role in co-infection with respiratory viruses is not clear. OBJECTIVE: Here, we investigated the effects of strictly enteric helminth infection with Heligmosomoides polygyrus on respiratory syncytial virus (RSV) infection in a mouse model. METHODS: A murine helminth/ RSV co-infection model was developed...
February 11, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28194371/non-tuberculous-mycobacteria-in-south-african-wildlife-neglected-pathogens-and-potential-impediments-for-bovine-tuberculosis-diagnosis
#7
Nomakorinte Gcebe, Tiny M Hlokwe
Non-tuberculous mycobacteria (NTM) are not only emerging and opportunistic pathogens of both humans and animals, but from a veterinary point of view some species induce cross-reactive immune responses that hamper the diagnosis of bovine tuberculosis (bTB) in both livestock and wildlife. Little information is available about NTM species circulating in wildlife species of South Africa. In this study, we determined the diversity of NTM isolated from wildlife species from South Africa as well as Botswana. Thirty known NTM species and subspecies, as well as unidentified NTM, and NTM closely related to Mycobacterium goodii/Mycobacterium smegmatis were identified from 102 isolates cultured between the years 1998 and 2010, using a combination of molecular assays viz PCR and sequencing of different Mycobacterial house-keeping genes as well as single nucleotide polymorphism (SNP) analysis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28193909/rv2299c-a-novel-dendritic-cell-activating-antigen-of-mycobacterium-tuberculosis-fused-esat-6-subunit-vaccine-confers-improved-and-durable-protection-against-the-hypervirulent-strain-hn878-in-mice
#8
Han-Gyu Choi, Seunga Choi, Yong Woo Back, Seungwha Paik, Hye-Soo Park, Woo Sik Kim, Hongmin Kim, Seung Bin Cha, Chul Hee Choi, Sung Jae Shin, Hwa-Jung Kim
Understanding functional interactions between DCs and antigens is necessary for achieving an optimal and desired immune response during vaccine development. Here, we identified and characterized protein Rv2299c (heat-shock protein 90 family), which effectively induced DC maturation. The Rv2299c-maturated DCs showed increased expression of surface molecules and production of proinflammatory cytokines. Rv2299c induced these effects by binding to TLR4 and stimulating the downstream MyD88-, MAPK- and NF-κB-dependent signaling pathways...
February 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/28193504/strong-anti-epstein-barr-virus-ebv-or-cytomegalovirus-cmv-cellular-immune-responses-predict-survival-and-a-favourable-response-to-anti-tuberculosis-therapy
#9
REVIEW
Tumaini Nagu, Said Aboud, Martin Rao, Mecky Matee, Rebecca Axelsson, Davide Valentini, Ferdinand Mugusi, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Intact immune responses to cytomegalovirus (CMV) and Epstein-Barr virus (EBV) represent a biologically and clinically relevant correlate of 'immunological fitness' in humans. However, there is a lack of knowledge concerning anti-EBV or anti-CMV responses in patients with pulmonary tuberculosis (TB), in whom aberrant immune responses may promote progression of clinical disease. METHODS: Venous blood samples were obtained from at the time of (sputum smear positive) pulmonary TB diagnosis...
February 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28192437/species-dependent-impact-of-helminth-derived-antigens-on-human-macrophages-infected-with-mycobacterium-tuberculosis-direct-effect-on-the-innate-anti-mycobacterial-response
#10
Naomi Aira, Anna-Maria Andersson, Susmita K Singh, Derek M McKay, Robert Blomgran
BACKGROUND: In countries with a high prevalence of tuberculosis there is high coincident of helminth infections that might worsen disease outcome. While Mycobacterium tuberculosis (Mtb) gives rise to a pro-inflammatory Th1 response, a Th2 response is typical of helminth infections. A strong Th2 response has been associated with decreased protection against tuberculosis. PRINCIPAL FINDINGS: We investigated the direct effect of helminth-derived antigens on human macrophages, hypothesizing that helminths would render macrophages less capable of controlling Mtb...
February 13, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28192214/immune-recognition-surface-construction-of-mycobacterium-tuberculosis-epitope-specific-antibody-responses-in-tuberculosis-patients-identified-by-peptide-microarrays
#11
REVIEW
Davide Valentini, Martin Rao, Giovanni Ferrara, Marc Perkins, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Understanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens. METHODS: We used a HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis (M. tb) to gauge specific IgG antibody responses in sera of TB patients from Africa and South America...
February 9, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28183185/rational-design-of-selective-and-bioactive-inhibitors-of-the-mycobacterium-tuberculosis-proteasome
#12
Kyle A Totaro, Dominik Barthelme, Peter T Simpson, Xiuju Jiang, Gang Lin, Carl F Nathan, Robert T Sauer, Jason K Sello
The 20S core particle of the proteasome in Mycobacterium tuberculosis (Mtb) is a promising, yet unconventional, drug target. This multimeric peptidase is not essential, yet degrades proteins that have become damaged and toxic via reactions with nitric oxide (and/or the associated reactive nitrogen intermediates) produced during the host immune response. Proteasome inhibitors could render Mtb susceptible to the immune system, but they would only be therapeutically viable if they do not inhibit the essential 20S counterpart in humans...
February 10, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28178208/effector-mechanisms-of-neutrophils-within-the-innate-immune-system-in-response-to-mycobacterium-tuberculosis-infection
#13
REVIEW
Eric Warren, Garrett Teskey, Vishwanath Venketaraman
Neutrophils have a significant yet controversial role in the innate immune response to Mycobacterium tuberculosis (M. tb) infection, which is not yet fully understood. In addition to neutrophils' well-known effector mechanisms, they may also help control infection of M. tb through the formation of neutrophil extracellular traps (NETs), which are thought to further promote the killing of M. tb by resident alveolar macrophages. Cytokines such as IFN-γ have now been shown to serve an immunomodulatory role in neutrophil functioning in conjunction to its pro-inflammatory function...
February 7, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28177961/new-concepts-in-understanding-latent-tuberculosis
#14
Claire E Dodd, Larry S Schlesinger
PURPOSE OF REVIEW: Mycobacterium tuberculosis (M.tb), the etiologic agent of tuberculosis, is a prominent global health threat because of the enormous reservoir of subclinical latent tuberculosis infection (LTBI). Current diagnostic approaches are limited in their ability to predict reactivation risk and LTBI is recalcitrant to antibiotic treatment. The present review summarizes recent advances in our ability to detect, treat and model LTBI as well as our understanding of bacterial physiology during latency...
February 7, 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/28177046/stable-expression-of-mycobacterium-bovis-antigen-85b-in-auxotrophic-m-bovis-bacillus-calmette-gu%C3%A3-rin
#15
Caroline Rizzi, Ana Carolina Peiter, Thaís Larré Oliveira, Amilton Clair Pinto Seixas, Karen Silva Leal, Daiane Drawanz Hartwig, Fabiana Kommling Seixas, Sibele Borsuk, Odir Antônio Dellagostin
BACKGROUND: Bovine tuberculosis (TB) is a zoonotic disease caused by Mycobacterium bovis, responsible for causing major losses in livestock. A cost effective alternative to control the disease could be herd vaccination. The bacillus Calmette-Guérin (BCG) vaccine has a limited efficacy against bovine TB, but can improved by over-expression of protective antigens. The M. bovis antigen 85B demonstrates ability to induce protective immune response against bovine TB in animal models. However, current systems for the construction of recombinant BCG expressing multiple copies of the gene result in strains of low genetic stability that rapidly lose the plasmid in vivo...
February 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28176867/primary-macrophages-and-j774-cells-respond-differently-to-infection-with-mycobacterium-tuberculosis
#16
Nuria Andreu, Jody Phelan, Paola F de Sessions, Jacqueline M Cliff, Taane G Clark, Martin L Hibberd
Macrophages play an essential role in the early immune response to Mycobacterium tuberculosis and are the cell type preferentially infected in vivo. Primary macrophages and macrophage-like cell lines are commonly used as infection models, although the physiological relevance of cell lines, particularly for host-pathogen interaction studies, is debatable. Here we use high-throughput RNA-sequencing to analyse transcriptome dynamics of two macrophage models in response to M. tuberculosis infection. Specifically, we study the early response of bone marrow-derived mouse macrophages and cell line J774 to infection with live and γ-irradiated (killed) M...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28168855/vaccination-of-calves-with-mycobacterium-bovis-bacillus-calmette-guerin-reduces-the-frequency-and-severity-of-lesions-of-bovine-tuberculosis-under-a-natural-transmission-setting-in-ethiopia
#17
G Ameni, K Tafess, A Zewde, T Eguale, M Tilahun, T Hailu, A Sirak, F J Salguero, S Berg, A Aseffa, R G Hewinson, H M Vordermeier
Bovine tuberculosis (bTB) is highly prevalent in intensive dairy farms of the urban "milk-sheds" in Ethiopia, and vaccination could be a cost-effective disease control strategy. In the present study, the efficacy of Bacillus Calmette-Guerin (BCG) to protect against bTB was assessed in Holstein-Friesian calves in a natural transmission setting. Twenty-three 2-week-old calves were subcutaneously vaccinated with BCG Danish SSI strain 1331, and matched 26 calves were injected with placebo. Six weeks later, calves were introduced into a herd of M...
February 6, 2017: Transboundary and Emerging Diseases
https://www.readbyqxmd.com/read/28163164/anti-pd-1-pd-l1-therapy-for-infectious-diseases-learning-from-the-cancer-paradigm
#18
REVIEW
Martin Rao, Davide Valentini, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
OBJECTIVES: Immune checkpoint pathways regulate optimal host immune responses against transformed cells, induce immunological memory, and limit tissue pathology. Conversely, aberrant immune checkpoint activity signifies a poor prognosis in cancer and infectious diseases. Host-directed therapy (HDT) via immune checkpoint blockade has revolutionized cancer treatment with therapeutic implications for chronic infections, thus laying the foundation for this review. METHODS: Online literature searches were performed via PubMed, PubMed Central, and Google using the keywords "immune checkpoint inhibition"; "host-directed therapy"; "T cell exhaustion"; "cancer immunotherapy"; "anti-PD-1 therapy"; "anti-PD-L1 therapy"; "chronic infections"; "antigen-specific cells"; "tuberculosis"; "malaria"; "viral infections"; "human immunodeficiency virus"; "hepatitis B virus"; "hepatitis C virus"; "cytomegalovirus" and "Epstein-Barr virus"...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28161464/mycobacterium-tuberculosis-proteins-involved-in-cell-wall-lipid-biosynthesis-improve-bcg-vaccine-efficacy-in-a-murine-tb-model
#19
REVIEW
Martin Rao, Nathalie Cadieux, Megan Fitzpatrick, Steven Reed, Sergei Arsenian, Davide Valentini, Shreemanta Parida, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
OBJECTIVES: Advances in tuberculosis (TB) vaccine development are urgently required to enhance global disease management. We evaluated the potential of Mycobacterium tuberculosis (M. tb)-derived protein antigens Rv0447c, Rv2957 and Rv2958c to boost BCG vaccine efficacy in the presence or absence of glucopyranosyl lipid adjuvant formulated in a stable emulsion (GLA-SE) adjuvant. METHODS: Mice received the BCG vaccine, followed by Rv0447c, Rv2957 and Rv2958c protein boosting with or without GLA-SE adjuvant 3 and 6 weeks later...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28161459/peptide-microarray-based-characterization-of-antibody-responses-to-host-proteins-after-bacille-calmette-gu%C3%A3-rin-vaccination
#20
REVIEW
Davide Valentini, Martin Rao, Lalit Rane, Sayma Rahman, Rebecca Axelsson-Robertson, Rainer Heuchel, Matthias Löhr, Daniel Hoft, Susanna Brighenti, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Bacille Calmette-Guérin (BCG) is the world's most widely distributed vaccine, used against tuberculosis (TB), in cancer immunotherapy, and in autoimmune diseases due to its immunomodulatory properties. To date, the effect of BCG vaccination on antibody responses to host proteins has not been reported. High-content peptide microarrays (HCPM) offer a unique opportunity to gauge specific humoral immune responses. METHODS: The sera of BCG-vaccinated healthy adults were tested on a human HCPM platform (4953 randomly selected epitopes of human proteins) to detect specific immunoglobulin gamma (IgG) responses...
February 2, 2017: International Journal of Infectious Diseases: IJID
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